A Survivor's Guide to Surgical Menopause

Welcome!

2021-09-10T13:16:00.000-06:00

Welcome to our guide for surviving surgical menopause. Congratulations for setting out to learn more about your body and needs in this challenging time!

Because this site uses blogging software, this home page can be a little confusing and, frankly, isn't the best of places to begin reading. Instead, we suggest you begin by reading the "Introduction" tab above, and then move along to the "Table of Contents" page. Working from that to read one article after another in that order will make a great deal more sense for you. And don't forget, if you're looking for something specific, that there's a search field in the left side of the upper pink navbar. Still can't find what you need? Come join us on our forums and we'll try to help you out.

Oxybutynin: a new addition to drugs effective for hot flash suppression

2018-12-10T15:49:00.001-07:00

Research announced at the 2018 San Antonio Breast Cancer Symposium has demonstrated that oxybutynin is more effective in suppressing hot flashes than the current drugs of choice, venlafaxine or citalopram.

"We have to be cautious, as these are cross-trial comparisons, but oxybutynin shows a more significant decrease in hot flash score [than anything else so far], so with the results of this particular study, we will be more keen on using oxybutynin now," he said. (source)

In more detail, researchers tested both doses of oxybutynin, 2.5 mg and 5 mg, and found:

measures related to sleep, leisure activities, work, and relationships, were significantly better in comparison with women who received placebo.

However, neither dosage of oxybutynin offset the effect that hot flushes had on patients' ability to concentrate or on their sexuality. At the lower dosage, oxybutynin did not improve mood or enjoyment of life; at the higher dosage, improvements were seen for these measures. (source)

But as we all know, there is no such thing as a free lunch.

Side effects were as expected with any anticholinergic and included dry mouth, abdominal pain, and difficulty urinating with both dosages.

At the higher dosage, oxybutynin also increased the risk of developing dry eyes, as well as risk for episodes of confusion, diarrhea, and headaches. (source)

Here are the FDA product information files for the 5 mg dose strength. The product is also available in extended release and syrup forms with a total FDA listing here.

As this is posted, drug coupon source GoodRx lists a retail cost of $42.09 for 60 5 mg tablets, but offers coupons to bring that cost down $20-25. Insurance coverage will depend upon individual companies' policies and agreements with pharmacies and manufacturers.

In addition to women with hormone-receptor-positive cancers, especially those taking tamoxifen which contraindicates the use of many SSRIs, this product may be helpful for other women, such as endo sufferers, who are looking for non-hormonal control of their symptoms.

Bijuva: a new combination HRT

2018-10-30T14:02:00.001-06:00

Approval of a "new" hrt made some press headlines for Bijuva. There is not yet a label available (update: see below) from the FDA, but the Reuters press release describes it as

an oral softgel capsule containing a combination of artificial hormones chemically identical to human female sex hormones estradiol and progesterone.

Other press sources are calling it things like "the first and only FDA-approved bio-identical* hormone therapy," which is perhaps stretching things just a bit by implication. It seems to be simply human-identical estradiol and human-identical progesterone in one pill, with the dose it contains identified in releases as 1 mg/100 mg. The "artificial hormones" aspect is simply an overly precise way of stating that they are produced in the laboratory, as is the case with all human-identical hrts, instead of being refined from animal sources, as Premarin is, to produce synthetic or non-human-identical hormonal agents.

So that means that this new pill (which could be expensive because it's new) contains the same things as a generic Estrace 1 mg, one of the cheapest hrts around, plus a 100 mg capsule of Prometrium, also an older formulation. The "new" about this is simply the combination, not actually the fact that FDA-approved human-identical hrts are available in oral dose form.

It's also worth noting that the name, Bijuva, is quite similar in sound to the now-discontinued hrt, Enjuvia. Bijuva is not a replacement for Enjuvia: it contains entirely different hormonal formulations.

So is this a real improvement? If this is the precise dose that any given woman needs and if she finds that the convenience of taking one pill rather than two is worth paying for, then yes, it might be. If her insurance company cuts a deal with the manufacturer or supplier such that they can beat the price of that same supplier for the two separate hrts, she may not have a choice. But for a woman who is in the early stages of working out her needs or who hopes to customize her dose, it could be less suitable because she is locked into just those two doses.

Unlike progesterone-only gelcaps which can be used vaginally, this hrt would not be suitable for vaginal use because of the high dose of estrogen it contains (read more about why taking systemic doses of the active estrogen via pelvic circulation delivery is not necessarily the best idea ever).

And, like all oral hrts, it would provide delivery-related effects that may not be the best option for some women.

The press releases suggest that this new formulation will come on the market in late 2019. We'll keep an eye out and update this and our combination hrts listing page once the FDA releases the full packaging information for it.

Update: Here's the full FDA product sheet for Bijuva.

Hot weather and your HRT

2018-08-09T16:44:00.003-06:00

While questions about HRTS and hot temperatures have come up before, increasingly disastrous summer weather all around the world has really made this topic gain more urgent attention.

There are two aspects to this issue: transporting/storing hrts and using them, and both are affected by heat and humidity.

HRTs and heat

All hrts are affected by temperature and humidity to some degree.

That is the notional reason why hrts have expiration dates (although that period may also be affected by marketing and sales). Further, pharmaceutical manufacturers only guarantee their products' effectiveness within the range of 68-77F (20-25C) although pharmacists tend to support the broader range of 58-86F (14.4-30C) as non-damaging.

Estrogen itself may lose potency when heated, although it's difficult to find specific references that detail this process and much of it is cloaked in spurious dietary advice. Nonetheless, it's a complex molecule and it only works when undamaged.

Irrespective of whatever happens to the estrogen molecule itself with heat, though, other aspects of specific hrt deliveries can definitely be adversely affected by heat.

Oral tablets, whether meant to be swallowed or used transbuccally, will lose more potency over time at high temperatures than cool ones. High humidity getting into pill bottles may also cause tablets to crumble or capsules to stick together and break when attempts are made to separate them. This can affect dose strength and thus how our needs are covered by our usual dose.

Creams may melt and separate in the heat. Sure, you can stir them back together, but that's still iffy in terms of the exact distribution of the active ingredient through the vehicle. Gels may be less well--absorbed if their alcohol-based vehicle evaporates so quickly in the heat that we can't spread them to the required area size, and they may become more concentrated as alcohol evaporates out of the container. Sprays and lotions are liable to suffer similar effects that can change potency of a dose, whether by affecting dilution or application.

Over the years, we've heard of a number issues to do with patches and heat. A common one is the effect heat can have on the adhesive, which is necessary for the delivery of the estrogen the patch contains. Patch brands that previous adhered fine may no longer stick for the full dose period or may no longer adhere fully.

Where HRTs run into heat (and cold) problems

Let's segue from patch adhesion concerns due to adhesive damage into the other issue to do with using hrts in the heat: our bodies. There are two things going on here.

First, there's sweat. Even an otherwise fully adhesive patch may falter when placed on sweaty skin. Similarly, sweat may dilute other transdermals like creams, gels, or sprays, changing the spread area and uptake speed.

Beyond that, though, heavy sweat after application can cause a patch to lift. It can also wash away (or transfer to others) estrogens cached on top of the skin, such as those applied by gel or spray. Only oil-based creams penetrate the skin fully at time of application and are not affected by later sweating. Now, this obviously may not apply to a light "glow" but when we spend an hour or a day or days and nights pouring sweat, then we're dealing with a substantial possibility.

HRTs in transit and storage

But not all damage to hrts comes while we're applying them. They also have to get into our hands in the first place and then from there into/onto our bodies.

HRTs are shipped from the plant where they are manufactured, stored in a warehouse, redistributed/retransported once or several times by a pharmaceutical chain, and stored in the pharmacy all before they come to us, after which we may carry them around or leave them in our car parked while we carry out other errands. Additionally, if we use a mail-order pharmacy plan, the prescription mailer is stored and handled by a shipping service, spends a day or more being driven around in an open delivery truck, and then spends time in our mailbox, which itself may be outdoors or in a temperature-uncontrolled space. Can you see all of the times and places where your prescription could bake in the heat (or freeze in the cold for winter refills)? Because most hrts don't require refrigeration, they may not be handled in ways that preserve that relatively narrow range of effective temperature. And there's no way for us as customers to know that these things may have happened.

And of course, once we do get them home, many of us are finding that where historically we didn't need air conditioning to get through summer weather, we're now living in much hotter temperatures. Our homes may spend days or even weeks at the elevated levels that damage hrts.

So what can we do? We have no control over what happens before we're holding our hrts in our hands, and the many commercial interests that control them upstream of us have, at the moment, little incentive or regulatory interest in minimizing damage. Similarly, we've not heard much about insurance refusing to cover replacements of heat-damaged hrts. But as this problem grows, we might expect them to move to protect their profits by making new policies to limit refill coverage. This comes down to fiscal politics, which is rather outside the purview of this website but certainly a concern for many of us in the world we live in.

But once we've got control over our hrt, we can take steps to preserve what potency it might have.

If you're using a mail-order service, is that negotiable with your insurance? Can you document heat damage (photos are your friend, here) to packaging or mailboxes in the hot sun? Can you arrange quicker pickup of the mail or move the mailbox to a shaded location? Sometimes once we figure out where problems can occur, we can take steps to reduce their likelihood.

If you're picking your prescription up from the pharmacy, you may be able to avoid leaving it in a hot locked car while you finish your shopping. Basically, if you wouldn't leave your child or your pet in that locked car, it's also too hot to leave your hrt.

What about at home? To begin with, the bathroom is the worst place in the house to keep your hrt because of all rooms, its the most likely to become even hotter and even more humid as you use it. So yeah, it may be convenient...right up until your hrt doesn't function well enough any more.

Going in the other direction, refrigerators are cooler than the recommended temperatures, so they aren't the best choice either. Still, if we were trying to decide between a 100F+ room and a refrigerator, we'd seal our hrt up well (to prevent moisture damage) and put it in the fridge. If you have a basement, that may be slightly cooler if you have access to a secure location in it. You may need to search to find the coolest place in your home and even then it might not be cool enough. But it's still good to get those hrts out of the bathroom.

Obviously, if you have air conditioning that's going to help a lot. But many of us don't have the money or even the time to put this in place, especially if we don't own where we live. In a pinch, there are a number of clever cooler concepts that have been developed for third world countries that can be adopted to create small, custom coolers or to cool the air without electrical appliances (1, 2, 3).

HRTs in use in the heat

It seems obvious that we should do what we can to keep our use of hrts as unaffected by the heat as possible. But when our bathroom is roughly the temperature of the surface of the sun, it may be difficult to actually dry our skin off enough to apply an hrt. Additionally, because our pores are open and blood vessels close to the skin are dilated to the max to try to dump excess body heat, our bodies may take up our hrts much faster than in cooler weather. Both of these things may affect how we feel on our hrts.

What to do? Once we're aware of the issue, we need to do some personal troubleshooting. Is there a (slightly) cooler part of the house we could go to and cool down a bit before applying our hrt? Can we stand in front of a fan until our temperature normalizes a bit? Should we even go so far as to switch the time of day of taking our hrt, even knowing that this might put us in conflict with our natural biorhythm of higher estrogen levels in the morning? Do we need to take special precautions around kids or pets to avoid sweating some of our hrt onto them? All of these will require personal answers and troubleshooting, but they're things to consider. The inconvenience of changing our routines for hot weather (and then remembering to actually do them!) may well be offset by not having to endure hormonal instability. Overheating is annoying enough without adding hot flashes and mood instability from fluctuating estrogen.

Beyond keeping things cool, sealing pills or sprays in a plastic bag might help protect them, a bit, from either humidity (pills) or excess evaporation (spray canister).

How will you know if your HRTs are heat-damaged?

Well, some signs are obvious. If you open your mailbox and find a stained parcel or the hrt packaging itself shows signs of leakage, taking a photo and then taking steps to return that hrt is a good place to start.

But mostly, it's not going to be obvious. It's more likely to show up in how our hrt works for us. If we've been stable on this hrt at this dose for a time and suddenly things are falling apart, it's not that our hrt has "stopped working" or some other magical effect has taken place ("jammed receptors" or "needing a hormone holiday" are some of the popular but incorrect mythologies). It may be that our hrt just isn't delivering that dose due to heat damage or heat effects upon delivery. But this is a tricky call, one that takes some thought. Extreme hot weather is a stressor in itself, and we know that stresses, especially ones that linger on for a week, two weeks, or more can also upset our hrt balance. But as we troubleshoot loss of balance in hot weather, we shouldn't forget the heat/hrt damage as one possible cause.

So should we just double up on our hrt in the heat? No, that's likely to be a too-sweeping change. Really, a better first option would be to try to get a replacement refill that hasn't been damaged and to store it as appropriately as we can manage. But if we're stuck with a damaged batch and need to make the best of it we can, it's probably going to be less stressful and more on-target to slowly increase the amount we're using by no more than 10% of a usual dose at a time. That lets us feel our way to "right" rather than risking the even worse discomforts of an excessive dose. And, of course, it's important not to forget to revert to the correct dose again with the next refill. Even if it's still hot? Yes, because we won't know precisely how damaged this one is, and the adjustment for one batch may not at all be the adjustment needed for the next.

Special cases

This also applies to our summer vacations. We may have fine temperature control at home, but how about when we've packed the whole family in the car and headed off to [vacation destination] with our hrt stashed in a suitcase in the trunk? Taking care to keep our hrt within temperature range during travel and at our destination is a annoyance, but also can go a long way towards reducing the risk of losing our hormone balance while we'd rather be having a nice time on vacation.

And one last word on wildfires and other climate disasters. With increasingly extreme heat comes dryness and risk of fires, often in heavily-inhabited areas, or more violent hurricanes affecting areas further inland. The wise thing to do as our climate changes is to have an evacuation plan, if not "go bag" with essentials (this is a basic example of what to include, but an online search will reveal many more articles and lists). While we may not keep our prescriptions in them, having a grab-at-the-last-minute checklist so that we're reminded to take them with us can be essential to our health. Losing a home or being relocated is traumatic enough; in an evacuation scenario, it can be extremely difficult to get needed prescription refills and in some cases, insurance companies may not deem that an adequate justification for them. There are many resources online about how to put together evacuation bags, but for those of us on hrt, that's a critical piece to include.

Plan ahead

No matter where you are in your annual climate cycle, we can look forward to heat, extreme weather, and wildfires becoming the new norm as our planetary atmosphere grows ever warmer and more violent. We all need to be aware of the special vulnerability our HRTs represent and take steps to plan to protect them as much as we can.

The redemption of HRT

2017-07-02T17:25:00.002-06:00

Ding dong! The witch is dead! Or, at least, the witch-hunt over hrts.

The beginning lay, catastrophically, with the cancellation of the Women's Health Initiative Study in 2002. There was a huge worldwide panic in the press, with the end message that using HRTs caused breast cancer. An immediate response followed, in which roughly 50% of the women in the US stopped taking HRT. Over time, attempts were made to suggest other ways of interpreting the data and stances softened, but the basic message persisted: HRT was too dangerous to use.

Whilst HRT supporters continued to explore how hormonal support in menopause, especially surgical menopause, could still be safely used, the costs began to accrue. Studies have suggested that nearly 50,000 women in the US, who were in surgical menopause and quit HRTs because of the study-related panic, died due to that decision.

Further, there were significant fiscal costs both to women and to the general economy from the morbidity due to hot flashes and other untreated menopausal issues. Between 1999 and 2011, says one study:

Women with hot flashes used more healthcare services, particularly outpatient services, than women without symptoms, the researchers found. The extra services added up to $1,336 more per person per year compared to women without symptoms, and the indirect economic loss due to missed work was an extra $770 per woman per year.

Additionally, the authors of that study attributed about $300 million in losses per year to untreated hot flashes, and for the full population of the US, expand that loss estimate to $billions. In Europe, a similar study/estimate suggests a loss of more than €100 million per year just in the Netherlands alone.

But misery isn't measured in currency or even deaths alone. The vast number of women untreated and told to swallow their symptoms because they were "just depressed" or otherwise had failed at talking themselves out of anything more than "a few warm spells" (the classic medical description of menopause presented by many doctors) cannot be counted. But we felt it and we saw it in the discussions online amongst the menopause community, as women struggled to make sense of their symptoms in a climate that forbade them treatment and turned the blame back on themselves. At best, we hoped that with time the more sensible interpretations of the study outcome would take hold and those stances would soften in the decades ahead.

A shocking statement

And that's how things continued until March of 2017. That's when a startling review article was published in Climacteric, the journal of the International Menopause Society, by R.D. Langer, whose background is cited as:

The author was the Principal Investigator for the WHI Vanguard Clinical Center at the University of California, San Diego for the entire primary study period from 1993 through 2005, Chairman of the WHI Principal Investigators Committee from 1994 to 1995, a member of the WHI National Steering Committee from 1994 to 2005, and Chairman of the WHI Observational Study Scientific Advisory Committee from 1996 to 2005.

Here's the full citation:

R. D. Langer (2017): The evidence base for HRT: what can we believe?,
Climacteric, DOI: 10.1080/13697137.2017.1280251 (alternate link)

Basically, the author asserts that many of the research team were shut out of the decision to publish the initial WHI results (which resulted in the study cancellation) paper and were given neither time to review the release nor comment upon it. Further, the timing worked out such that the press release came out before anyone capable of reading the results could have access to them. And, finally, the press release itself was manipulated to emphasize the breast cancer risks...even though they did not exist when the data was correctly analyzed. The author summarizes in terminology rare in the medical press:

The unmistakable and deliberate focus of the small group of self-appointed authors was to trumpet a finding of harm from breast cancer – the science and statistics notwithstanding. This was deeply embedded in the paper and emblazoned in the press release.

The author concludes:

The WHI trials were soundly designed to address the questions the program was intended to answer, with planned procedures duly noted in the protocol. That good science became distorted and ultimately caused substantial and ongoing harm to women for whom appropriate and beneficial treatment was either stopped or never started. Key faults have included: failure to properly identify the study goals and population characteristics in presenting and interpreting the results; inappropriately generalizing the findings to a key sub-group – newly menopausal women – that was not adequately represented; inappropriately generalizing the findings from specific medications to an entire class; failure to put the findings in the context of existing knowledge (taking the position that the prior studies were simply wrong); favoring publicity, fear and sensationalism over science; and departing from protocol – focusing on unadjusted results, while avoiding planned analyses with proper adjustments and better statistical power.

That's pretty powerful stuff, isn't it? Basically, the WHI-mediated panic was an historical blip. But although we saw a followup editorial or two, it certainly escaped notice in the popular press.

Where could we expect to go from there? At the time, in presenting it to our discussion group, we suggested:

As women, we can work to correct the misunderstandings of women and we can bring this review of Langer's to the attention of our doctors when they insist upon the dangers of hrt. It took mere moments for this disaster to unfold upon us women in menopause; it will likely take decades before the damage is undone, especially amongst the doctors who may resist any updating of their opinions.

But then!

Well, as it turns out, we were wrong and we couldn't be happier about that.

Although they released the news on a major US holiday weekend, the North American Menopause Society, one of the most conservative of guideline-publishers and one of the ones to jump most thoroughly on the take-hrt-and-die post-WHI bandwagon, published a new set of menopause treatment guidelines that totally revised their stance on HRT use, even in women with the BRCA mutations and even on use by older women.

Here's an article summarizing the new statement:
Don't Be Nervous About Hormone Therapy for Menopause, Says NAMS (free signup required to read)

And here's The 2017 hormone therapy position statement of The North American Menopause Society in its journal abstract and in full.

What it says

First of all, the position paper states its applicability:

Key to initiating or continuing HT in an individual woman is an understanding of the benefits and risks of age at initiation or time since menopause, specific formulations or types of HT, the duration of therapy, the need for monitoring during therapy, potential risks of continuation, and the need for shared decision making.

The use of HT is considered for different cultural or minority populations of women, including those with surgical menopause, early menopause, or primary ovarian insufficiency (POI) and for women aged older than 65 years.

The paper also cites the scientific foundation for its conclusions:

based on material related to methodology, a review of key studies and evidence-based literature, and presentation and synthesis of evidence. It was written after this extensive review of the pertinent literature and includes key points identified during the review process.

And they provide another whole document of the actual scientific background, should anyone want to consider the basis for their points. This may not mean a lot to you, but it's part of establishing how and why doctors can take faith in this as "evidence-based medicine." In other words, they've got the evidence in spades...or at least 58 pages worth of it.

The statement as a whole is fairly clearly composed and not difficult to read and we encourage women to read it for themselves. There are key points identified and clearly listed out after each section, and we for the most part agree with all of them. Perhaps startlingly, there's very little in there that's actually new or different from our own understanding, carefully sifted from research and consideration and spelled out here on the site.

Amongst the things that did catch our eye, however, was the reference (p6, vasomotor symptoms) to a 300 mg dose of progesterone:

Micronized progesterone 300 mg nightly significantly decreases VMS (hot flashes and night sweats) compared with placebo and improves sleep. Synthetic progestins have also shown benefit in studies. No long-term study results are available.

We're a little wary of that one because of the risk of depression and vertigo with doses like that, not to mention the risk profile suggested in research about breast and cancer risk. For a lot of women, this wouldn't just "improve" sleep; it would be akin to general anesthesia! So we look at the "no long-term study results" as an important flag on this one, not to mention years of women's attempts to follow Dr. John Lee's advice that the more progesterone a woman can take, the better she'll be (spoiler: we have found many women's experiences to disagree strongly with this). In fact, elsewhere in the statement is the concession that high doses of progestins may be associated with depression.

We're pleased to see that in general, NAMS is distinguishing between the effects of oral as opposed to transdermally-delivered HRTs. This is big, not the least of which is because for years Premarin was taken as being synonymous with all HRTs and thus tarred all HRTs with any effect of either its specific formulation or its delivery route.

We're also pleased that this paper recognizes that women who have a hysterectomy with retained ovaries often experience subsequent early menopause:

For women whose ovaries are retained at the time of hysterectomy, there is a two-fold increased risk of ovarian failure, and 20% or more of these women may develop symptoms of diminished ovarian reserve within 1 year

Many women have been denied HRT following a hysterectomy because they nominally still have ovaries. Documenting that those ovaries may experience reduced output can make a great difference for these women. We've known about this statistic for years, but judging by the number of women complaining about this situation, not as many doctors as we might hope do.

And for those who have had an oophorectomy, there is no longer a "wait and see if you need it" (which we've always felt rather meant "demonstrate enough suffering to show you deserve it") aspect. The guidance is clear:

Unless contraindications are present, ET is indicated for women who have had a bilateral oophorectomy and are hypoestrogenic to reduce the risk for VVA and dyspareunia and osteoporosis, with observational data suggesting benefit on atherosclerosis and CVD, and cognitive decline and dementia.

The paper notes that estrogen has been demonstrated to reduce joint pains and stiffness. That's something that women have been told for years was not and could not possibly be related to menopause, leading to lengthy diagnostic journeys through the autoimmune disease realm. Once more, women's experiences are validated here, and that should vastly improve our ability to be successful in advocating for and obtaining appropriate treatment.

Finally, there is a demonstrated improvement in quality of life with HRT that may make the risks of HRT acceptable. What a notion! Women want to feel well and they're willing to accept some risks to do so. Again, this is quite in keeping with what we have seen women pleading for during the whole WHI brownout on HRT.

In the area of osteoporosis, there are no surprises other than the endorsement of HRT for preserving bone density. Of interest, however, is the statement that "Bone protection dissipates rapidly after HT discontinuation, but no rebound in fracture risk has been found." This suggests that when women finally do decide to quit HRT, they aren't going to immediately shatter. That doesn't negate the need for good bone maintenance practices throughout menopause, but it gives some hope that relinquishing HRT doesn't automatically mean going onto a bisphosphonate.

One important area this position paper identifies and begins to clarify is what women with hormone-related cancers should do.

For women with breast cancer, low-dose vaginal estrogen should be considered and prescribed in consultation with their oncologists.

Note that this doesn't default to an OB-GYN or family doctor. This is specialty territory, and so this is where we need to turn to an oncologist. If you've been forbidden HRT because of a vague "family history" of cancer, you deserve a full and detailed workup of your history and actual genetic risks rather than depending upon something Aunt Martha said once. And if you have been treated or are now being treated for breast cancer and are in pain from GSM (formerly known as vaginal atrophy), this holds out considerable hope that you might be able to use this most effective treatment if nonhormonal measures have been unavailing.

With respect to genetic risk for cancer,

Limited observational evidence suggests that HT use does not further increase risk of breast cancer in women with a family history of breast cancer or in women after oophorectomy for BRCA 1 or 2 gene mutation.

But for women who have or who have had breast cancer, the outlook remains unfavorable:

Systemic HT is not recommended for survivors of breast cancer, although selected cases with compelling reasons may be discussed in conjunction with an oncologist after nonhormone options have been unsuccessful.

More detailed analysis of risks involved with lung, colon, and ovarian cancer are in the statement, but women concerned about those areas definitely need to read the statement itself.

And this is the summary given of their overall evaluation and advice:

Hormone therapy formulation, dosing, regimen, route of administration, and the timing of initiation of therapy likely produce different effects, although these have yet to be evaluated in head-to-head RCTs, and there is a significant difference in the benefits and risk of estrogen alone compared with estrogen combined with different progestogens, at least as studied in the WHI. The concept of ‘‘lowest dose for the shortest period of time’’ may be inadequate or even harmful for some women. A more fitting concept is ‘‘appropriate dose, duration, regimen, and route of administration.’’ Given the more favorable safety profile of estrogen alone, longer durations may be more appropriate. Risk stratification by age and time since menopause is recommended. Transdermal or lower doses of HT may decrease risk of VTE and stroke.

We want to underscore this notion of ‘‘appropriate dose, duration, regimen, and route of administration.’’ This pretty much adopts an individualized evaluation of a woman's situation and goals as the standard, rather than an arbitrary "best" HRT or dose or age guideline. This is big. This is great. This is going to take some work within the fundamentally patriarchal field of medicine, but oh, what a wonderful goal.

And who agrees with it?

The new NAMS statement includes a lengthy list of endorsements quoted at the end, and we are copying this out just to demonstrate how widespread this revision of the "party" line now is:

This NAMS position statement has been endorsed by Academy of Women’s Health, American Association of Clinical Endocrinologists, American Association of Nurse Practitioners, American Medical Women’s Association, American Society for Reproductive Medicine, Asociacio´n Mexicana para el Estudio del Climaterio, Association of Reproductive Health Professionals, Australasian Menopause Society, Chinese Menopause Society, Colegio Mexicano de Especialistas en Ginecologia y Obstetricia, Czech Menopause and Andropause Society, Dominican Menopause Society, European Menopause and Andropause Society, German Menopause Society, Groupe d’e´tudes de la me´nopause et du vieillissement Hormonal, HealthyWomen, Indian Menopause Society, International Menopause Society, International Osteoporosis Foundation, International Society for the Study of Women’s Sexual Health, Israeli Menopause Society, Japan Society of Menopause and Women’s Health, Korean Society of Menopause, Menopause Research Society of Singapore, National Association of Nurse Practitioners in Women’s Health, SOBRAC and FEBRASGO, SIGMA Canadian Menopause Society, Societa` Italiana della Menopausa, Society of Obstetricians and Gynaecologists of Canada, South African Menopause Society, Taiwanese Menopause Society, and the Thai Menopause Society. The American College of Obstetricians and Gynecologists supports the value of this clinical document as an educational tool, June 2017. The British Menopause Society supports this Position Statement.

How will this affect me?

If you're already taking HRT, relax. We still have data that suggests that our lowest effective dose still relates to least risks, especially with regard to combined HRT (estrogen + progestogen). But we also know that "lowest" really means the one that makes us feel the way we define "well" in menopause to be. With the new statement, though, we no longer have to fight off our doctor's insistence that we stop HRT after five years of use (a disastrously simplistic reading of the original WHI study cancellation report) or, really, at any particular age milestone. That cap is lifted and it's now supported that we can continue to reap benefits from ongoing HRT use. We'll still argue that we need to reappraise our level of need for supplementation as we age , but that's just housekeeping.

If you quit HRT and are now thinking about going back on it to regain its benefits, sorry. It's still felt that the evidence is strong enough, even for transdermal HRTs, that they raise clotting risk enough that if we have been off of them for any substantial time (something like a matter of months), our risks upon resuming are not adequately offset by benefits. This may be negotiated according to amount of time and the quality and quantity of our symptoms, though, so it's not yet an absolute ban. We may see this thinking revisited in time and we'll let you know if we see anything that changes that position, but for now, "no" seems to be the authoritative word. But even if we've stopped systemic HRT, don't forget that we can continue using vaginal HRT to support those local tissues and functionality without that concern.

If you want to take HRT and your doctor says no, it's too dangerous and gives you cancer, this statement provides your best argument, hot from the medical press and international approval. But remember, our doctors are busy and even if they have time to read journals, this may still be beyond their usual subscription list. So feel free to share the link to the position statement and call attention to the fact that so many international agencies have endorsed it.

And for the sake of all women in menopause, we can bring this up in conversation. While women often conspire in a general silence about menopause (no, we don't know why and it makes no sense, really), so much of the WHI-related anti-HRT panic was passed along woman-to-woman. So now we can reverse this trend by talking with our fellow women when the topic arises and make sure that if they are not comfortable in their menopause, they know about this latest information on HRT and recommendations for its use. We focused so long on its dangers, and that totally caused everyone to lose sight of its benefits. We finally have solid, science-based ground that we can use to help turn that conversation around.

The Cenestin-Enjuvia discontinuation quandary

2017-01-25T13:30:00.001-07:00

Once that these two HRTS were taken off the market, we had an influx of women joining our discussion group asking what they can take to replace them.

That's not an easy question to answer. In part, the answer depends upon just why each woman chose that HRT and continued to take it. So let's look at some of the ways we might end up with this particular blend of conjugated estrogens and consider where we might go from there.

The first one they tried

For women who took one of those brands simply because that's the first one their doctors gave them and it seemed to work okay, this presents an important opportunity to actively choose and try out other hrts. We've put up a simple framework and supporting aids for working through this process based upon each woman's own priorities, not whichever drug rep most recently pitched their product to our doctor. If we work though the selection process, choosing an HRT that meets our own preferences and lifestyle, our doctors should honor that request. And because we've done our homework beforehand, we're prepared to state just why we're making that request, which factors are important to us. We may not have success with our first try or our first try may need a bit of tweaking, but we have to start somewhere. The good news is that this process is easier moving from the stability of a good solid HRT foundation than if we've just had surgery or have been in a state of hormonal uproar.

Alternative to Premarin

If a woman chose this HRT as an alternative to the Premarin that their doctors were urging on them, no, there is not another alternative. There is no other vegetable-source HRT on the market that provides conjugated estrogens. If your doctor's approach to prescribing HRT is Premarin-or-nothing and they will not countenance your using a different type of HRT, the other option is to find a more reasonable doctor who is willing to let you make the critical decisions about your own body and health. Or take Premarin. Even though Premarin is likely to provide for a somewhat different experience, it may work acceptably if one of the others previously did. That assumes, of course, that one is not a vegan or does not have ethical objections to its manufacture.

Tried everything

If women came to this HRT after hopping from one brand and type to another, taking each one at one dose for a short period of time and then, because that one didn't fit, moving on to another, it may be time to reflect upon that process. It often happens that the first dose of an HRT we take doesn't thrill us, but if it does demonstrably deliver to our bodies, we can often tweak the dose or application mode to provide a better fit. When we instead simply jump to another HRT and then another, we pile up the stress of all of those imbalances on top of an already stressful lack of estrogen, leaving us in a deeper and deeper hole we've got to dig back out of.

We've written elsewhere about the process of choosing and tuning an HRT, and while it's not instant gratification, we're all capable of the self-observation skills to carry this out. This may be a good time to revisit this basic selection process, think about which formerly-tried HRT really seemed as though it might have been a good fit for our lifestyle, and revisit it for another attempt. It's very important to remember that if we did this hopping in the first few months after a hyst, we were adding the hugely stressful burden of the menopausal transition to all of the things going on in our bodies, and in a changed setting, months or years later, our overall response might be changed as well.

Prefer oral

If a woman came to this HRT simply because they wanted an oral HRT, a pill they could pop and not worry about it, then reviewing the list of HRTS available in the US (this issue does not affect those using UK HRTs since there was not a non-Premarin conjugated estrogen sold in this market) will show you your options. While this delivery has been less popular in recent years because of its greater risks for cardiovascular disease and cancer, it remains a valid choice for women who are willing to accept that risk profile or who have found that most transdermal deliveries don't work effectively for their bodies.

Uncomfortable with estradiol

While the majority of women today use estradiol HRTs, that contain this active form of estrogen, there is a body of women who find this much activity in a dose excessively stimulating. While we can speculate about genetic variants in metabolism, we don't really have any good, verified explanation why this affects some women but not most others. Nonetheless, after giving more than one estradiol at more than one dose a try, these women just can't settle in. In the end, an HRT that is more estrone-based (the less active, storage form of estrogen) may be more comfortable for them.

Unfortunately, there are not a lot of options for these women. Some of the estrone options will be sold as "piperazine estrone sulfate" (formerly known as estropipate), sold as brand names Ortho-Est and Ogen, or "esterified estrogens", sold as the brand name Menest. It's not clear how many of these remain on the market, but women report they are successful in finding them from time to time. Probably the best tactic, since this availability is not something your doctor will be able to advise you on, is to call around to pharmacies to see if any of them carry or can order it, and if you find one, then ask your doctor to prescribe it for you.

The other option for an estrone-based HRT would be to have one compounded. While compounding pharmacies can make up all-estrone or an estrone-estradiol blend of any proportion for use by a variety of routes (oral, transdermal, transbuccal), women should be aware that the typical pharmacy-blended "bioidentical" prescription is a generic blend that is more appropriate for a woman in natural perimenopause and contains mostly estriol, a weak estrogen breakdown product effective only in urogenital tissues, plus a small amount of estradiol. This particular type of HRT is not likely to meet a woman's needs in surgical menopause. Instead, one needs to have a doctor prescribe either all estrone or a proportional estradiol/estrone blend to come closer to replicating something more like the conjugated estrogens that have been discontinued. Compounding pharmacies cannot make up a conjugated estrogen blend to match the discontinued HRTs because they do not have access to the components.

Prefer a synthetic estrogen

There are many factors that go into selection of HRTs, and some women may for one reason or another choose a non-human-identical estrogen. There is not another synthetic estrogen blend on the market, however. The most popular synthetics that are not Premarin are ethinylestradiol, a potent synthetic used in oral contraceptives, and tibolone, sold as Livial or Tibofem, that is a synthetic steroid drug with some estrogenic, progestogenic and androgenic activity. It is unlikely that either of these will provide for the same experience as the conjugated estrogens.

How to switch

Once you've made your choice, have your new HRT and are about to run out of the last of your Enjuvia or Cenestin, you might be wondering what the best tactic is for changing over. Luckily, it's pretty easy:

Take your last conjugated estrogen pill.
Wait 24 hours.
Begin your new HRT.

It's as easy as that.

Now, because the conjugated estrogens aren't actually human-identical estrogens, it may take your body a while to fully metabolise them, especially if you've been taking them for years. So you may find that after a few days to a few weeks or even possibly a month or two, your new hrt, even if it felt great at the beginning, now doesn't feel as though it's quite such a good fit. Don't panic! This doesn't mean it's stopped working. It just means that you were still cruising on some leftover conjugated estrogens and now they're gone so they're not contributing to your total coverage any longer. And that means that you need to make a small bump in the dose of your new HRT. In this context, "small" generally seems to mean no more than about 10-15% of your dose, not doubling it. Too big a jump is not only uncomfortable in itself, but it risks taking us right past our best dose and into the risky and unpleasant territory of excess. So this is a case where being gentle with ourselves really pays off better in the long run.

One other question we often see has to do with how much of a dose we will need of our new HRT. In general, wherever we were in the range of available doses of our old HRT (highest, lowest, middle), that's where we start in the range of doses of our new HRT. That's just a guess and it won't be perfect, but a guess is as good as we can get when changing from one type of HRT to another. So we start there and then tune. If in doubt, it's almost always better to underestimate than overestimate, just because it's easier to identify and quicker and safer to play catch-up from.

The bottom line

Cenestin and Enjuvia are gone. There is no secret illegal internet pharmacy that can provide non-counterfeit versions of it. There is no immediate replacement that we can expect to work exactly the same way. This means that, one way or another, you're changing HRT.

In order to best do this, you need to identify your own situation and goals, pick a new option, and test it, including tweaking it if needed.

We can help you with this. Here are the links again for some of the specific resources we can provide:

And of course you're always welcome to come to our discussion group to talk through your own process. We can't tell you what will work best for your own body, but we can help you and keep you company as you explore the various options you have.

The "problem" of bioidentical HRTs

2015-12-23T10:14:00.001-07:00

Medical news services are full of articles decrying surveys indicating the popularity of compounded HRTs (one, two). With figures showing use statistics varying from 28-68% of HRT users choosing compounded (so-called "bioidentical") HRTs, this represents a significant loss of income to pharmaceutical companies. Dismay over this loss is cloaked in a variety of concerns, typically that these HRTs are not FDA-approved and that they come without boxed warnings, but the subtext is very clearly "but they didn't get them from US" or even more blatantly "but they didn't do this OUR way." And the tactics suggested in the more instructional of these articles, aimed at physicians, focus primarily upon creating fear and shame in these straying patients.

What seems to be substantially missing from the medical professionals' side of the discussion is any attentiveness to why women have made this decision and how medical practice could address those concerns better. "Personalized" is what a lot of the comments come down to, but that's not the full picture we see in our discussions with women.

Women talk about things like how they're seen as noncompliant when the stock HRT their doctor offers them doesn't suit their needs or even their lifestyle. Women talk about being rebuffed with "I can't help you" or "I don't do that" when they ask for a different HRT brand or route or dose as they struggle to find their way in an opaque and guideless wilderness of choices. Women take articles they've found from medical journals or medical specialty group consensus documents to appointments to discuss latest findings and guidelines and are waved off with "I know everything I need to about HRTs." Women who have had cancers find discussions of their hormone needs flatly dismissed with the notion that it is ungrateful, their lives having been saved from cancer, to want to enjoy those lives with some quality of comfort. Women disabled by symptoms are frightened when those symptoms are waved off with an "I gave you HRT so it can't be your hormones" and the blame turned back on them. Women in surgical menopause, who understand that this is a different entity to natural menopause, are unable to establish trust with health professionals who insist that their symptoms are simply self-indulgence and that "a few warms spells and it'll all be over." And women who have been taught that medicine is strictly evidence-based are dumbfounded to find that there are no tests to guide their way and no objective standards that can be applied beyond "the FDA says this drug works" when a particular HRT manifestly doesn't do so for them.

There is a vast gulf between what doctors want—customers—and what women in menopause want—health—and everything in these "bioidentical HRT" discussions seems to indicate that doctors are not willing to bridge that gap. Is it any wonder, then, that advertising claims of customization, personalized care, attentive adjustment of HRTs, "natural" treatments, and safety—no matter whether justified or not—are winning out with these customers in the face of the "do it our way or no way" approach they feel they are receiving from their medical caregivers?

It can be argued that menopause is really a poor fit for allopathic medicine in the first place, that being, by definition, the diagnosis and treatment of disease. What women in menopause want is not to be labeled with a disease requiring treatment but rather a way to maintain their health in the face of a lifestage change that alters their health, comfort, and risks profile. For all that is good and bad in the compounded HRTs industry (and we have many thoughts on that), that's what is, in the end, the perception of the product being sold. Women are no longer the dependent, easily-influenced, uninformed 50s-era housewives who hang upon their doctors' guidance: they're smart, educated, doing their research, and willing to shop for what they feel they need. And until doctors and other prescribing professionals can address this opportunity in a constructive manner that actually addresses these women's needs, this situation isn't likely to turn around.

In the end, it doesn't matter which HRTs are fully licensed or which of the compounders' claims are bogus. What matters is that those practitioners are saying to women: we hear you; we believe you; we'll work with you. And until medicine can do that, can meet menopausal women from a point of respect, it is likely to continue to hemorrhage patients to more receptive practices.

Vaginal atrophy gains new designation: GSM

2014-08-26T10:07:00.003-06:00

Introducing 'Genitourinary Syndrome of Menopause' (free signup required to read) details a proposed change of terminology from "Atrophic vaginitis" and "Vulvovaginal atrophy."

The change, proposed by both the International Society for the Study of Women's Sexual Health and the North American Menopause Society, is based upon the fact that neither term is adequately accurate or encompassing, and many people have discomfort speaking or hearing the word "vagina."

The new term, or its abbreviation GSM, is expected to be more tolerable, much as the way "erectile dysfunction" was easier for people to discuss than asking them to say "penis."

The conference concluded that GSM is more accurate, inclusive, and less embarrassing than the older terms. In addition to easing conversations, the new term will be used to develop a tool to help standardize physical examinations so that women can take advantage of treatments such as vaginal moisturizers, vaginal estrogen, and estrogen mimics.

This doesn't really change the way we think about the issue, but we do need to be prepared to recognize the new term as it starts to be more widely used. And, really, if it helps anyone open the discussion, it's a great move.

Attitude and hot flashes: an editorial

2014-06-19T10:34:00.001-06:00

May we groan with you about this article we just read? Hot Flashes? No-Sweat Attitude Spells Minimal Disruptions (free signup required).

Doesn't this sound nice and encouraging? Rah-rah? And look, not only do these people nurture their own health, but these skills can be taught.

But here's the thing about the subtext of this kind of approach. Although they're not saying it here, this implies that if women would just suck it up and not obsess about "little" things like this, their insurance companies wouldn't have to cover their hrt prescriptions. Everybody wins!

Only really not. Because in addition to furthering the old "it's all in your mind" brush-off that's so disabling for those who can't do so or who dare think that this is a problem for them, this kind of attitude really pathologizes the individual who experiences crippling disruptions. And that's more likely to be us in surgical menopause than women in natural perimenopause, for whom non-hormonal, non-insurance-reimbursible approaches can indeed also be helpful.

This is a trend in research just now, finding reasons not to treat things, and it's a trend that looks suspiciously as though it's driven by insurance companies' fiscal concerns. In recent years we've been told not to get mammograms because they're too distressing for our delicate sensibilities and my sister's husband, who narrowly survived a very early, very aggressive prostate cancer, is told he shouldn't have bothered getting tested and discovering that because most men outlive their cancers. And on and on, nearly every week I read a recommendation that testing for this or treatment of that isn't "cost effective." This is only one more study, but it's one that grates nonetheless because it undoes so much of what has been done in recent years to set surgical menopause apart as a different entity to natural menopause, permitting different treatment approaches.

Let's each of us hope that our own doctors have failed to catch this latest "news" item. And let's be gentle with each other, all of us in any kind of menopause, and remember that while attitude is very important, we're not a failure if that's not enough. We deserve wellness, each and every one of us, no matter how that wellness is obtained.

State of hrt use in menopause: what we (think we) know today

2014-06-02T14:44:00.002-06:00

There have been a lot of changes in our understanding of hrts in the past decade and a half, and it's been a tumultuous time for those in the menopausal community trying to hold onto their health as medical opinions seem to veer wildly around them. Let's take a look at a bit of history to lay the foundation for our current understanding.

How we got here

HRT use really came into vogue in the mid-twentieth century with the development and marketing of Premarin. Touted as the key to eternal youth in such popular books as Robert Wilson's 1966 Feminine Forever, Premarin was the fifth highest-selling prescription drug in the US in the final quarter of the century. It wasn't long after its introduction, however, before research began to illuminate some of the perils of unopposed estrogen, such as uterine cancer, and the long effort to reduce the risks of hrts while still enjoying their benefits really got underway.

By the 1990s, researchers were exploring the various endogenous estrogens in search of more natural-seeming and lower-risk alternatives to the mainly synthetic and mostly oral hrts then available. The thinking was that by mimicking the natural distribution of estrogens, risks could be reduced or even blocked. At the same time, Dr. John Lee was publishing his work touting progesterone in books and websites. Women were told that progesterone held the key to every hormonal complaint and it wasn't possible to take too much—in fact, the more the merrier. This even went so far as directions to apply progesterone directly to breast tissue to prevent cancer and fibrocystic breasts. Compounding pharmacists, who could blend these new, noncommercial hormones into multi-hormone blends, began selling saliva tests and advising doctors on prescribing these "bioidentical" hrts, an increasingly popular service despite the refusal of most medical insurance programs to cover them. Women were encouraged to replace all of the hormones they could test, "adrenal insufficiency" became the catchphrase of menopause, and hormone precursors were often thrown into the mix because they were "all safe, all natural."

Research, however, was gradually revealing a different picture and in 2002, everything changed. The huge US research project, the Women's Health Initiative study, was abruptly halted due to the incidence of breast cancer in one arm of the study exceeding the pre-established study limits. Overnight, popular and medical understanding of hrt went from it being a helpful menopausal strategy to it being a rapid and nearly-inevitable death sentence. Scare headlines convinced women that hrts were lethal and doctors that only liabilty lay in the path of prescribing them. Data that indicated that risks rose to an arbitrary line after five years of use were interpreted to mean that hrts that had been acceptable for five years became fatal on the following day, and women were told that there was now a firm time limit for hrt use should they be so weak and foolish as to use it in the first place. The entire message was hrt = breast cancer, and it was a powerful, terrifying message. By the end of that year, prescriptions for hrt had fallen dramatically...and so, according to several studies, had breast cancer. Much less mention was made in the medical or popular press of the widespread misery caused by sudden hrt withdrawl, but it was clear online as forums rang with tearful pleas for anything non-hormonal to stem the awful effects. While we know that breast cancer rates dropped, we don't yet have the full reckoning of the more delayed cardiovascular and metabolic price women paid for this panic.

A few voices were raised amidst the hysteria, questioning the applicability of the study results to all hrts, especially since the arm of the study involving women who had hysterectomies, and thus were taking Premarin alone instead of the PremPro used by the higher-risk participants, showed a reduction in breast and colon cancer below what would have been expected for that population. Others questioned the delivery route and age of study participants, especially with regard to the cardiovascular risks the study found.

Also a matter of concern with the study results: was this risk situation particular to Premarin, the oral delivery route, or all estrogens? While medical practice has long required that all hrts be treated as though identical in practical terms, new research was already questioning the impact delivery route was having on inflammatory factors, agents known to contribute to cardiovascular and cancer risks.

And, finally, were the study participants, mostly a decade or more post-menopause and who had not used hrt in the interim, too old to yield meaningful information about younger women using hrt from the time of menopause?

As time has passed, the study data has been re-analyzed and re-examined in the light of other current research and although this reappraisal has not engendered headlines on the scale of the study cancellation panic, the effects are in fact slowly propagating through the medical world. Where 5-8 years ago doctors advised against hrt and if used, used for only a limited time (that five years of safety/five years + 1 day = death proved remarkably sticky as a guideline), today many of the major medical groups are revising their standards back to a judicious endorsement of hrt.

The major focus of research today continues to center around risk reduction. The new understanding of route-related effects has boosted development and marketing of more transdermal, human-identical hrts, with many of the older oral and synthetic hrts fading away off the market. Greater understanding of the cancer risks associated with progestogens (progesterone and its synthetic versions) has reduced the routine inclusion of progesterone in hrt for women without a uterus and driven attempts to develop SERMS that don't stimulate uterine tissue so that women who do have a uterus aren't forced to rely upon progestogens to mitigate that risk. The question of age-related risks has focused research on the "critical timing" (also called "window of opportunity") hypothesis, supporting the notion that women best reap the health maintenance benefits of hrts when they are taken immediately upon menopause, without allowing hormone levels to drop catastrophically. And a greater appreciation of what hrt means to the quality of a woman's life and health, disastrously demonstrated by the widespread misery left in the wake of post-WHI hrt prohibition, has even led to a softening on the stance that women may take an hrt only so long.

Current understandings

Today, the standard offered by most medical groups is "the least amount of hrt for the shortest time." That's a risk-focused strategy and on its surface, sounds rather grudging. But that's not actually what its intent is and that's not how we, in surgical menopause especially, need to take it.

The "smallest dose" is only a sensible precaution that many of us have been advocating for and practicing ourselves for some time: risks accrue with lifetime estrogen exposure, so taking only as much as is required to meet our personal menopausal health goals is simply reasonable. That doesn't mean we all need the smallest retail dose, but rather, we need only as much as provides the effects we've selected as important to us. More hrt (beyond our level of needs) doesn't improve its action; it only raises its risks.

Similarly, the "shortest time" is, once again, determined by a woman's own judgement of her needs and how they're being fulfilled. We have long known that our hormone needs decline with age. In keeping with the smallest dose precaution, we should reduce our hrt dose, then, at intervals as we age. At some point, sooner in natural than surgical menopause, our declining needs curve intersects the zero dose point. And that's when we don't need to supplement any longer. That, then, defines the "shortest time," after which ongoing exposure, again, accrues risks rather than benefits.

Now, if you're reading carefully, you'll see that both parts of that standard, then, are in fact pretty subjective: it's about how our hrt meets our own goals. A doctor's role is to help us explore risks and ongoing need, but the bottom line, in guidelines document after guidelines document, is a woman's own sense of her goals and how they are being met. Everyone from the British Menopause Society, which is currently a stakeholder in the National Institute for Health and Care Excellence (NICE) developing new guidelines for menopause treatment for the NHS to help remedy some of the damages done by ten years of post-WHI hormone avoidance, to the American Association of Clinical Endocrinologists is re-evaluating the lessons of the past decade-plus and forming a more flexible and woman-centric stance on the use of hrt. And this is very good news for us.

Below, we've listed of some of the major medical groups' current menopause treatment guidelines Why? Because reading them helps us understand how our doctors are seeing the situation. And if they're not telling us things that are in accordance with these updated guidelines, we can share these with them as authoritative statements, not just the easily-dismissed "something you read on the internet."

American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause (also the designated reference for the American Academy of Family Physicians)
American College of Obstetricians and Gynecologists Practice Bulletin No. 141: Management of Menopausal Symptoms (behind paywall) summarized (free signup required)
Society of Obstetricians and Gynaecologists of Canada Managing Menopause
Updated 2016 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health (also in Spanish)
The 2020 British Menopause Society & Women’s Health Concern recommendations on hormone replacement therapy
The 2017 Hormone Therapy Position Statement of The North American Menopause Society

Why are there not more recent position statements? Because that's the last time they were updated. Which in a way is a good thing, since this means that no new and compelling evidence has been discovered that changes these positions in any material way.

Research and trends

Additionally, there are a few interesting trends that are forward-looking.

We are slowly starting to see women post-cancer-treatment electing to use hrt for quality of life, balancing this against the risks and discomforts of hormone deprivation treatment. This is typically not a measure endorsed by their oncologists, who tend to focus on preserving life at all other cost, but rather one they often work on with their general doctors. Further, the general prohibition of "you had cancer once so you can never take hrt" even when risk of recurrence is low is coming more frequently under examination as the "hrt = cancer" heritage of WHI abates.

Still, there's so much we don't yet know. The whole issue of mental function, Alzheimer's, dementia, "brain fog," loss of multi-tasking capability: this remains an area of research in which study results remain in disagreement or inconclusive. Usually in research this means that the proper situation isn't yet defined, so we can only wait while research slowly rolls on.

Exploration of the "critical timing" or "window of opportunity" issue continues, despite the problematic nature of trying to distinguish between fostering protection and preventing or treating disease. (bookmarked articles on this topic) While this is generally still referred to as a hypothesis, meaning it's not considered proven, the British Menopause Society has made the leap to "confirmed," giving it a truly arguable weight as a health strategy.

As use of progestogens comes under greater scrutiny and, in general, wanes, testosterone continues to enjoy considerable chic. Research on its risks, however, is building and the US FDA in fact turned down a testosterone hrt for women on the grounds that it was not universally effective enough to balance its risk profile. As we've discussed elsewhere in our troubleshooting libido section, testosterone seems to be helpful only in women who actually have an actual shortfall of that hormone; in other women, for whom the issues with libido are not related to testosterone levels, it's ineffective in boosting sexual desire or responsiveness and, yes, represents an unjustifiable risk burden.

Finally, SERMS (modified estrogens) continue to receive development attention as a way to capture estrogen's benefits while reducing risks. To date, these have not provided as "full featured" hormone coverage as estrogen itself, but research remains active in this potentially lucrative niche.

HRTs in practice

There are a lot of fine points to using hrts once we've got a doctor willing to prescribe them. Many of these aren't things we'll learn from research, but rather from the discussions those using them have about their hrts and how they've worked best for them. A lot of this body of knowledge is incorporated into the various articles on this site, but since we're often asked which is the "best" hrt, let's look at some of what we as the community of hrt-users have learned in the past decade and a half.

There is actually no "best" hrt. The "best" hrt is the one that works for any given individual. All hrts work for some people, but no hrt works for all people. That's why the question "what works best for you?" is so frustrating, because that's not going to answer "what will work best for me?" The process of identifying the best hrt for our own selves remains a journey of personal experimentation. Still, there are certain understandings that can help point us in useful directions.

Troubleshooting patch techniques and placement, including brand change, solves many of the problems wearers have with this hrt;
Switching from oral to transdermal solves many of the problems related to poor response to orals;
Those who do best on trickle-dosing are a distinct subset, as are those who do best on daily dosing: this seems to be an either/or situation for many;
People who have really worked the estradiol hrts without success often find that CEEs hold the key to a more comfortable fit;
CEEs and part/all-estrone hrts can help with with migraine issues where estradiol hrts have proven problematic, and vice-versa;
Gel delivery remains the most problematic, in part because we don't yet have good technique troubleshooting information (we think)(it may just be that it's a finicky delivery that we can't make better), even though some users do spectacularly well with it;
Low, slow, and estrogen-alone all seem to be the most straightforward and most comfortable ways to approach adjusting/troubleshooting hrts;
Contrary to what we thought a decade or two ago, most of us in surgical menopause do just fine without supplementing progesterone when their estrogen is well-balanced;
A well-functioning, well-delivered hrt works for most people at the usual doses, with a predictable age/dose inverse correlation (that is, younger users tend to prefer higher doses than older users do); and
The best determinant of "enough" is achievement of your own health goals.

For discussions on new research, guidelines content, or hrt troubleshooting, please join us in our discussion forums.

Tuning our hrt support as we age

2014-04-14T13:17:00.002-06:00

After all of the work we have gone through to find our best hrt and correct dose, it would be understandable if we thought our job were done. Unfortunately, that's not the case. Sooner or later, we'll need to re-evaluate where we are with our dose and whether it's still appropriate for us.

Sometimes it's a matter of our doctors freaking out and going "You've been taking hrt for HOW long? OMG you have to quit immediately!" That's not a response guided by the major specialist practice guidelines, but it is a response to popular media coverage of hrt issues, especially the cancellation of the Women's Health Initiative Study, and their sense of legal liability.

What happened was that after five years of studying several kinds of hrt use, the WHI found that in (only) one arm of the study breast cancer incidence rose a small amount that was nonetheless enough to trip the study limit guidelines and force shutdown of the program after it had gone on for five years. In the popular media, of course, the headline was "HRT kills!" And in medical literature, doctors solemnly agreed that they could prescribe hrts for five years of safe use, but one day after that five years, it was unacceptably deadly.

That's a nearly nonsensical reading of the study results. And in fact, over time and re-analysis of the results of the WHI, recommendations have come to reflect this. Most current guidelines repeat the mantra: as little as possible for as short a time as possible. Which, to phrase it more constructively, can be construed as the minimum amount that meets our needs for no longer than we require it to meet our needs.

See what they've done there? There is no calendar attached to that statement other than that provided by our own bodies and our own health goals. Aside from major and incompatible health problems, our doctors have no justification for demanding we quit and we should feel no obligation to stop using hrt at some arbitrary deadline.

Why we do need to revisit our hrt dose

Nonetheless, we do need to be sure we're paying attention to the least/shortest guideline because that does speak to our best current understanding of the risks of hrt use.

Here's the thing: as we age, our hormone needs decline. We can't freeze ourselves at one age by thinking we're supporting that by our hrt. That's an old fallacy and one with demonstrated risks. Instead, our goal is to support our needs as they are in each moment with just enough hrt to feel right.

The problem is that we tend to go along unquestioning and tiny bit by tiny bit our hrt fits us less well. We don't really notice, even, because excess tends to be a lot less dramatic than deficiency. But we may have fewer hot flashes (especially those lingering ones at 5 am) or our breasts may feel fuller or we don't seem to need our local vaginal hrt quite as frequently. It's nothing we might notice as a trend, but that's what it is.

Because of its subtlety, though, waiting until we notice it isn't the best of strategies. Instead, we will more accurately tread that important line of least risk by regularly challenging our dose. How regularly? Oh, every three to five years seems to be the sort of interval that produces useful results, although a case could be made for deliberately asking this question about a year after our surgeries as well.

So how does this work?

We're glad you asked.

When it comes time for a dose challenge, we need to look at our hrt and determine a reasonable amount to try as a decrease. For some hrts, we're limited by the doses it's sold in because we can't break the delivery form. For others, it's very easy to make a tweak.

We're looking to decrease our dose by no more than 10-15%. That amount is enough to notice but shouldn't be enough to really ignite transitional fireworks. If we have no other choice, a 25% reduction is something we might pull off without too much uproar, but beyond that it's unlikely we'll not experience some deficiency if we weren't in significant excess earlier. In other words: we're looking to eliminate that invisible creep of dose above needs, and if it were more than about 25%, we'd probably have already felt the need for change. On the other hand, if you've been taking hrt for 20 years without ever adjusting your dose, you might be there.

So we try out our new reduced dose. We can do this at any time, although it may be more successfully done in the summer (which of course means winter if you're in the southern hemisphere). That's because the withdrawal of that amount of support from our brain chemistry in particular is most smoothly adjusted to when we have other things to help out with it, things like outdoor exercise and sunshine. Women who reduce their dose in the winter (by which we mean the dark time of year), particularly when they live in higher latitudes, may find seasonal blues too overwhelming when they are decreasing their hormonal support at the same time. Remember: even when we're moving toward a better dose, we're still going to need to physically adjust to that new dose.

If we are going to be dramatically unsuccessful in our challenge, we're likely to know this within a week or two. Transitional symptoms, in which our bodies respond to any change, generally settle within three to seven days, and only after that is the adequacy of the background dose revealed. Journaling through this period, even if we haven't done it for years, can be very helpful in revealing things in retrospect that were too slight to recognize at the time.

If we are experiencing unpleasant symptoms of deficiency, then, we can determine that our dose most likely needed to be where it was. We resume our previous dose and figure okay, good for another few years.

If things seem to be going okay once the transitional symptoms taper off, however, we might as well carry on with the new dose. Which doesn't yet mean our challenge is a total success. Sometimes a dose drop can leave us with such a very tiny deficiency that it takes a long time, months even, to decide that nope, this isn't really meeting our needs the way we want. Symptoms may be very subtle with this kind of a mismatch: maybe we notice one day that we're getting creakier or we just don't feel the joy in life the way we did last year. We make these kinds of evaluations based upon what we have previously learned about how our own body demonstrates deficiency; if we develop new problems, we cannot automatically assume they're about the hrt because we are, after all, getting older.

If we experience this kind of slow deficit, the answer is still to go back up a bit in dose: there's no time limit on this. If we have the option, going up less than the full increment we decreased by would make sense; if not, we can go back to the old dose with the assurance that we're as closely tuned as that particular hrt makes possible to our present level of need.

And when our doctors ask at our annual checkup about whether we've thought about still needing hrt? Being able to say "yeah, last year I tried cutting back a bit and found that within a month I was running noticeably low and I feel a lot better now that I'm back on my current dose" is going to go a long way toward convincing them that we're using hrt responsibly in accordance with the current medical practice guidelines.

So in summary:

there is no calendar date that defines safe vs unsafe duration of hrt use;
our needs for hormone supplementation do decline slowly with age;
we should challenge our dose every 3-5 years to make sure we're using the least dose that meets our needs; and
our doctors should be impressed that we're taking care of this for ourselves.

Surgical menopause, hrts, and headaches

2014-04-14T13:07:00.004-06:00

Headaches aren't special to menopause or even the surgical variety, but for those prone to them, hrt can involve some special concerns.

Headaches due to low estrogen

This may be one of the earliest symptoms to hit us after we have a hysterectomy—once the headache from not being able to have coffee before surgery wears off! Some folks develop a lingering, grinding headache that they just can't shake until their hrt is properly adjusted to their needs. For them, headaches become a tuning symptom, something we know has a specific meaning for our own body.

If we've not immediately gone onto hrt after surgery, doctors are sometimes worried that a headache during the recovery period means we're having or are at high risk for a stroke and shouldn't have hrt. While there is validity to ruling stroke out, especially when we've just had surgery, and while there is a slightly higher risk of stroke in the first year of using an oral hrt, some women are left with their doctors' refusal to prescribe just because they are still afraid of that risk. That says something rather sad about their faith in their own diagnostic capabilities and it says something terrible about a woman being able to get the care she needs. Shopping for a new doctor can, sadly, be about the only way out of this trap.

Generally speaking, headaches due to low estrogen tend to abate pretty well once our estrogen levels are meeting our needs.

Headaches from high estrogen

Yes, this happens too.

Decreasing the dose is the right answer for risk and for this kind of headache. How can we tell which is which, high vs low? By the other symptoms that appear with the headaches, just as with any other aspect of hrt tuning.

In general, the tactic of adding a diuretic (water pill) to hrt with the goal of reducing fluid retention from excessive estrogen is not an effective strategy for dealing with this kind of headache, let alone the risks posed by excessive estrogen exposure. It's a common medical response, however, to see each new symptom of imbalance as a separate disease that requires separate medication. We need to be alert to the state of our hrt balance and, if our doctor wants to prescribe diuretics when we think we're in hormone overload, we should be prepared to advocate for our own preferences. Suggesting a trial of dose reduction before adding a new drug is not an inappropriate proposal and a doctor willing to work with us should prove amenable to this kind of trial.

If going down in dose of an hrt doesn't cover our overall hormone needs but that previous dose being the next increment up presents excess, then we can understand that to mean that this isn't the best hrt for our bodies and that we could make more progress by moving along to a new hrt. While we always advocate adjusting dose before giving up on an hrt that appears to be delivering, there's only so far we can adjust things. If we're bracketing our needs without being able to find an acceptable middle ground, we're there. Moving along is likely to be more satisfying sooner.

Headaches upon taking an HRT dose

Some of us don't consider ourselves prone to headaches but then when we begin taking hrt, BLAM. These are often those who had semi-regular headaches during their former menstrual cycle, and if so, that's a great clue we can use in tuning our hrt.

In the situation of menstrual cycle headaches or right-after-taking-hrt headaches, the culprit often seems to be the rapid rise of estrogen levels; once a woman is a few hours or days into a dose, it abates. Because every dose of hrt takes us from a lower level to a higher one, especially early in our adjustment period, we're simply recreating the hormonal setting of those earlier cyclical headaches.

For these women, the key seems to be getting onto a stable level of hormonal support and a dependable delivery, so that they're not swinging up and down with each dose. While there will always be an uptake curve at one end of an hrt dose and a wash-out curve at the other end, once we stack several days' doses on top of each other, we reach a background level of hormonal supply that keeps us supported between doses. Some women, alas, take this sort of situation to mean they need to overlap their hrt doses or take them in tiny increments under the impression that a perfectly even and continuous delivery is necessary. In fact, however, this is something our bodies can sort out for themselves if those doses are adequate to permit us that background leveling between doses. While it's still the case that some hrts will be more comfortable than others for a woman sensitive to this dynamic, there's no single answer as to which those hrts will be.

Headaches with HRT

This is a bit different from the above situation in that a person on a poorly-fitting hrt may have frequent headaches as part of a picture of poor coverage: jangly nerves, anxiety, poor sleep, mood instability, and a general sense that they're walking a knife edge of disaster, not at ease in their skin. This situation tends to persist through dose adjustments up and down and even with a change of hrts. Often, these folks come to our forums summarizing their experience as "I can't tolerate hrt."

But frequently that's not the full story. Often these users, even when they've explored dose adjustments, have pretty much stuck to the estradiol hrts. And that's understandable because most of the hrts on the market today are estradiol hrts. We tend to divide the hrt market into human-identical estradiol and Premarin, and Premarin's reputation is a difficult one for many women to embrace. Routinely, more doctors seem to be offering estradiol than Premarin (or the other conjugated estrogens), and people are choosing estradiol hrts on their own.

But estradiol is the active form of estrogen and it seems that some of us don't want that much activity dumped into our system at once. These users seem to do better whwith an hrt that is comprised of some or all estrone rather than 100% estradiol. Estrone is a much less active form of estrogen, even a storage form, and it can be much gentler in its impact.

It feels, watching what the surgical menopause community is discussing, as though this problem is showing up more today than it did, say, a decade or two ago. But that was when we more freely used progesterone to take the edge off of a poorly-fitting estrogen hrt (a practice that's waning today due to better understanding of progestogens' risks) and that was when there were more estrone hrts on the market. These have mostly disappeared, now, and we think that this has left those who prefer them more adrift in what seems to be an all-estradiol world.

If an individual has tried various routes of estradiol hrt and still doesn't feel comfortable, they may want to explore the remaining non-estradiol hrts. These include:

compounded hrts with all estrone or a blend of just a bit of estradiol with mostly estrone;
Menest, which contains mostly estrone with a bit of equilin estrone (synthetic horse estrogen, similar to some of the compounds in Premarin);
~~Enjuvia or Cenestin or a generic for them, which contain various blends of synthetic estrogenic compounds that are mostly estrone-ish in action plus a few that are estradiol-ish~~ (no longer on the market); or
Premarin, which contains a blend of synthetic estrogenic, androgenic and progestogenic compounds that are mostly estrone-ish in action.

With the exception of the compounded hrts, these are all oral deliveries, which may not be our first choice these days. Those who experience this particular problem often find, however, that they are willing to accept that profile in the interests of a better hrt fit. It really can make an astounding difference from the impact of estradiol hrts.

Migraine headaches and HRT

Migraines are a miserable affliction and for those who hoped that removal of their ovaries would put an end to a monthly brain implosion, they, disappointingly, can continue right on thanks to the efforts of our menopausal hrts.

The primary migraine triggers seem to be much like the general headache causes: hormonal fluctuations and the type of estrogen used (by which we mean, the activity of the form of estrogen the hrt contains). So when troubleshooting hrts around migraines, those are some of the considerations to work with.

Sadly, hrt alone isn't always enough to control migraines, and some women end up finding that a combination of hrt plus other drugs that are specific to migraines ends up working the best for them. Still, these hrt adjustments do give us a place to begin that can be more helpful than simply being told we can't take hrt if we get migraines.

Bioidentical HRTs

2014-04-13T14:32:00.001-06:00

There are two aspects to the confusion about "bioidentical" and what it means. Let's look at them both to try to clarify what is being talked about.

HRTs that are bioidentical

The term "bioidentical hormone" originally simply meant any hormonal agent that is identical in chemical structure to those produced by our own ovaries. That term says nothing about hormone balance or hrts; it only describes the molecular configuration.

When our body uses the hrts that contain bioidentical hormones, they are for the most part used as our own were: the metabolic processing steps are essentially the same. Why not exactly the same? Because no matter what the form of the hormone, the way in which it is delivered to the body does enter into the dynamics of the situation. When we have intact and functioning ovaries, we have only enough of our hormones in circulation at any given moment to meet our needs. This level is controlled by a number of different feedback mechanisms and in turn controls a number of other hormonal levels and other physical processes.

But when we have to obtain part of our supply from outside our bodies, we don't have any way to make that intake respond to our internal cues. Instead, the timing and form of the hrt we take builds its own dynamic, sometimes causing its own effects upon how the hormone can be used that are independent of the adequacy of the actual hormone amount averaged across, say, a 24-hour period.

One example of this would be that oral hrts, because of the intense burst of processing they need by the liver, can cause more gallstones/gallbladder attacks as well as elicit more of an inflammatory response, such that they are associated with a specific, non-hormonal set of effects. Another example would be oral progesterone use, which provides for a more neurologically active set of metabolites than when progesterone enters the body by other routes. So even though the hormone molecules themselves may be identical to our own, the route and delivery timing add their own contributions to the overall effect we see when we use them in hrts.

You'll note we don't use the term "bioidentical" on our website when we're discussing hrts. As we've noted elsewhere, we avoid using it because its original meaning has become conflated with a different meaning, pertaining to a specific marketing strategy. For clarity, then, we refer to hormones identical to our own in chemical structure as "human-identical."

Bioidentical HRTs, the business practice

The other use of "bioidentical" involves compounding pharmacies and the practice of physicians with whom they work. In carving out a new business niche for themselves in compounding hrts and advising women on them and selling test kits for hormone levels, they have chosen the term "bioidentical hormones" to describe this entire business practice. Fundamental to their marketing campaign is a philosophy expounded in the mid-90s by a few researchers at saliva testing labs, notably David Zava and Jonathan Wright, that women are best served by replacing not one form of the estrogen molecule, the active estradiol one, but a mix of the forms that mimic the blend found in a naturally menopaused woman.

This mixed-hormone concept was never really researched in a standard way other than to say look, when we test hormone levels in healthy women, this is what we find, refined by the sort of experiential "this seems to work for some women" work that we all, individually, do with hrts. There is no actual proven foundation for the premise that we best need a blend. We've written elsewhere about the three estrogens that have become the focus of this marketing approach.

What we think is most important about these three estrogens is that, speaking from the standpoint of physiology, they are not all individually necessary as original supplements. Our bodies have the innate ability to convert estrone and estradiol back and forth to meet our needs. Put in one form and, if it is human identical, it will be handled in the normal way to meet our needs, either as itself or as its other form. Estriol is a waste product, included in the belief that its limited range of effects is somehow safer in overall profile. In other words, it's filler, meant to extend the hrt effect without extending risk (although at therapeutic doses, it has been shown to not actually work out that way).

So do some people do better on this than straight-estradiol hrts? Absolutely. Some of us, for one quirk or another of individual metabolism, have trouble coping with some forms of estrogen efficiently. It may be a timing/delivery issue of plunking too much of one into our system at once; it may be an issue of not having enough of a cofactor/enzyme/whatever to carry out that much conversion at once. So yeah, there definitely is a place in the realm of hrt for blended estrogens and there are some folks who do best on them.

But do all of us need the blends? Absolutely not. Some of us don't do those conversions back as well and need a straight dose of one or another estrogen to have enough to work with. And there's no way to predict this; there's no way to test for this other than to try hrts. There's a real role for blended hrts, just as there is a real role for multiple doses and routes of all hrts, but there is no single correct answer for all of us—however much anyone's marketing would prefer to convince us otherwise.

And this is where the marketed practice of compounding pharmacists lets us down: by suggesting that there is more uniformity of hrt response than we have actually found there to be. By insisting on selling a test and then claiming to tailor an initial hrt that will correct every single level abnormality at once, this distorts the actual physiological process and doesn't take into account the way that our bodies use all of these hormones interchangeably and interactingly.

Many of the hormone level alterations we see in surgical menopause, especially when we are starting hrt in the immediate post-oophorectomy period, are responses to a sort of falling-dominos effect: one hormone loss kicks off another. So some of those levels represent a response to another imbalance, not a fundamental inability to balance that particular agent itself. In other words, if we correct one imbalance, many of the others will fall back into line of their own accord and through our own innate processing capability. By throwing a whole shopping cart of hormones at us at once, based on a test that may or may not accurately reflect either our true resources or our true needs (more on testing's limitations), practitioners of this "kitchen sink" philosophy aren't giving our bodies the chance to use our own mechanisms to sort stuff out and are throwing further sources of instability and excess into the mix. In effect, they can be artificially holding us in an imbalanced, stressed state instead of providing the resources necessary to return to an unstressed, balanced state.

An alternative approach, that espoused by the American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause (free signup required to read) takes a much more physiologically-justified direction in suggesting that we should deal with one hormone at a time in a descending order of priority. By alleviating, first, the priority estrogen need, we allow other hormones to ease back to their own innate levels, thus revealing whether or not we actually do have abnormalities in our ability to provide for them, as distinguished from abnormalities of supply due to borrowing from them to meet higher but unmet priority needs.

Compounding pharmacists make more money the more hormones we buy from them and the more times they have to test and readjust those hrt blends. It's a business model, not a primary health care delivery mode. And it's one that has been helped along by marketing in the publishing business, where celebrities further confuse this issue with their own books that promise all sorts of sexy wonders if we'll only buy into this or that program that they themselves are marketing.

Please don't get us wrong—there are many excellent and knowledgeable pharmacists, but diagnosis and treatment are not part of their professional preparation and certification. There are many good things that compounded hrts can do for us, like provide more flexible dosing or blends that may suit our own bodies needs better than retail options, but the industry of "bioidentical hrts" as it has come, in the marketing sense, to mean this test-and-kitchen-sink program, is not necessary for most people in menopause from a health/wellness standpoint.

And so our biggest concern is that as a result of the conflation of these two concepts, the pure biochemical definition of bioidentical and the marketing concept, hrt customers are in a sense deprived of an opportunity to fully understand their choices. There are many retail human-identical hrts, and yet current marketing (as well as the anti-hrt crusaders') efforts have made it seem as though the compounded combo hrts have as their only alternative Premarin. All prescription retail hrt is not Premarin, and yet that is the implication that many many of us have been brought to believe. This is a deception and misconception that distresses us on behalf of all of those who won't find their best choices because they don't know that more exists or they feel they cannot afford to use something "bioidentical" because the package the pharmacist is offering them is too expensive.

There is a place in the market for each and every hrt that exists today, as well as many that do not and that we can only dream about. There are those for whom the "kitchen sink" works the best; there are others for whom nothing but Premarin works. What we would prefer is that each one of us be given a chance to find where on that continuum of choices we fall, not to feel that we have to choose between one end of it and the other because the rest is invisible thanks to marketing by pharmacies, drug reps, doctors, publishers, anti-hrt crusaders, insurance companies, and all of the others who seek to profit from our confusion and discomfort.

My hrt stopped working!

2014-04-13T13:12:00.001-06:00

There are two different situations in which women might feel as though they are getting along fine on an estrogen HRT and dose and then things go...askew. It's an obvious thing to do to assume that the HRT has "stopped working," but in fact that's generally not actually the case. Let's look now at these situations in a bit more detail.

When we start a new HRT

In this first case, we may experience this effect when we start a new HRT: we feel improved estrogen uptake for a few days, and then our improvement seems to evaporate.

What's most likely going on is that the situation of poor coverage before beginning the new HRT/adjustment had our system stressed. This means that we were borrowing from other systems to prop up our estrogen levels, the usual technique for meeting high priority needs using lower-priority resources. When we then add more estrogen into the situation, we feel that boost initially. But pretty soon word gets out and all those other systems that were being shorted start taking that loaned-out support back. So what was a comfortable supply suddenly is less so.

That doesn't mean we're worse off: we're actually in better shape than we were because we're operating under less stress. But it does mean that we'll probably need another upward dose tweak once we've given things some weeks to settle in.

Weeks!? Yes, because this take-back process isn't a single one: it happens over 6-8 weeks in a series of small iterations. This is one of the arguments for the "take it slow" aspect of gentle-on-the-body HRT tuning. There's no sense to tweaking (by which we mean fine-tuning; obviously if something's terribly off, we need to intervene before that) before we're settled in and all of these readjustment processes have played out. Why not? Because that just involves a long chase and a real risk of dosing ourselves up into excess. It's clearer to wait until we can see the target before we try to reach it.

Months or years along in hrt use

The other situation in which we suddenly feel as though we're not getting what we used to out of our hrt happens months or years along in HRT use. We felt mostly fine, but now we're clearly not. Did our HRT "stop working" in this instance? Nope.

In fact, in this kind of situation the element that is most likely to have changed is us, not our HRT. There are lots of things that might produce this effect. Maybe

we moved to a new location with new exposure to environmental estrogens
we changed our diet (becoming vegetarian or vice versa can have a big impact)
we changed jobs such that we're eating lunch in a different part of town/different restaurants
we changed supermarkets
our supermarket changed distributors
some sort of unreported toxic spill happened
our stress level changed significantly
we started or stopped drinking or smoking
we lost or gained a substantial amount of weight
we took up or quit an exercise program
we changed our brand of sunscreen
our pharmacist or insurance company changed us to a new generic or a different HRT altogether
climate change brought warmer weather that may be affecting shipping or wearing our HRT

All of these things and more are possible disruptors of longstanding hormone balance but because we don't think of them as hormonal factors, the changes they represent are essentially invisible in terms of how we think about our HRTs. But none of them represent HRT failure: they just mean that we need to tweak our dose a bit to account for present circumstances. And that's an important distinction to keep in mind.

Troubleshooting gel HRTs

2014-04-06T16:17:00.003-06:00

The latest HRT delivery on the market is the gel, and because it's still being heavily promoted by the drug reps, it's the current chic in HRT. Lots of new customers are being given gels as their first HRT. Lots of users are being given gels when they've had difficulties with other HRTs. But this HRT isn't entirely straightforward to use and our experiences with other HRT forms may not prepare us for using this one properly.

We're certainly seeing more people coming to the forums lately complaining of problems with gels, but it's hard to tell from the numbers who are online talking about problems just how widespread a problem is: those without problems aren't talking about it and are invisible to us. Still, it feels as though a disproportional number of new questions about poor HRT fit are coming from those who are trying to get comfortable on gels. In part, that may just be that we don't yet know how to use them most effectively because we don't know all of the little tweaks that, say, make patches work considerably better. We're going to take a look here at what we do know and see what guidance we can develop.

Fair warning: the material in this article is long and a bit denser than usual. We think it's important stuff, but if you really just want to skip over the background and get to the "to do" list, skip ahead down to the final summary.

How gels deliver

A gel HRT is different to a cream in that while a cream is absorbed through the skin and into the tissues below it, where fat forms a buffer to pace its onward delivery, a gel dries on the skin so that the drying and the skin itself form the only buffer. This means that the gel sits either in the top layer of the skin or is in circulation; there is no other location where it pauses in between.

There is some discrepancy, though, as to exactly the extent to which what is on the skin remains part of our reservoir of hormones. On the one hand, in Pharmacology of Estrogens and Progestogens:

The application of a hydro-alcoholic gel containing estradiol results in a rapid penetration of the estrogens into the stratum corneum; this stops after drying of the gel on the skin. As the absorption is proportional to the surface of application, deviations from the instructions may cause variations in the estrogen level and clinical efficacy. About 10% of the dose is absorbed by the skin during the 2 min until drying. The estradiol is stored in the stratum corneum and permeates through the epidermis into the dermal capillaries according to the concentration gradient between the stratum corneum and blood. This diffusion lasts for 2-14 h. The two available gel preparations differ in their concentration and mode of application.

On the other hand, in the Divigel package info, we have:

Washing the application site with soap and water 1 hour after application removed all detectable amounts of estradiol from the surface of the skin, and resulted in a 30 to 38 percent decrease in the mean total 24-hour exposure to estradiol.

Looking more closely at the skin, it's made up of a number of layers:

We can see that the stratum corneum is the top layer, just under the collection of dead cells and rubbish that make up the actual surface that we can touch. During the drying time, the dose we'll actually have available to us migrates into the stratum corneum. This creates the dose reservoir, from which the estradiol is then diffused into our systems over the next 2-14 hours, safe from mechanical removal. But, and this is a critical "but," it seems it's not safe from external influence entirely.

On the one hand, once the gel has dried, a process our first source says takes 2 minutes, we're to believe we've got a done deal, so to speak, and the working portion of the applied dose is ours to use.

But we know from the second source that washing even an hour later removes the remaining unused and unabsorbed-into-stratum-corneum portion of the dose and although we'd expect any effect of that to be insignificant based upon the first reference, we see in the second that it's not as protected as we would infer; washing within an hour is said to reduce the dose delivered by 30-38%.

So that portion of dried gel that rests atop the skin, above the stratum corneum, is in some way still an active component of the daily hormone dose. And this means that we do in effect have a dual reservoir here:

The amount of hormone that penetrated to the stratum corneum, which, if the amount on the skin is undisturbed, provides for the full daily dose release and uptake by circulation over 2-14 hours, and
The dried amount of hormone perched on the outermost layer of skin, the premature removal of which will reduce ultimate delivered systemic dose by 30-38%.

Why are we going into this in such detail? In part, successful use of this HRT and the precautions we must practice with it depend upon our understanding of its vulnerability to outside influence and losses. In effect, this HRT is like a patch without the backing, and it's not going to perform well for us unless we undertake its protection properly.

Before we leave the delivery issue, we do want to say a couple things about how this particular form of delivery fits in the overall spectrum of different effects upon our bodies. This is a transdermal delivery form, so it will work best for those who have skin permeable to estradiol. All four gels currently on the market deliver human-identical estradiol, so comfort with all-estradiol HRT defines another subgroup for whom this HRT will work better (or worse, in the opposite case) than some others.

But because of its unique on/in skin reservoir, the uptake from a gel could be somewhat faster than with creams, such that it's probably more easily considered a somewhat slower version of a transbuccal dose, with more of it entering the body initially but, with gels, a small amount still migrating through as the day goes on. We should therefore think of a gel as a daily-dosed delivery, not a trickle-dosed delivery like a patch, even though the end time for the gel delivery is sort of open-ended. And like all daily-dosed HRT, we should take this one in the morning, in a single dose, if we want it to best fit with our systemic circadian rhythms.

Why this delivery can be problematic for us

One of the most important aspects to understand about gels is that they have a huge amount of wastage built into them. We'll look at the dose numbers in a bit; right now, we want to focus on the mechanics.

First, let's take a look at the use instructions for the four major gels, two from the US and two from the UK. US brands are required to label with some information that is not on the European labels, and yet this can be helpful in understanding how to use gels consistently. All of this information is direct quotes from the product sheets unless it is (in parentheses like this), in which case it is our comment.

Sandrena Gel:

The Sandrena dose is applied once daily on the skin of the lower trunk of the right or left thigh, on alternate days. The application surface should be 1-2 times the size of a hand. Application of Sandrena on area of 200-400 cm2 (size of one to two hands) does not affect the amount of estradiol absorbed. However, if Sandrena is applied to larger area absorption decreases significantly. To some extent, however, the estradiol is stored in the subcutaneous tissue from where it is released gradually into circulation. (Directions note not to wash for one hour after application, but no quantified details on loss are provided.) Do not store above 25 °C.

Oestrogel:

The correct dose of gel should be dispensed and applied to clean, dry, intact areas of skin e.g. on the arms and shoulders, or inner thighs. The area of application should be at least 750 cm2. One measure from the dispenser, or half the prescribed dose, should be applied to each arm/shoulder (or thigh). (Directions note not to wash for one hour after application, but no quantified details on loss are provided.) Do not store above 25°C.

EstroGel:

The gel is applied over a large area (750 cm2) of the skin in a thin layer. The recommended area of application is the arm, from wrist to shoulder. Site washing 1 hour after the application resulted in a 22% mean decrease in average 24-hour serum concentrations of estradiol. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

And from the patient instructions: "To get the best effect, wait at least 2 hours before showering/swimming to allow the drug to be absorbed through the skin."

Divigel:

The application surface area should be about 5 by 7 inches (approximately the size of two palm prints). Washing the application site with soap and water 1 hour after application resulted in a 30 to 38 percent decrease in the mean total 24-hour exposure to estradiol. Store Divigel packets at 20 to 25°C (68 to 77°F). Excursions permitted to 15 to 30°C (59 to 86°F).

The washing exclusion is pretty important because that tells us how the reservoir can be reduced by not taking the correct care of the application site. In terms of the application, the Euro labels just give the hour-without-washing caution without quantifying the problem. In the US data, we see how much difference it can make: loss of a quarter to a third of our intended delivered dose. And we should be clear that this isn't just about deliberate showering: going out into heavy rain, swimming, getting heavily splashed while washing the dog, or even just sweating heavily all can carry the same risk of removing our dried gel reservoir prematurely.

Further, some users have reported that washing even 5-6 hours after application has resulted in hormonal symptoms that seem to indicate dose delivery alteration. This doesn't really surprise us: the subject pools for drug license applications are very small and the results very tightly groomed to present a cohesive picture of product efficacy. We in surgical menopause are a small portion of the product market and not always a typical one, and this could be one place where our more complete reliance upon our HRTs is going to show up.

So while that first hour seems to be the major uptake time, there is still the "long tail" of uptake from the skin that seemingly can be altered by losses later in the day. Or, now that we think about it, simply re-wetting that pool of estrogen sitting on the skin, perhaps allowing more of it rather than less to be absorbed. We're not sure, as well, about the dried gel's solubility in sweat as opposed to alcohol (which is the major vehicle in the gel), but we know that sweating opens pores and allows enhanced uptake of a lot of things applied to the skin, so we think we'd be safer to assume that at least some amount of uptake is changed by sweating.

The other area where the US labels hold more information is in the storage criteria. They all recommend the same "room temperature" holding, but that maximum may well be exceeded in an un-airconditioned home in the summer. The additional information of "excursions," which simply means the extremes to which storage can go before the substance is definitely affected, is especially useful. If damage to the HRT begins to occur at temperatures in excess of 86F/30C, then leaving them sitting in our car on the way home from the pharmacy while we shop or storing them in an un-airconditioned home during the summer could in fact exceed these limits. We should probably also question temperature effects when HRTs are delivered by mail to a home postal box, carried around by a postal courier and then sitting in a hot box on the side of a house or out on the street. For those users who do fine with a gel all winter only to find that in the summer it suddenly "stops working" for them, this is a possible explanation of why that might happen and offers a focus for troubleshooting efforts.

Now, it's important to keep in mind that the dose application directions vary according to the strength of the gel, so they are not interchangeable (although the fact that one goes on the arms and one the legs is not an absolute for each brand). In fact, there are two strengths/methods of dispensing of gels, one of each available in each country. There's more on the whole dose strength issue below, but what is critical about this, before we leave this section, is that the delivered dose of the hormone is only 13-20% of the amount applied. So there's a very large element of wastage built into the dose already. If we have thermal degradation of the product or excessive losses due to sweating, then, we'll be making a relatively notable incremental change in our delivered dose.

This whole issue of losses is probably a significant factor, then, in the uneven and seemingly random results some women are having with this hrt. Even the patch is pretty binary: stuck down or not. But other HRTs and products haven't prepared us for this more vulnerable delivery, and so it may not occur to users (and even if they read the instructions it may not be clear) that it's not enough just to apply a gel; we also have to treat it carefully in transporting and storing it as well as once it's on our bodies. And that is fairly different to our experience with other HRTs.

Why this delivery is problematic for others

So far we've been focused on the people actually using the gels. But if gels are as easy to lose from our skin as they seem, that also raises the specter of transferring them to others around us: family, pets, and even strangers. That's not an idle fear. Let's see what the product information says about this:

Sandrena: nothing

Oestrogel:

The gel should be applied by the patient herself, not by anyone else, and skin contact, particularly with a male partner, should be avoided for one hour after application."

EstroGel:

The effect of estradiol transfer was evaluated in 24 healthy postmenopausal women who topically applied 1.25 g of EstroGel once daily on the posterior surface of 1 arm from wrist to shoulder for a period of 14 consecutive days. On each day, 1 hour after gel application, a cohort of 24 non-dosed healthy postmenopausal females directly contacted the dosed cohort at the site of gel application for 15 minutes. No change in endogenous mean serum concentrations of estradiol was observed in the non-dosed cohort after direct skin-to-skin contact with subjects administered EstroGel.

That above is in the clinical pharmacology section of product sheet; the patient instructions say just

Cover the application site with clothing (such as a long-sleeve shirt) to prevent others from touching the application area and being exposed to the drug. Wait at least 1 to 2 hours (depending on your brand) before allowing others to touch the skin where the medication was applied. If someone accidentally touches the gel (or the application area within 1 to 2 hours), have them wash the area of contact on their body with soap and water as soon as possible.

Divigel:

"As with most topical products, there is a potential for estradiol transfer following physical contact with Divigel® application sites. The effect of estradiol transfer was evaluated in healthy postmenopausal women who topically applied 1.0 g of Divigel® (single dose) on one thigh. One and 8 hours after gel application, they engaged in direct thigh- to- arm contact with a partner for 15 minutes. While some elevation of estradiol levels over baseline was seen in the male subjects, the degree of transferability in this study was inconclusive." and "The application site should not be washed within 1 hour after applying Divigel®.

This sounds to us as though there's a transfer risk that lasts at least as long as the time before we can wash the area, and that washing the area and covering it with clothing are the only remedies offered by the manufacturers. But we know from the information we looked at near the top of this discussion that washing also reduces the estrogen delivered. So we have to give up a portion of our dose, then, to protect our pets and families. That doesn't mean it's impossible to reconcile the two needs, but it does contribute to making use of this HRT less intuitive.

But in fact we're not sure that it's even this simple. What happens to the estrogen that gets on that long sleeve and then goes into the laundry? Does it get redistributed through our family's clothing? How about the towels we used when we washed? The notion that having a sleeve over it keeps the estrogen from passing along seems overly simplistic, and that really we can consider this a temporary buffer but not a definitive capture and disposal. Besides which, wearing a sleeve over it in the summer or when our job attire calls for something different seems like more of a limitation than other HRTs require, not to mention the whole issue of what one does if, say, they work out daily by swimming laps in a public pool.

Beyond that, even, we have a broader environmental and social concern. If we're going to be washing this not insignificant portion of our dose down the drain every day, that dose is going into municipal wastewater treatment facilities or into the ground, from both of which locations it will migrate into water supplies. Neither wastewater nor drinking water treatments require removal of estrogens (along with lots of other drugs that are flushed for disposal or peed out every day). So this puts those estrogens into the water used by animals and other people, exactly what we find when we examine the environment for xenoestrogens that have been linked to higher rates of hormone-exposure disorders and earlier sexual maturing. We're not going to take a stand here about the ethics of this because that's not the focus of this site. We do, however, feel that it's only responsible that we point this out to the menopausal community and ask each of them to make up their own minds on this issue.

Calculating gel doses when the math makes no sense

Doses of gels, because they are meant to experience such losses, can be really confusing. Manufacturers structure the stock dose iterations they market to take the losses into account and provide a specific delivered dose, so that makes the total provided dose look wildly higher than other HRT forms when they really aren't.

Beyond that, however, is the fact that because of this provided/delivered discrepancy, we can't just multiply the stock doses and have the delivered amount multiply accordingly. There's a dilution effect from multiplying the gel vehicle and a further effect upon drying/uptake time. This makes for some very counterintuitive math, but if, for example, you have the 0.5 mg dose packaging of some gels and take two of that dose, you can actually get a lower total quantity of delivered estrogen than if you took the same brand of gel in the 1.0 mg packaging.

Yeah, this kinda makes our brains hurt too. One of our members has compiled a wonderful spreadsheet of all of the transdermal estrogens and what the various stock doses contain compared to what they actually claim to deliver. That should help make things clearer when trying to compare a gel to other HRTs in general coverage or when switching to or from a gel HRT. And yes, we'd normally expect our doctors to take this into account when writing our prescriptions. But in fact we've seen some notably uncomfortable miscalculations on the part of doctors as well as users, so it seems best that we should be able to double-check things for ourselves.

How to apply the gel

Since the gel dose delivery is based upon things like area covered and drying time, we need to be quite careful indeed to follow the instructions that came in the product information with our prescription. Further, because each of the gels in a given country are different, if we change brands for any reason, we need to adjust our technique to the correct one for the new brand.

Dose customization is possible but not facilitated by the way the gels are packaged and dispensed. Pump dispensers are reportedly not entirely accurate in amount dispensed already, so the idea of trying to measure out a partial pump strikes us as particularly prone to unreliability and inconsistency. Gel packets are also a problem to partition without measurement. While the tactic of transferring gels from either style of packaging into a syringe is always possible and would result in more accurate measurement, it's also a fiddly task that can result in wastage. Re-use of the remaining portion of a dose from even a capped syringe is also questionable, given how evaporation of the alcohol vehicle would affect the spread and drying of any held-over portion.

Can we adjust our dose by manipulating our application technique? This seems likely, although difficult to calculate with any assurance. The smaller the area the gel is spread upon, the more slowly it will penetrate into the stratum corneum because this isn't an instantaneous process. The smaller the area, the longer the waiting line to get in between each cell, if you will. In contrast, the wider the area of application, the thinner the layer so the shorter each "waiting line" is and the faster the overall dose uptake.

However, we also have a drying time variable involved here, and that will to some degree offset this. For the smaller area, the gel will be deeper and hence take longer to dry; for the larger area, drying will be faster, thus providing a more limited time for the hormone to migrate into the skin. There will obviously be a small environmental component here as well, to do with humidity both in the air and in the skin.

In trying to use this form of dose tweaking, then, it makes sense to apply the dose as directed in the initial use of the particular HRT, starting with measuring out the intended application area. This gives us a baseline at which we can hope we're getting the dose and dose dynamics indicated in the product literature. We should, as with all transdermals, try hard for application consistency as it is tied so closely to dose quantity. And then, once we've got 2-8 weeks of consistent dosing, we should be able to use what we know about changes in application to fine tune our dose if that is needed.

Beyond that, how can we maximize the accuracy of our application? A number of the usual transdermal precautions apply. It should go on clean skin that has no other skin care products applied to it. The application area should not, however, be freshly shaved or scrubbed or overly warm (exercise, sauna, hot tub) because the open pores and enhanced surface circulation that heating causes will affect uptake time (in the direction of excess rapidity that might be uncomfortable) and perhaps quantity, since skin permeability will be affected. It might well also sting, since alcohol tends to do so under those conditions.

We've talked about not washing or wetting the area too soon and the need to wear clothing over the application area to protect others from accidental contact. But because of where the reservoir for this HRT lies, both on and in the skin, we also need to be very aware of other substances that can alter the uptake of the estrogen. This includes both things that are already on the skin when we apply the gel, which may either create a barrier to or foster enhanced uptake of the gel contents, and things that are applied after use, which may carry more of the hormone into our bodies than intended or block use of that dried reservoir atop our skin.

The patient information leaflet for Ostrogel cautions about interference of all of these products with gel use:

Skin cleaners and detergents e.g. products containing benzalkonium chloride or sodium lauryl sulphate, other skin products containing alcohol e.g astringents or sunscreens, products to treat skin and scalp disorders e.g. products to cure warts, acne or dandruff, other skin medication which change how skin is made, e.g. anti-cancer products

Now, sodium lauryl suphate is a surfactant used in many shampoos and body care products as well as most laundry products. But we have no way to know how much exposure to this is problematic: used to wash the area of application or generally used to wash one's body or transferable from our laundry? We just don't know, there's not data out there from the manufacturers, and we can't even find any useful published research.

Some of the skin care products the manufacturers seem most concerned about are sunscreen and moisturizers. This is a tricky class of products, in that there are many categories of formulations and it's not clear in which ingredients the problems actually lie. But the EstroGel product literature tells us this (emphasis added):

The effect of sunscreen and moisturizer lotion on estradiol absorption from 0.06% estradiol topical gel was evaluated in a randomized, open-label, three-period crossover study in 42 healthy postmenopausal women. The study results showed that repeated daily application of sunscreen for 7 days at 1 hour after the administration of 0.06% estradiol topical gel decreased the mean AUC0-24h (amount taken up in 24 hours) and Cmax (peak concentration of dose) of estradiol by 16%. Repeated daily application of moisturizer lotion for 7 days at 1 hour after the administration of 0.06% estradiol topical gel increased the mean AUC0-24h and Cmax of estradiol by 38% and 73%, respectively.

The effect of daily application of sunscreen/moisturizer lotion on estradiol absorption, when sunscreen/moisturizer lotion is applied before administration of 0.06% estradiol topical gel, was not studied.

And that's backed up by data on Elestrin, one of the other gels, where they found that a week of sunscreen use, regardless of whether it was applied before or after the HRT, effectively doubled the delivered dose. Their answer for this, by the way, is that we shouldn't wear sunscreen for seven consecutive days; no mention is made of what happens after six and a half days of sunscreen use or whether we're reset to zero effect after taking a day off. Head spinning? Yeah, we simply don't know enough about this dynamic.

What's interesting beyond just the application precautions in this is that we know from other research that sunscreen itself can contain estrogenic agents. Is that a factor here? We're not likely to know, since aspects of hrt efficacy are generally not tested to that degree. The only possible take-away from this all is to know that sunscreen can be problematic with any HRT, is especially problematic with transdermals, and definitely a problem for gel use. If a woman needs to wear sunscreen regularly, this may not be the HRT for her. On the other hand, for limited sun exposure, the fact that the gel application site already needs to be covered with clothing may be all that is needed to protect it and sunscreen use can be limited to only those portions of the body that are bared to the sun.

As for the rest of it, moisturizers and washing products, we just don't know how to advise you. The bottom line is most likely that trying it out with your own personal lifestyle is the only way to tell.

Don't expect your doctor to necessarily understand if you have problems with it, however, because they're not being given this kind of in-depth information in their training and will only come across it if they happen to read the product data sheets very carefully. For example, in the continuing education section of the website for the American Society for Reproductive Medicine, in a 2017 entry titled "HRT: Translating New Methods and Formulations into Patient Satisfaction" that is from a drug-company-sponsored symposium, it is explicitly stated that "Once absorbed, the gel is unaffected by the application of moisturizers or sunscreen." The symposium information also fosters the implication that any problems women have with this product are their fault, in that "some problems with adherence" is pretty much the only problem other than skin irritation noted in the use of gel HRT.

Final summary

Okay, for those who don't want the full background, here's the bottom line:

We need to follow the application directions in the package insert for our own brand of gel scrupulously;
we should avoid anything that will wash the gel off within the first few hours after application;
we may need to be consistent about things that will heavily wet or wash the gel away as much as six hours later;
gels may not be suitable for very hot climates/heat exposure;
gels and sunscreen or skin moisturizers don't mix;
we need to read the instructions for and take precautions to avoid transferring the hormones in our gels to family members and pets;
we need to think about the implications of washing off so much estrogen into the environment; and
our doctors may not have nearly this detailed a background into the complexities of using this kind of HRT.

Primary Prevention of Cardiovascular Disease With HRT

2012-01-05T12:43:00.001-07:00

We've just bookmarked an important new article that we think really brings home the post-Women's Heath Initiative Study (WHI) thinking on the flaws of that study and what we really need to know about the cardiovascular risks of hrt. Why should we care when cancer terrifies us? More of us will die from cardiovascular disease than breast cancer. It lacks the drama and publicity, but that doesn't mean we shouldn't pay very serious attention indeed to this aspect of our health.

Primary Prevention of Cardiovascular Disease With HRT (free signup required to read)
Kate Maclaran; John C Stevenson
01/03/2012; Women's Health. 2012;8(1):63-74

Abstract

Prevention of cardiovascular disease has increasingly important health implications as our population ages. Menopause is associated with the development of cardiovascular risk factors and there are many plausible biological mechanisms through which estrogen may confer cardiovascular protection. Despite a wealth of observational data to support the use of estrogen, large randomized controlled trials failed to demonstrate a benefit. It is now becoming clearer that the beneficial cardiovascular effects of estrogen are greatest in younger women and those closest to menopause. This has led to the development of the timing hypothesis. Use of age-appropriate estrogen doses is crucial to maximize cardiovascular benefits while minimizing risk of adverse effects such as venous thromboembolism and stroke.

Article summary

The article gives an excellent overview of the current thinking on how hrt use relates to cardiovascular disease, taking into account WHI data, the "critical timing" hypothesis, as well as the combination and route of hrts, both conventional hormones and those that have been modified (SERMs).

It starts out by spending some time going through the various cardioprotective mechanisms of estrogen, including metabolic ones related to lipid levels and fat distribution, insulin resistance, and actions on blood vessels themselves. It then introduces a review of the data from the disastrous Women's Health Initiative Study and looks closely at why this was in such contradiction to a substantial body of sound other evidence.

Crucial differences in the study populations are likely to help explain many of the discordant findings. The observational studies generally involved women who started HRT around the time of the menopause for symptomatic relief. Subjects tended to continue treatment consistently and were followed-up for a long duration, often 10–15 years. By contrast, women in the WHI studies were started on HRT at an advanced age (average 63 years), often with a significant delay following menopause. Furthermore, subjects had elevated BMI, were not using HRT for symptom relief (only 12–17% had moderate-to-severe vasomotor symptoms) and generally had much shorter duration of treatment and follow-up

While research studies cannot assume any reason for observations, the article notes that

The presence or absence of vasomotor symptoms in study populations is important as hot flushes are increasingly being recognized as a determinant of vascular health.

That means, in research terms, that they must now state that hot flashes cause cardiovascular disease. But because we're not researchers, we can read into that the premise that this more likely reflects an underlying commonality, and quite likely demonstrates the difference between women who are not meeting their hormone needs or are fluctuating a lot, vs those who are hormonally adequate and stable. For now, though, this implied causality results in the conclusion that

further evidence is needed to help fully understand the mechanisms by which vasomotor symptoms may influence cardiovascular risk.

One of the important aspects of hrt use and cardiovascular disease is that the payout time is quite long.

This theory is supported by further analysis of the WHI estrogen-only arm, which demonstrated that lower cardiovascular event rates in women receiving estrogen compared with placebo only appeared to emerge from 7 years onwards...Similarly, data from the WHI estrogen plus progestogen arm showed that CVD benefit only appears in younger women after at least 6 years

Why is this important for us? Too many women are given hrt briefly after surgery and told they will be discontinuing it in a few months when their menopause "goes away."

Other women run up against the pretty generally accepted current guidelines that state that

HRT should be used for the shortest possible duration, often interpreted as less than 5 years.

That magical 5-year figure actually is another bit of fallout from WHI, in that it was after five years of study progression that the cancer figures for the combined hrt arm (not for the estrogen-alone arm—and this is a critical difference often missed in the panic) crossed the arbitrary threshold for study cancellation. So, nothing about cardiovascular disease is in that limit, even though it's cardiovascular disease that kills more women than breast cancer.

The article goes on to note that these kinds of time limitations may need to be re-evaluated in the light of the long pay-out on hrt when measured against cardiovascular disease, and this is likely an important and valid issue for all of us in surgical meno.

Next up: the "timing hypothesis." Succinctly stated, this holds that

there is a window of opportunity where HRT may be beneficial for prevention of CVD in younger women, but that in older women, it does not appear to have the same benefits.

But what about the bad cardiovascular outcomes in WHI? The article reviews the potential negative effects of estrogen, but then brings things into a context that is rarely seen in these discussions: need and dose and combination of hormones.

Although these potentially adverse effects of estrogen have been identified, it has been suggested they are not harmful except when inappropriately high doses of estrogen are used, or in the presence of certain progestogens, particularly MPA, which acts to negate the beneficial effects of estrogen and may cause vasospasm.

Ah, here we have the "new" thinking on hrts and this brings things much much closer to what we as women using hrt have found: dose, combination, and route all make a difference; hrts are not a single monolithic entity in which giving any random one stands for the effects of all. Seriously—please consider standing up and cheering at this point: it's that radical a departure from traditional thinking on hrts.

Is there firm data that these things really make a difference? No, the article notes that this is the direction thinking is going and that studies being conducted now should be clarifying this relationship as they are completed.

The article then looks at specific forms of cardiovascular disease that are worrisome based upon WHI results. In terms of stroke, which is what caused the ending of the estrogen-alone arm with a 32% increased risk, the authors provide supporting data from more recent studies that find that route and dose are critical to these outcomes and, not surprisingly, lower doses and non-oral hrts reduce this rate to "extremely low."

Similar insight is found into the issue of venous thromboembolism (blood clots): route and dose and specific hormones make a big difference.

oral, but not transdermal, therapy was associated with increased risk of VTE and also that the thrombotic risk differed depending on the progestogen used. There was no increased risk with micronized progesterone, pregnane or nortestosterone derivatives, but significantly increased risk with norpregnane derivatives.

Overall, there is still not a good solid body of research evidence that pits one hrt against another for route and dose. It's well enough demonstrated that different hrt types and routes have different specific effects, and it's worthwhile, as we make our own hrt selections, to review these—the article does a decent job of listing them and providing citations for the actual research. At the moment, based upon their overview, their conclusion is that

the dose of estrogen is probably more important than the route of administration on the risk of CHD, whereas both route and estrogen dose can influence stroke and VTE risk.

Estrogen, we've long emphasized here, does not act in a vacuum. While the use of progestogens (progesterone-like hormonal agents) in surgical menopause is probably declining, it remains a critical element for the prevention of endometrial cancer and endometriosis growth and continues to be popularly pitched to women by hormone marketing, especially in the compounding realm. The article takes a look at the existing data on different protestogens, noting that it's "the androgenicity of progestogens [that] influences their metabolic effects." Any woman who requires a progestogen as part of her hrt should read this section as she considers the overall effects she both wants and must avoid.

Tibolone and the selective estrogen receptor modulators (SERMs) are often offered to women as being "safer" than actual hormones while still holding benefits of other types. There's not a lot of data on cardiovascular disease aspects of their use, but this section of the article does summarize what exists. For women without specific risk factors that require these treatments, the lack of good data on their risks should certainly raise a flag that they cannot be taken as completely benign and that simply choosing them in fear of one thing, usually cancer, may raise other risks. As ever, it's all about balancing risks and to do this effectively, we need to set aside our fears of one specific boogeyman and look very specifically about our own personal risk factors in a number of areas. This section begins to lay the groundwork on this category of hrts.

Finally, in conclusion they sum up the situation:

CHD forms a significantly greater burden of disease than breast cancer or stroke, and the menopause is a pivotal time for reducing future cardiovascular risk.

They note the importance of lifestyle and diet in overall risk management, something that we would like emphasize here as well. They go on to note that

Cardiovascular risk is determined by a combination of genetic, lifestyle and environmental factors, but sex steroids can play an important role in modulating risk.

And then for the payoff:

Current evidence points to a window of opportunity, where greatest benefit in preventing atheroma progression is seen when HRT is initiated early after menopause. HRT may cause adverse cardiovascular effects through coagulation activation and abnormal vascular remodeling, although the use of age-appropriate doses and transdermal routes can help minimize these risks.

And that, right there, is where WHI was trying to go but, due to flaws in the study design, went dangerously and disastrously astray.

Important points to take away from this article

First of all, it is a good overview of the whole topic, appropriate for us to read and share with other women but also appropriate to share with our doctors should they still be stuck in the post-WHI "OMG HRT kills!" mentality.

While there is much mention made these days of a woman's "individual choice" there are still many, many women, even in surgical meno, who feel pressured to "do it the natural way" as though there are some merit points to be won in withstanding misery and poor health. We think articles like this are things all women at perimenopause or surgical menopause should read, so that they better understand that against the "all natural" glamor can be stacked the true risks of the situation. This article is good on true risks.

Hot flashes cause cardiovascular disease. As noted above, it's likely that over time and with more research, this will be seen as a profound oversimplification, in which we have a correlation rather than a causation. Never mind; for the moment we can use this to our advantage if we are being denied hrt and feel that we must campaign for its prescription.

Cardiovascular disease prevention is not a case for treating hrts like drugs: this is the antithesis of a quick, dose-related response. Instead, we need to take a longer view of hrt use when we're talking cardiovascular disease, and so while the "least dose required to meet needs" premise of risk management is not at all contradicted here, the arbitrary discontinuation of hrt at some set age or interval is strongly called into question. This is important for us to understand and very important to convey to our doctors if they are not conversant with current thinking on this.

We can, each of us, resist the mindless panic brought on by the post-WHI media frenzy, and it's these sorts of articles that can help us make a more realistic evaluation of our risks with respect to hrt use. Further, by sharing this kind of updated, serious, and medically sound information with other women, we can help them make better, less emotional decisions for themselves. And by bringing this to our doctors, we can help them stay more up to date where they might not otherwise have the time or interest to pursue all the small studies that have, over the past decade, contributed to a much more realistic and accurate picture of hrt actions and options.

Surgical menopause boosts cardiovascular risks

2010-08-28T09:42:00.001-06:00

Update note: the study cited below, "Surgical Menopause Boosts Cardiovascular Risks" no longer seems to be available online. Nonetheless, the discussion around it remains valid and we are retaining this post for that reason.

We've known for some time now that overall cardiovascular risk rises at natural menopause to approach men's generally higher rates. This was long assumed to be the result of the shifting of balance away from the heavily estrogen-dominated profile that distinguishes (fertile lifestage) women from men. Indeed, it was cardiovascular risk that was really the underlying focus of the infamous Women's Health Initiative study: women well past menopause who had developed cardiovascular disease were put on hrt to see if it would improve their status. Sadly, no such findings resulted. Nonetheless, the generally better cardiovascular status of women on HRT as compared to women without continues to fuel research on the "critical timing" premise, that proposes that functions supported without interruption by covering hormone needs in menopause without a significant time lag are protective, but that once hormone support lags, women cannot regain that lost protection.

We also know that testosterone may worsen cardiovascular risks as it brings us closer to the male profile of risks. That's part of why the US Food and Drug Administration did not approve the female testosterone patch: it didn't improve the libido in some women (where testosterone deficiency wasn't the problem) and it did boost risks. For women with Polycystic Ovarian Syndrome, that's a special concern, since their disease is often characterized by lifelong elevation of testosterone levels. The literature is not yet clear on this hormone and cardiovascular risk

Cardiovascular risk also relates to elevated progesterone levels. A progesterone-heavy hormone balance tends to make us insulin resistant, raising both the risks of type II diabetes and cardiovascular disease in a special combined disorder called "metabolic syndrome." Metabolic syndrome is considered of the established risks of menopause.

Estrogen and cardiovascular disease

What kind of cardiovascular disease specifically? All sorts, actually. In addition the the hypertension seen as part of metabolic syndrome, hypertension alone can be a sudden-onset disorder upon oophorectomy. It saddens us to read of doctors withholding hrt from women who spike sudden high pressures when they come out of surgery out of concern for stroke risk. In fact, it can be the loss of estrogen's relaxing effect upon the walls of blood vessels that can cause this, so they're withholding the one thing that can treat the problem out of a mistaken focus on the symptom instead of the cause. Other women, less catastrophically, may find their pressure creeping up when they are advised to abstain from supplementing their hormones back up to more normative, menopausal levels or when their HRT is suboptimal.

We also know that estrogen has a beneficial effect on lipid levels and types, although oral hrts provide a different assortment of effects in this regard than transdermal do.

But today we have another small study, Surgical Menopause Boosts Cardiovascular Risks [no longer available online], that looks more closely at just what goes into that shifting CV profile with estrogen loss. Although this is a rather small study of only 90 participants, what they found was that the carotid blood vessels (major arteries in the neck that supply the brain, which are taken as representative of general vascular condition throughout the body) are narrowed in women who had oophorectomies before natural menopause age and who did not supplement their hormones back up to normative levels.

Now, they were working with living study participants, so they couldn't go slicing into these major arteries to find out precisely what had them gummed up. The assumption is that this is an atherosclerotic process, the plating out of metabolic gunk, mostly fat- and calcium-based (think about the condition of your bathtub drain: atherosclerotic placque is roughly as appealing, only with a bit less hair), on the inside of the vessels that, much like the situation in your bathtub drain, gradually reduces blood flow until it may stop it altogether or a bit breaks off and stops flow someplace else (which is what a stroke represents in mechanical terms).

But that's just an assumption, at this point. There is certainly also an element to do with that reduced vessel size/relaxation as well. Beyond that, we don't exactly know and won't until there's more autopsy/surgical data that analyzes what those vessels actually look like on the inside. Still, this is an important step because it does validate that there is actual pathology in place, and that pathology correlates to a woman's specific hormonal status.

Of note, the article concludes:

Dr. Ozkaya said, "We should think twice and discuss it with the patient, should we consider performing oophorectomy before menopause."

Now, would everyone whose doctor warned them about increased cardiovascular risk with this surgery, especially those advised that hormone deficiency would be therapeutically necessary, please raise their hands? Nope, we didn't expect so. This is the elephant in the room that never really gets discussed pre-operatively or that gets hand-wavy assurances of "you'll take this little pill and everything will be fine." Right? And so this is what women need to be able to find out on their own...or with whatever help they can find.

Should women refuse an oophorectomy on these grounds? Oh, goodness no: there are often much more dire consequences and quality of life issues represented by the pathology for which we choose this surgery. On the other hand, this does add more weight on the side of turning down the "oh while we're in here we'll just take out those healthy ovaries because you don't need them any more" sales pitch. It really all comes down to weighing risks, and that has to be done by each woman for herself.

Managing cardiovascular risk in menopause

Yeah, but most of us here have already been through the surgery. How do we manage those risks now?

First of all, by simply being aware of this, aware of the body of literature we've linked to above, that is all legitimate medical research that you can share with your doctor in discussing this aspect of surgical menopause. We need to be monitoring this risk: we need to keep an eye on our blood pressure, we need to get lipid levels checked as part of our annual checkup, and we need to be prompt in seeking actual treatment if either of these start to rise.

Beyond that, though, we can work to forestall these effects through other means, nonmedical things we can do for ourselves. That's right: we're going to talk about those unpopular topics of good diet and exercise along with weight reduction.

Right now, proponents of the high-fat/low-carb diets continue to duke it out in research studies with those supporting the so-called "Mediterranean diet." Our bookmarks account has a huge section on research and recommendations about diet: go read and make up your own mind. What you should know, though, is that diet is considered to be a major factor in cardiovascular risk and it's one we can manipulate ourselves. And by that we don't mean a week of good intentions when you give up a bowl of ice cream and really do mean to get more veggies; we mean a serious restructuring of what we eat every day for the rest of our lives. Although the site's main focus is cancer, the American Institute for Cancer Research has a lot of good, applicable material on what constitutes a healthy diet as well as tips on this next topic coming up just below.

And then there's exercise. Exercise does so very many good things for our bodies. It doesn't need to be crushing, but it does need to be regular and it does need to be at least brisk. Current recommendations from the US Centers for Disease Control and the American Heart Association are a place to start, although of course this needs to be discussed with your doctor if you have any issues that might complicate the situation. And yeah, it takes time and oh dear how do I fit that in my already busy life and maybe I'll start tomorrow yeah tomorrow for sure...we understand that whole argument because we struggle with it ourselves. The bottom line, however, is that that heart attack is going to be a whole lot more disruptive of our lives when we're spending a week in intensive care, if we happen to survive it. And, unless we get serious about prevention, that heart attack, statistically speaking, is in our future. Isn't that worth a little work to push back?

Last of all, we can't neglect the role of hormone balance in all of this. Imbalanced hormones, whether an excess of testosterone or progesterone, are likely to edge us higher in cardiovascular risk. Normative estrogen levels look as though they edge us a bit away from that risk.

That means that we need to look carefully when we're offered testosterone to make sure it's truly a situation of testosterone deficiency and we've exhausted other efforts to restore libido before we reach for this option. Using testosterone as a bandaid to cover up for poor estrogen HRT delivery: just raising our risks.

This also means we need to be cautious in supplementing progesterone. The "just because" premise of taking it, without regard for actual demonstrated need, looks less appealing with insulin resistance and metabolic syndrome keeping it company. Using progesterone as an hormonal hammer to bludgeon us into sleeping more in the face of estrogen excess: also less appealing when accompanied by cardiovascular risks.

But what about people who must deliberately induce a progesterone-heavy imbalance for therapeutic purposes? Those with endometriosis or who have a uterus are facing increased risk of endo growth and cancer if they skimp on progestogens in their HRT. Does that mean they are doomed? Certainly not, although they possibly do experience a raised level of risk and should therefor also be more vigilant about protective measures and monitoring. And they can consider, especially if they have other familial cardiovascular risks, whether they might prefer to use a vaginal progestogen to enhance pelvic circulation of that hormone without such high systemic exposure.

So does that mean if we take our HRT, we're safe? That's hard to say, but it looks as though the answer is not that clearcut. Even individuals in natural menopause experience increasing risk as their hormone levels decline, even though they are notionally still producing enough to meet their post-fertile needs. And since the level of hormonal coverage individuals with their ovaries produce in natural menopause is the situation we are seeking to emulate with HRT in surgical meno, we can assume that even if we've started taking HRT from the time of surgery and have had few disruptions in it, we still share roughly that level of risk.

And in case the question occurs to you, no, we're not advocating achieving higher-than-natural-meno estrogen levels as cardiovascular disease prevention. In that direction seem to lie increased hormone-mediated cancer risks, an equally unsavory option. So as with so many things hormonal, the middle ground of normative hormone levels and no more, along with a healthy lifestyle, seems to provide an undramatic but undeniably healthier plan.

In the news: Progestogens and lung cancer

2010-08-14T15:05:00.002-06:00

Estrogen-only therapy may not up lung cancer deaths was the headline of Reuters press release that came across our desk some time ago. According to the article, while the Women's Health Initiative Study showed that women in natural menopause taking conventional combined estrogen + progestin hrt had an increased risk for lung cancer (free signup required), women in surgical menopause taking estrogen hrt only did not show that risk elevation.

Interestingly, the research is mixed on this topic. An article "Dietary boron and HRT reduce lung cancer risk in women" published in 2008 in the American Journal of Epidemiology, stated that, based upon an "ongoing case-control study in Houston, Texas...[with]...763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT," found that "HRT use was associated with a 31% reduction in lung cancer risk."

Okay, so how do we interpret this for our use? Does this mean we should quit using progesterone?

No, this probably doesn't mean that we can't or shouldn't ever use progestogens (progesterone and its synthetic cousins the progestins), but that answer may no longer be valid across all types of use in surgical menopause, so let's look at this a bit more closely.

Progesterone is different, isn't it?

First, let's set aside the whole "progesterone is natural so it doesn't carry this risk the way progestins do" issue.

So far as we have solid information on this, this statement represents nothing but wishful thinking. We have no serious population study data that differentiates between progesterone and a progestin, let alone between different progestins. There is one study, Progesterone--promoter or inhibitor of breast cancer, that says:

Similar to other progestogens, hormone replacement therapy with progesterone seems to promote the development of breast cancer, provided that the progesterone serum levels have reached the threshold for endometrial protection.

In other words, this seems to say that if we take enough of it to do us any good, the risk is severe enough to show up. Which doesn't mean that no risk accrues to lower doses, but rather that the effect could be more subtle or take longer to show up. There's a unknown related to degree of use, here, that we can't yet fill in.

The WHI study was done with Provera, a specific progestin, and the results have not been checked in any large study against other progestins so we don't know—and analyses of the study results have pointed this out—whether this is a Provera issue or a progestin issue or a progestogen issue. Because one is taken as standing in for the whole, the media coverage and the doctors who get their continuing education from CNN will assume that it means all progestogens and panic accordingly. But each progestin has very different chemical characteristics and there is some reason to question whether this relationship with lung cancer is due to the elements progestogens have in common or an element Provera possesses uniquely. Until that distinction is made more clear, we really don't know. And until we do, we are as liable to panic and jump in the wrong direction as the right one.

So what should we do about this new demonstration of raised risks?

A lot probably depends upon how we use it

Now let's look at different categories of women and HRT use.

Women in surgical menopaue who do not have a uterus and who are taking plain estrogen, whose progesterone needs are being met adequately (as they define them) by their own progesterone production and the progestogens they acquire through environmental contamination, are shown by the WHI Study results as not experiencing this elevated risk. No one has suggested that they require hormone blockers to reduce their own progesterone production for further protection, which suggests that hormone levels appropriate to natural menopause with ovaries (which is what we emulate with hrt in surgical meno) are not presently interpreted as carrying this risk.

Women in surgical meno who do not have a uterus and who are supplementing both their estrogen and progesterone may be at an elevated risk level. As we noted above, we can't rule out risk based on the type of supplementation (progestin vs progesterone) at this time, so we can only work from the safer, more conservative position that increased progestogen exposure equates to some unknown level of increased risk.

But let's not get caught in the binary reasoning trap of research questions. This is probably not an either/or situation. That is, taking one molecule of a progestogen most likely does not slam us straight into the lung cancer risk category seen in the WHI. These women in the study who were on combined hrt were on levels of progestin designed to protect an intact uterus from developing cancer due to the estrogen stimulation. And they were on a fixed, study-mandated dose of estrogen, with no regard to their personal level of needs, especially at their age (they were women mostly in their 60s and up, taking a "standard" hrt dose for women a decade younger). So these women were being exposed to relatively higher levels of estrogen than we typically use in surgical meno if we are following the basic "as little as meets present needs" rule that is the current recommendation by the various medical specialty groups that have looked closely at all aspects of hrt use and menopause. In other words, they were taking a progestin at a therapeutic, not minimal-needs, level of dosing.

But that's not what we typically do when we supplement progestogens in surgical meno if we don't have a uterus. We take a dose only large enough to make up the shortfall between what we can produce and what our bodies need to balance out the estrogen we're taking. So the conceptual test we can apply here is that if women in natural menopause are not advised to have their ovaries removed and take hormone blockers to prevent their postmenopausal progesterone exposure, we may not be raising our risk exposure significantly when we simply mimic natural menopause with ovaries...as is the goal of surgical menopausal hrt. Now, we cannot promise you that this is entirely safe, but what we can suggest is that this seems reasonable based upon what we presently know.

But some women supplement to higher levels, and we're not sure how comfortable they should be about their risks. Who would do this? Many doctors prescribe high levels of progesterone to counteract excessive estrogen doses or to use progesterone as a hammer to bludgeon women on high or ill-fitting estrogens into being able to sleep. How high? Women who are taking 100mg or 200mg or even more of Prometrium or the equivalent are trending out of the supplemental range and into therapeutic dosing. And their risk picture is much less clear. They are approaching the level of supplementation that the WHI participants who saw that raised lung cancer risk were using, and that raises the question of whether they would be safer using some other approach for dealing with their problems than their therapeutic levels of progesterone intake. This is not a question we can answer yet, but it's probably one women should raise when they're looking at these higher progestogen doses.

And finally, the third group of women: those required to use therapeutic progestogen doses to treat some other risk. These would include women in surgical menopause who retained their uterus, or women with endometriosis. They must take more than a balanced dose to produce this therapeutic effect, and this places them right into the WHI risk profile.

So how can this set of risks be managed? On the one hand, we can look at relative incidence of endometrial cancer and compare it to the lower risk of lung cancer. Are there modifying factors? Surely familial history and smoking exposure will also play into the lung cancer side of things, yes.

Is there anything these women can do to lower their overall progestogen exposure and still obtain the benefits of therapeutically effective doses where they need it? Yes, in fact there is: use of a vaginal progestogen provides higher levels in pelvic circulation, where therapeutic effect is needed, and less in general circulation, where it is not. There's more information on this in our discussion of hrt for women with a uterus but no ovaries, as well as in a discussion of a news article about contraceptive patches.

While we don't know what "safe" is in this context, surely whatever we can do to lower our exposure risk until it's better understood is at least doing what we can to approach safer.

The bottom line

We don't have enough information yet to be able to draw any sort of safe-or-not line. We may never have this: research isn't about what we want to know; it's about what someone will fund a study to find out, and that's often dependent upon who thinks they can make money from its results. At the moment, though, this correlation between progestogen use and several types of cancer suggests that we should use only as much of any progestogen as we demonstrably need, and it probably makes sense that we should do what we can to limit our systemic as opposed to therapeutic exposure.

Should we panic and give up progestogens entirely? Oh goodness no: we don't begin to know enough to say this, and even the risk factors as they stack up don't begin to suggest that level of panic is necessary.

Should we figure that because progesterone is a natural hormone manufactured by our own bodies that it's safe? Nope, not this either: we know that our own estrogen poses cancer risks that we can reduce by controlling our exposure, and this may well turn out to be the same sort of situation. So no, the old Dr. Lee premise that you can't have too much progesterone is looking as shaky as those 1950s articles touting estrogen as the magic agent to keep us "forever young."

Hormones are active agents that are active throughout our bodies. Something this active is never likely to fall into entirely-safe territory. What we need to learn and can hope that research will begin elucidating is just what the parameters are of the risks that progestogens pose. Only then can we make sound decisions between our various risks to make sure that we're only engaging in the ones we deem acceptable for the benefits gained.

Muscle strength and hormones

2010-04-27T18:33:00.004-06:00

One of the longstanding rationales for testosterone supplementation is that it is believed to be essential for maintaining (or recovering) muscle mass and strength. It's also often been denied by the doctors of the "menopause only means hot flashes" school of thought that the sometimes crushing and always annoying fatigue and muscle weakness experienced by individuals post-oophorectomy has anything to do with their hormonal status.

But now, "Mechanisms Behind Estrogen's Beneficial Effect on Muscle Strength in Females" (free signup required to read) looks very closely into this situation from the standpoint of the physiology and reaches some conclusions that may surprise you.

Why is this important? Because physiology is difficult to write off to "oh, you're just not adjusting well to your surgery" or other blame-the-patient rejections.

This is an extremely well-written and readable report, even though the biochemistry of it may make your eyes glaze over at times. Still, it's worth it to understand their points—which you can do even if some of the terms may not mean much to you.

Basically, they are finding that the fundamental chemical responsiveness mechanism of muscle fibers is not only weakened (in strength) by estrogen deprivation but that estrogen restoration reverses this.

This linkage between fatigue/weakness and hormone levels is in keeping, of course, with many of our experiential knowledge, but doctors are trained to reject this as "anecdotal" in favor of "evidence-based knowledge." Research is, by definition, evidence-based. That doesn't mean that your doctor won't reject any research that doesn't agree with their own readings, but it's a step up the ladder.

And yes, much of what is being studied & reported in this particular article is rat-based. But in such fundamental processes, rat physiology is very much predictive of human function and it is extremely unlikely that a basic muscle fiber process would differ in humans: it's a whole different order of magnitude from the less-useful animal studies that purport to "prove" that some hormone variant "prevents" cancer. None of this is subjective: it's not anyone "feeling better" but rather specific measurable functions registering differently before and after addition of estrogen.

While the study conclusions note the pertinence expanding upon their findings might have for things like osteoporosis and, interestingly, cardiac muscle disease, we in menopause are more likely to grasp the implications for simple daily wellbeing. Just as joint aches are well within documented effects of estrogen deficiency, so now we can point to estrogen when we are overwhelmed with weakness without having to reach first for such complex diagnoses as fibromyalgia.

But wait: what about testosterone? We've been over the interplay between these two hormones in metabolic interchangeability elsewhere on this site as well as in our discussion group, and it's up to each of us individually to decide how and with what we choose to supplement. What we feel this article represents is solid, defensible support for the experience of muscle weakness in surgical menopause as being reversible with estrogen supplementation. For those who feel their estrogen needs are already well met, fine: go on to consider testosterone. But for those who count weakness in their unmet needs, this provides both solid validation of an association with their estrogen supplementation and supports a means of alleviating it, in a form that, shared with your doctor, might help educate them in this relationship.

Sexuality and surgical menopause

2010-02-27T14:05:00.002-07:00

This is, perhaps more than any other topic to do with surgical menopause, a great worry for many individuals and it is correspondingly fraught with misinformation, myths, sales pitches, and wishful thinking. As with many things to do with our hormones, you may come here hoping to find simple answers, a magic remedy to restore things as they once were (or, at least, as we wish they had been), and instead find that it is considerably more complicated than that. We're sorry to have to burst that bubble right here at the top, but if simplistic answers are what you are looking for, you will not find that here.

What we're going to do here, then, is talk through some of the things that are important to estrogen-based libido and sexual response, and then look at how we can work our way through those things to develop our own answers to the question of how we can each restore and maintain libido after our surgeries.

Anatomy

The first requirement for sexual arousal and response is having the actual anatomical structures that are necessary to experience them. That maybe sounds overly simplistic, but bear with us: we've had surgery and surgery in real life is not as clear and straightforward as those little graphics in that pamphlet your doctor gave you.

In a real belly, things are crowded together. There may be scarring from whatever previous abdominal procedures we might have had, or from the problems that led us to choose a hysterectomy. And not everyone is exactly identical. Most of us have most of the same things in fairly much the same places, but it's not exact: this person's nerve may be right here while another's is slightly over there.

Further, not every surgeon is equally skilled, especially when it comes to vaginal or laparoscopic procedures where access is trickier or where there is a great deal of scarring or other complexity to be sifted through. While they may do a fine job of identifying what they came for, the major organs to be removed, they may be less skilled at identifying and leaving intact those things that are not to be removed.

And, finally, not every surgeon feels that surgically menopaused individuals should have their sexuality preserved. Whether they see it as a personal crusade to help reduce the moral affront of non-reproductive women enjoying sex or whether they genuinely believe they are saving us from the indignity of having what they view as shameful feelings, they may make a decision for us that reflects their own values, without consulting us, and accordingly be less than scrupulous about preserving those nerves and other structures required for sexual response.

For most of us reading this, it may be too late to do anything about our anatomical integrity. Certainly if you are still in the preoperative planning stage and reading this, you should discuss preserving needed sexual structures with your surgeon, frankly and fully, to be sure that you feel confident that your surgeon will follow your wishes in this regard. If he does not seem willing to do so, well, there are many other surgeons in the world.

What if you are postop, though, and wondering about this? This is not the first thing to work on because, let us hasten to assure you, this is not a common outcome of a hysterectomy. It is more likely to be so for a more complex surgery that affects more than "just" removing the uterus (say, removal of extensive endometriosis with heavy scarring, or a radical hysterectomy for cancer). It's probably not the first thing on the troubleshooting list. But it is a possibility that will ultimately need to be considered if hormonal balance measures are ineffective. It's an aspect that many people skip right over, but since it's a make-or-break part of the whole situation, we have to keep it in mind even when we turn our efforts to the more common situations first.

Systemic estrogen

So if the anatomy provides for the basic mechanical equipment for sexuality, it's estrogen that powers it.

Surprised? Thinking that we were going to jump right ahead to testosterone? Nope. That's the single most common error in troubleshooting libido and while we'll get to testosterone eventually, what we're doing here is setting out a hierarchy of needs, each of which builds upon the other in providing for full sexual function. And it's estrogen that really powers full sexuality in estrogen-dominant individuals.

We rely on estrogen to help things throughout our body function normally. Estrogen is so fundamental to our bodies that even cis-men produce and require some estrogen for normal health. While we no longer require enough estrogen to support fertility once we reach menopause, we do still have other, non-fertile needs that must have estrogen to function. And many of those needs specifically relate back to libido.

You can read elsewhere on this site about how estrogen is needed to support normal brain chemical balance. If our brain's needs for estrogen are not met, we are subject to disturbances of mood and thinking and sensation that probably won't let us relax into feelings of arousal and sexuality. So before we can experience libido, we have to have healthy brains that can feel inclination and completion.

Other areas of our wellbeing are equally important to a background level of comfort that will let us even begin to think about engaging in sex. Those of us with low estrogen levels often experience crushing fatigue or joint pains, or lack of sleep due to menopausal symptoms may sap our enthusiasm for, well, anything. To try to force sexual interest when we can barely stand to be inside our bodies is going to be a struggle, and that's not what healthy sexuality should be. No matter how much we or our partners want us to resume sexual activity, it shouldn't be a grit-my-teeth-and-carry-on sort of thing.

And estrogen is required for one more aspect of sexuality, and that's feeling like a sexual individual. Whether you call it femininity or sensuality or desirability or whatever, we need to feel that physicality is desirable. That wholeness of individuality and sensation requires estrogen, and without it, the tenderness and mature sexuality we are looking to regain simply is not there.

But what if you are taking hrt already—isn't that taken care of, then? No. Taking hrt does not mean that you are effectively delivering hormones to your body or that you are delivering the right hormones in the right amounts. HRTs are much more individual than that: every hrt works for somebody, but each of us may find that only a certain few hrts really work well for our own bodies. If this concept is new to you because you've started reading this site here, please use our table of contents to explore the rest of the basic hormonal/hrt background we've provided here—especially the "basics" section at the top.

If you are having symptoms of hormone imbalance, then, or if you have unmet hormone needs apparent despite being on hrt, you may not be providing the fundamental underpinnings for sexuality. Just as we must have the physical structures to actually undergo sexual arousal, we must have our basic systemic hormone needs met well enough to desire sex and to feel arousal. And it is estrogen that provides that hormonal foundation.

Vaginal estrogen

The single most common barrier to full menopausal sexuality is lack of vaginal estrogen. This is where the anatomical structures and our hormones come together, directly at the seat of sexual sensation. Without estrogen here, it's as though the main switch controlling our sexual responsiveness is turned OFF.

Our genitourinary tissues (vagina, bladder, and all their associated nerves, blood vessels, and supporting structures) have a high requirement for estrogen. Without enough estrogen, these tissues lose elasticity, lubrication, sensation, and protective immune response, and they become pale, fragile, thinned and gradually lose function. This situation is called vaginal atrophy and, depending upon the source you read, can affect from 50-75% of all women in menopause, surgical and natural alike.

If you've never heard of vaginal atrophy, don't be surprised: you have plenty of company. Despite this being ridiculously widespread, it's a silent epidemic of deficiency that is ignored by both individuals and physicians. Why? Because many of us are taught to expect that menopause will mean they "dry up down there" and lose sexual interest. They may be embarrassed to raise this subject with their doctor. And their doctor may be equally reluctant to bring up the topic and feel that he's done his job by vaguely inquiring if "everything is alright." While efforts are being made (free signup required to read) within the health care community to raise awareness of the need to deal with vaginal atrophy, we need to do our part by opening the question with our doctors.

But what if we're already taking hrt? Doesn't that take care of the problem? No, not necessarily. At today's lower doses of hrt, we're trying to balance risks and benefits by using just the bare amount that meets our basic systemic hormone needs. That amount, in turn, is very likely not going to be adequate to fully nourish our genitourinary tissues.

The good news about vaginal atrophy is that it is very easily diagnosed by symptoms or visual inspection by your health practitioner. Further, it's easily and very successfully treated with some form of vaginal estrogen supplementation (they all work well, so it's a matter of choosing the method you prefer and can afford). This gives those local tissues a boost without derailing our systemic estrogen balance, and because the dose needed is very very small, it's something that is accessible even to those who must restrict systemic estrogen levels in order to control other risks.

It takes some weeks to fully reverse the effects of low estrogen on vaginal tissues, depending upon whether you choose a maintenance dose product or a treatment dose product. And it typically requires ongoing low maintenance doses to keep those tissues healthy—this isn't a "treat once and done" situation. But once good health is restored, return of sexual sensation and desire often follow. No matter what else we may do to enhance sexual arousal and response, they are unlikely to work until we have healthy genital tissues to experience them. You can read more about vaginal estrogen needs and how to meet them in our discussion of vaginal dryness.

Testosterone

Nothing has greater chic in the hormone world today than testosterone. Estrogen is still on shaky grounds following the massive fear campaign kicked off by superficial interpretations of the results of the Women's Health Initiative Study, despite more recent efforts to provide a more balanced consensus. Progesterone continues to be rejected by many doctors because they fail to understand its uses outside the uterus. But testosterone is in that golden spot enjoyed by estrogen during the middle of the last century, where it is evoked as a magic elixir to cure everything that imbalanced estrogen hrts cannot and not yet overshadowed by any significant sense of risk. Although risks have been demonstrated by medical research, because they have not been popularized in the media the way estrogen risks have been, they are generally unacknowledged by doctors and their patients.

Let us state right here that we are not opposed to the use of testosterone and that we are profoundly grateful for pioneering research done on the topic. Just a few decades ago, it wasn't even proven that women produced their own testosterone and that it had a role in female hormone balance. But much of what was written then is overly simplistic in the light of what we know today about hormone needs and risks. Testosterone can be an answer, but it is not, alas, the invariable answer.

Early research showed that individuals in menopause often had low testosterone levels and when these menopausal people were given testosterone supplements, they scored higher on many measures related to sexual function. As more of us used testosterone, it was also discovered that many of their lingering complaints about lack of energy and strength, even on estrogen hrts, were resolved. So, magic elixir, right?

No. At the same time, more detailed research was not only pointing out the cardiovascular and cancer risks that testosterone use might involve, but it was also showing that those who were low in estrogen were using their testosterone not to do testosterone work, but as raw material to convert to estrogen. In other words, for individuals who have not achieved good hormone balance on their estrogen hrts, testosterone is just another source of estrogen and the improvements that they experienced were due to their estrogen needs being more fully met rather than any effect specific to testosterone.

So how does this fit into working on libido loss? The very important lesson we can take from this research is that until we know that our estrogen needs are fully and satisfactorily met, we cannot know whether or not we are going to get any testosterone-specific benefit from the addition of testosterone to our hrt.

Yes, we know this flies in the face of what compounding pharmacists, who insist they can fix every single hormone imbalance at once, will tell us and it certainly is not what the pharmaceutical companies who manufacture testosterone products want us to believe. That is, however, why the major professional society of endocrinologists, the doctors who are the specialists on hormones and how they function in the body, have said in their position paper on using hrts, that

Androgen deficiency should be diagnosed only in women with adequate estrogen status.

But wait—does that mean that there is no role for testosterone in treating libido? What about all those glowing press releases about that new patch and how it helps so many individuals? The US Food and Drug Administration held off approval of that patch in the US because of concerns about risks, even though it had been approved and for sale for some time in the EU. As of 2014, however, not only has the US FDA rejected the patch licensure application, but Intrinsa, the European patch, is no longer on the market there (although the reasons for the withdrawal have been questioned).

Of course there is a role for testosterone in menopause: if there were not, we wouldn't produce it ourselves. But don't be swayed by those who want to sell you something: that's really all about them, not you. For all of the individuals who responded favorably to the tests for that new patch, there were also those who did not. In fact, testosterone supplementation is effective only for a percentage of women, no matter how it's administered.

We need, then, to look at those who didn't respond just as much as those who did. And, based on research and interpretation of our understanding of hormone physiology, it looks clear that the simple answer is that if a woman doesn't need more testosterone, more is not going to help her. Doesn't that sound a lot like what we say about the other hormones? Exactly: with testosterone, as with every other ovarian hormone, we need only enough to meet our needs; anything more only adds to our risks, not our benefits. If we have enough testosterone already (or would have if we weren't using it to make estrogen out of), more isn't going to make it work any better.

In fact, more testosterone not only raises those risks mentioned above but doesn't really provide for the sexuality we're looking for, even though it may increase our urges. Here's how one of our message list members who was working on their libido with testosterone described the difference:

With testosterone, it looks like it addresses one part of the sexual libido thing — genital stimulation and desire for it — but not the desire for intimacy.... I can vouch for this statement from personal experience — for me that sums up how I felt 100%.

Pulling it all together

Yeah, yeah, you may be saying, but how do I use all of this to troubleshoot my libido? Let's look at that now.

Based on documents like that endocrinologists' position paper and the experiences of women like you who have come to our discussion forums to work on these issues for themselves, here's the order of addressing our hormone needs that seems to be the most efficient and likely to work.

Meet systemic estrogen needs. If we are not fully meeting our needs, we don't have the basic foundation to experience sexuality. For individuals who do not want to or are not able to take hormones, it's important to choose an SSRI (if that's being used in place of hrt) that does not have a libido-suppressing effect. Only once we are at a systemic and brain balance are we ready to work further on restoring libido.
Meet vaginal estrogen needs. If you have dryness or burning or other genital symptoms, you may be suffering from low estrogen to that area. Even if you are not, if you are taking systemic hrt you may not be fully nourishing those tissues. So the first step in troubleshooting this aspect of libido is to ask your doctor for an exam (we're talking visual exam—not a painful or mechanically invasive test) and discussion of vaginal estrogen needs, and raise the question of whether or not you might benefit from some vaginal estrogen. Yes, this may be embarrassing. But many doctors are very willing to discuss this topic with you even if they too are not sure how to open the dialog. So take that first step and you may well find that things are very much easier after that.
Vaginal estrogen needs are critical to sexual function and are very easy to supplement successfully. For many, this has been the step that has restored sexual function. Yes, just this simple.
Meet testosterone needs. This comes third on our list because it will be ineffective if the other two needs are not met first. And rather than just launching into trying testosterone, this is where we'll reverse our usual stance that questions the value of hormone level tests: it's a good idea to have our circulating blood levels of free testosterone tested. It's a simple blood test that your doctor can order done by a lab.
While the normal levels are a range, not an absolute, they will give you some guidance as to whether or not you are near adequate in production. Many of those without ovaries are perfectly capable of meeting their menopausal testosterone needs by adrenal output, so it isn't unusual to find that supplementation isn't really needed to reach normal levels once it's not all going to produce estrogen. If we have normal testosterone levels, adding more testosterone is more likely to push us into excess—with its associated significant health risks—than to improve the action of testosterone. So it makes sense that we might consider testing first and only bother with supplementation if we show a demonstrated testosterone shortfall after our estrogen needs are properly met.
It's also a good idea, because it relates to our cardiovascular risk profile and how testosterone raises those risks, to have our cholesterol and other blood lipids checked when beginning testosterone supplementation. Treatment of elevated levels may be required in order to use testosterone safely, so it's easier to get this additional blood test up front than to find out only after we've had that heart attack.
We're not going to spell out the different testosterone options and how to use them, since they vary from country to country and to some extent are personal preference. There's more on that on our various testosterone and hrt pages, which you can find in the table of contents.
Consider whether there has been anatomical damage during surgery. This is the last step in the process. If we find that we've got our estrogen needs well met, both systemically and vaginally, and we find that either we don't need more testosterone or that the testosterone we take doesn't make enough difference, then we need to consider whether we have had some sort of damage during surgery that is preventing us from sensing or responding to sexual stimulation. This is a complicated topic, and may require visits to more than one doctor. As a general rule, taking this up with the surgeon who performed our hysterectomy is often not particularly helpful—this doctor may just feel that we're attacking their competence or planning a lawsuit, and they may respond defensively, putting the blame back on us. Since blame has little effective value at this point, that is not an especially satisfying strategy for solving our problem. Instead, many individuals find workups from specialists on pelvic floor medicine helpful, opening up referrals on to neurologists or other surgical specialists depending upon the specific problems identified. It is possible to have some surgical damages corrected, so keeping an open mind going into this process is important: it can take time, but it doesn't mean that you won't ever regain sexual sensation.

So, a long discussion of possibilities and steps, and that's probably not the sort of answer you were hoping for. We'd all like to believe that the magic, whether it's testosterone or some obscure herbal remedy not-available-in-stores, will instantly restore us to the sexual appetites and capabilities of an eager 20-year-old. But in fact, as so many things to do with surgical menopause, it's more complicated than that and there are no universal answers that work for every one of us. Still, the things we have outlined above can help you work through the possibilities in an orderly fashion that has worked for many. Whether your own answer is in estrogen or testosterone or in surgical repairs, there probably is a good answer out there for you. It just takes some work and experimentation and careful recording in your meno journal.

I think I'm allergic to hormones

2010-02-05T14:22:00.002-07:00

You probably aren't. Think about it: you have had much higher levels of ovarian hormones in your body since puberty. If you were really allergic to them, you'd be more or less dead by now. Seriously, true allergy to one's own hormones is an incredibly rare condition. While low levels of estrogen can make our immune system more prone to taking offense at many previously-tolerated substances, that's a different situation entirely from having an allergic reaction to the hormones our hrt contains.

But I took HRT and it made me sick!

It's important to try to understand what aspect of any given hrt didn't agree with us rather than just writing them all off. By considering the matter in greater detail, we leave ourselves other avenues to pursue in meeting our hormone needs. So let's look at some of the things that cause unpleasant reactions.

True allergy to an ingredient

There are other things in all of our hrts besides the hormones they deliver. Some individuals are in fact allergic to the coloring agents in pills or the adhesive on a particular patch or the vehicle in which a cream hrt is prepared. One hrt that is a particular problem for those allergic to peanuts is Prometrium, which uses peanut oil as the vehicle in its gelcaps.

If we already know we are sensitive to an ingredient or we break out in an ugly rash or suffer difficulty breathing, then we can rightly suspect that we need to work around an allergic response. But some detective work may be needed to determine just which aspect is causing the problem. All retail hrts list their full range of ingredients on the prescribing information package insert, including the "inactive" ones that color and bind them. Any compounding pharmacist can provide a woman with a similar list for any custom hrt they prepare for her.

If we take a pill, for example, and develop a reaction, rather than assuming we can never take any hrt ever again because it was the estrogen we responded so unfavorably to, we might well invest some time looking at what is in that particular hrt and then searching out a comparable one (by using our estrogen hrts page, for example) that doesn't have the same ingredients. We list the inactive ingredients of every major brand-name hrt on that page, to make it easier to compare them. If you're using a generic, though, you may have to do some additional research by contacting your pharmacist to find out what the brand is and what the additional ingredients for that generic brand are. Allergies are something a pharmacist typically takes seriously, so they can be a good resource for tracking down what's in what we're taking.

If our problem is with a patch, it's important to understand that in each brand of patch, the adhesive is the delivery system and for it to be patented, it must be different from every other brand of patch. That means that no other patch will exactly replicate the one that has just given us problems, and so by switching brands, we stand a good chance of leaving that problem behind. Again, if you're working with a generic, identifying it and its additional ingredients is something your pharmacist can help you with.

In other words, for every hrt, then, we can do a little detective work and find an alternative that leaves out potential allergens.

As a side note on ingredients and allergies: don't expect your doctor to know much about hrt ingredients other than the hormone they deliver. It's just not important to them in most prescribing situations. This information is, however, recorded in the drug information, where it can be checked in such references as the PDR, product data sheets (which are linked from each estrogen or progestogen (or UK) brand here on the site), and through your pharmacist (who can also contact a manufacturer for you if there is a question that is not answered by the product data sheet).

What if all of the retail brands in our chosen delivery method contain this agent? Don't forget that compounding pharmacies can often prepare a similar hrt (in terms of route and active ingredient) that can leave out specific problematic ingredients. Just because we have allergies doesn't mean that we can't use any form of hrt: we just have to do a little more work getting it.

But I hated the way the hormones I took before made me feel

One special case we see often on hrt discussion forums is the concern voiced something like this:

I took birth control pills and they made me feel awful so I know that means I can't ever take hrt.

That's a really common misconception, so let's lay that one to rest right now.

Birth control pills contain larger amounts of hormones than menopausal hrts, and they typically contain both a synthetic estrogen and a synthetic progestogen (progesterone-like compound). Both of these agents are not human-identical in molecular structure, which means they are processed by the body differently from our own hormones. That's the idea with birth control pills: we don't want our bodies to use them for anything other than over-riding our own ovaries to prevent ovulation. But that very misalignment with our own chemistry means that we may respond differently to these agents than we do to our own estrogen and progesterone. HRTs contain lower doses and in many cases more human-identical hormones, so they are processed differently from oral contraceptives and they have different effects from them. Because of this distinction, then, gently-handled hrt is usually an entirely different experience from using the big hammer of oral contraceptives.

But there are many other ways an hrt can disagree with us that aren't true allergies.

Route-related effects

Some of us have skin that doesn't especially like to be sealed up under a patch, any patch. Some of us have digestive disorders or liver conditions that may mean that adding the burden of processing an oral hrt may cause uncomfortable symptoms like nausea. Individuals with inflammatory bowel disorders or endometriosis, for example, may find that vaginal hrts cause too much local stimulation and can be associated with diarrhea or cramping. All of these kinds of things are really due to the way we're putting the hrt into our bodies, not the actions of the specific hormone they contain.

In many cases we already know that we have these issues, and so when we select an hrt to try, it tends to make sense that we should choose routes that don't conflict with pre-existing problems. If your doctor isn't putting this together when he prescribes your first hrt, don't hesitate to mention something like "since I already have digestive issues, I'd really prefer an hrt in some other form than a pill." You know your own body than anyone else, so you can—and should—use that knowledge to head off possible problems.

What if you don't know? Then we have to reason our way to what might be the issue. This isn't necessarily complicated: if we have horrific nausea, it really makes sense to try to get around that by switching to a non-oral hrt. Just understanding that every route of delivery has an effect on our bodies is part of the key to not writing off hrts entirely, but focusing in on what part of the hrt delivery is being problematic.

Dose-related effects

These are the most tricky to grasp when we haven't yet been introduced to the idea of needs and hormones.

Hormones are active substances that fulfill certain needs in the body. We only need so much hormone work done at any given moment, however. If we don't have a great enough supply, some hormone work goes undone and we experience symptoms from what isn't covered. We all are familiar with one effect of undone hormone work: lack of thermoregulatory stability, which results in hot flashes. But there are many more effects of inadequate hormone supply, some of them quite unpleasant.

We need to differentiate these from negative effects of hrts, however, if we are to work effectively with our hrts. It's most frustrating when we take an hrt that doesn't deliver to our systems and we experience these effects, since it seems as though we're making ourselves worse with the hrt. But if we look at the effects of low estrogen, we can get a sense of the difference.

Now, if we take an hrt that contains an excess of hormones, such that more hormone work is being done than we need right then, we also develop symptoms. Again, while these can be very unpleasant, they don't mean that the hrt or the hormones are somehow wrong for our bodies; it just means that there's an excess of that work being done. This would include things like fluid retention and swelling, a normal effect of estrogen but one taken to an excessive level when our dose is too high. In this sort of situation, backing off on our dose until we reach a supply more closely aligned with our level of need will allow these symptoms to abate and a more comfortable "fit" with our hrt achieved.

There's lots of troubleshooting involved in this process and sometimes it's really not too clear which way we're trending. We spend a lot of time on our discussion forums discussing this sort of thing. What we're introducing here is the bare outline of the concept, roughed out so that you know that this can be one source of problems; it's not really a full exploration of the kinds and extent of problems that can occur with hrt dose mismatched to needs. We just want you to know that this can happen, and why it can be so unpleasant...without really being an allergy.

What's the best way to get a perfectly even hormone delivery?

2010-02-05T14:03:00.006-07:00

You can't.

No, really. It's a myth. Yes, we know the notion that this will solve all of our hormonal ills is a very popular, very prevalent theme in hrt discussions online. But it's really neither possible nor necessarily desirable.

Shocking, no? Yes, we do understand that the ups and downs of the various delivery routes can be problematic, causing all sorts of unpleasant symptoms. But that doesn't mean that the attempt to do away with them by taking ever more frequent ever tinier doses is going to work. That's right: even if we were to walk around with a constant IV drip of estrogen, we still wouldn't eliminate fluctuation.

That doesn't mean that we can't smooth things out, but it does mean that we need to look into the situation a little more intently to determine what exactly it is that needs to be fixed.

Life isn't a perfectly stable system

To begin with, nothing around us is perfectly stable. Today we are stressed by a deadline at work; tomorrow we will have a cold; the day after that is our birthday and we'll have that surprise party even though you know how we feel about surprises. Everything around us changes and our bodies are built to cope with that. We need that ability to cope, because there will always be something out there, a stress good or bad, or even the relief of stress.

Our interactions with the world affect our hormone supplies as well as the demands upon them. We eat foods that contain estrogens, either as plant estrogens or as hormones given to commercial meats or as estrogenic pesticides applied to plants and coating them or eaten by the animals we then go on to eat. We drink water supplies into which every day vast quantities of drugs and pesticides are flushed and, because their content is not legislated, we never see test results to show us how very many things are still in our "clean" water. Every molecule of the hormonally-active compounds we consume becomes a part of our hormone reservoir, a reservoir that changes from moment to moment, hour to hour, day to day.

Neither is our body

Our endocrine system (that portion of our physiology to do with hormonal regulation of various functions) is itself not a static system.

First, our bodies need to be able to keep things running in that ever-changing world we live in. We need reserves to allow us to cope, to ramp things up when we're facing stress and to ramp things down when stress eases off.

And we need to maintain cycles of our own. We may have been accustomed to the cycles of fertility, but there are many more cycles in our bodies. One of the most important is our daily cycle of sleep and waking, the latter encompassing various stages of alertness and, well, not so much.

Our estrogen is a critical component of our daily cycle. Our levels naturally are highest in the morning, fall gradually during the day and evening, and reach their lowest point around 4 or 5 am. This cycle keys in with with many other hormone cycles, including that of melatonin, another hormone that helps regulate our sleep cycle. It also interacts with thyroid hormone as part of our metabolic regulation. If estrogen levels were completely static, our whole system would come adrift from this important regulatory relationship. And if our hrt were absolutely continuously stable, we'd spend most of our time with either too much or too little to meet our bodies' demands during our daily cycle.

Change, then, is both an inescapable part of both internal and external hormonal regulation and response. But that doesn't mean that it doesn't pose challenges when we do it to ourselves with our hrts.

But the ups and downs are killing me!

The problem is that our body wants to regulate things so we stay on a fairly even keel amidst all of these changes. We work hard, all the time, to do so. When that doesn't happen, of course, the resulting temporary imbalance and the shifts of it coming and going all cause symptoms that can range from annoying to devastating. And it's a feature of our response to change that the greater the fluctuation, the greater the response to it will be.

The most comfortable hrt, then, is going to be one that eases into our bodies with the least disruption, is taken at a dose that lasts long enough that its falling effectiveness meets the rise of the next dose without either great troughs or peaks, and provides a reservoir of hormonal potential to get us through the times of day when we must respond to a need for greater hormonal activity. And as it turns out, none of that actually requires anything like a completely continuous supply.

Minimizing the ups and downs due to uptake

There are two important facets of getting hrts into our bodies. First, they have to physically get into our systems and, second, they need to impact our circulation in a fairly tolerable manner. Both of these factors can present us with problems when hrt characteristics are a mismatch for our personal capabilities.

In dealing with the first problem, we need a delivery method that our bodies can absorb smoothly and reliably. A patch that is stuck now and flapping later isn't going to do that; instead, it will provide us with a roller coaster of ups and downs. Oral deliveries may not work reliably for all women. A gel might be sweat off on the days we go to the gym. All hrt delivery routes have ways they can fail to work smoothly, and so when we're not happy with how a dose is taken up by our bodies, we need to take a close look at just what kinds of interference we might be experiencing at this very basic level of delivery.

But it's not enough to get those hormones into our bodies effectively. We also have to weather the rise in circulating hormone levels. Each hrt will create a slightly different uptake curve if you plot out the amount of hormone in our blood over time. A patch will start delivering fairly rapidly, but if the previous patch was exhausted and our hormone support from it had dropped, even the small dose delivered by a patch will be seen as a sharp uptick by our bodies. Some individuals find that the rapid absorption of a whole day's transbuccal dose doesn't dissipate rapidly enough to prevent being hit by something of a slam.

Each hrt has its own time and type of uptake. When we are troubleshooting these, we can look at alternatives that might perform differently. For example, if a cream transdermal dose seems to provide too abrupt an uptake to be comfortable, perhaps the slower uptake of a gel would be more gentle while still otherwise providing a transdermal profile of effects.

But an often-neglected aspect of uptake has to do not so much with delivery route but what specific hormone we're delivering. When we're taking estradiol, we're using the active form of the hormone. If we dump a day's estradiol into our systems at once, we may have trouble moving quickly enough to convert the portion of it that we don't need to have active at that exact moment into the inactive reserve form, estrone. If this is the case, our dose might give us a fierce headache or palpitations or excessive jumpy nervousness.

For those who experience this problem, it’s possible to get around this effect somewhat by switching to an hrt that contains some or all estrone. That way, the net total hormone support delivered in a dose cycle is still provided, but the initial slam of excessive activity can be dodged. Not all of us experience this problem, but for those who do, this can be a highly productive direction to explore. This is especially true for those who suffer from migraines when they take estradiol, perhaps because the two estrogen versions affect somewhat different areas of the brain.

Minimizing the ups and downs due to duration

If the dose of hrt we take doesn't last until the next dose is taken, our hormone support will taper down far enough that both its decline and the rise of the next dose's uptake will cause uncomfortable fluctuations. While users often address this gap by trying to take smaller doses more frequently, that often doesn't provide a fully satisfactory coverage, not to mention becoming increasingly impractical.

A common misunderstanding of the concept of "half life" often drives this attempted solution. "Half life" in medical terms is simply how long it takes for half of a dose to be metabolized. The fact that a dose is half gone, however, doesn't mean that another full dose is needed; it only means that the body has taken its normal steps to process our hormone supply as it's used to meet our present needs.

If a dose interval is meant to be a full day, then, it's appropriate that the half life be 12 hours. That means we'll have used up most of yesterday's dose by the time we add today's. Yes, that's some up and down, but our body can handle a fair amount of variability through its own storage and retrieval mechanisms if we're not shorting ourselves down too far between doses. The other direction, taking a new dose before we've used up most of the last, only takes us into excess...and excessive risks. In fact, many individuals tune their dose exactly so that they do feel a bit short as the next dose comes due or so that they do have a hot flash or at least warm spell at that 5am low point in their daily hormone cycle, just so that they know they're skimming along the edge of "lowest effective dose."

So in practical terms, if an individual feels as though they're running out far too soon, they might do more good by re-examining their total dose amount and consider whether taking more would make it last longer and round out that dose period. Taking it more frequently only speeds up the cycle of ups and downs and doesn't really improve its coverage.

Minimizing the ups and downs due to reservoir

There's another factor, beyond simply how long the dose lasts, and that is the form in which it lasts.

Yes, the measured amount of our total hrt-provided intake goes up and then down, but focusing on that alone misses the fact that our overall hormone capacity is not represented by just one form. When is taking estradiol, an individual's body will normally move quickly to convert any excess beyond momentary need into estrone, which will exercise less activity. In the course of the subsequent dose interval, that estrone will gradually be converted back to active estradiol as current demand requires, throughout this period, to do more estrogen work.

We’re not sure of the physiology behind this, but some women seem more comfortable when they have a considerable reservoir on board. Now, that’s not an excess we’re talking about; we only mean the sort of buffer that a day’s dose provides. Those for whom this is the case often feel edgy and stressed, never quite comfortable in their bodies, on trickle-dosed hrts (patches, pellets, even gels), as though something isn’t right even though they may have lab tests that put them in an ostensibly normal hormone level range. Unfortunately, this is often the sort of situation in which they move to trying to manage their hrt levels even more closely—something that is actually moving in the wrong direction. Switching to daily dosing, which allows their bodies to regain and manage a reservoir to meet their fluctuating needs in a more natural process can help alleviate that problem and provide a better fit between hrt and how their body best functions.

This is vague. Also, confusing.

Yes, we know. We’re getting into the more subtle aspects of hrt “fit” here and there are no real rules, no body of research knowledge. By standard medical thinking, all pharmaceutical hrts must work exactly alike and if there’s a problem, it’s somehow with the patient.

But in the decades we’ve been watching hrt use and talking with women about what they’ve tried and experienced, these seem to be common trends and the strategies that seem to have good, durable results for dealing with them.

These aren’t recipes, however. We need to think about the ways our current hrt can be ill-suiting us and we need to know enough about hrts to know which ones hold different characteristics. This is way more subtle than the situation where if we try one patch at one dose and aren’t happy, our only option is whatever oral hrt our doctor most often prescribes. Our hrt pages here can help you with some of this (they're arranged by hormone, so check the Table of Contents for links). If nothing else, we hope that this will help keep you from wasting a lot of time and effort adding and subtracting bits of patch every hour during the day (yes, we’ve actually read accounts of women so desperate to get that impossibly even hormone state that they’ve tried this). And encourage you that there are some fairly subtle things that can be done to manipulate our hrts’ effects to make them fit better.

As ever, we’re more than happy to discuss this in greater detail on our forums. While we can’t provide answers for everyone, we can often ask questions to help them discover their own best answers.

Progesterone: do I need it or not?

2009-12-31T16:59:00.007-07:00

This is an eternal question wherever individuals in surgical menopause are discussing their hormone needs, and it can be difficult and confusing to figure out the answer.

There are actually a number of issues here, and it's important not to confuse one with another. Things get trickier because when we discuss this hormone with our doctors, we often end up in an apples-and-oranges situation where each of us is actually talking about different things. Add to that a massive marketing campaign and you can get deeply conflicting answers depending on whose version you're reading.

Let's see if we can clarify the situation by looking at the typical uses of progesterone and how they relate to us in surgical menopause.

Estrogen "dominance" and the infamous Dr. Lee

Search around the internet and you'll find that Dr. John Lee seems inescapably tied to any discussion of progesterone. Read some of the sites where his work is featured and soon you will believe that you suffer from estrogen "dominance" and that all your ills can be cured by the application of progesterone, the more the better.

This is pure sales pitch. Just like that pitch for that "optional" coating under your car that means more profit for the dealer than you, so this originally was a sales campaign for Lee's books and products. But there's one major problem here: estrogen "dominance" is an invented condition and even if it were real, it wouldn't apply in surgical menopause.

Where this progesterone issue does have real-world meaning is in natural perimenopause. Although the term "estrogen dominance" is purely a made-up marketing ploy, in fact those in natural perimenopause typically experience a decline in progesterone production before they do in estrogen. This leaves them at the mercy of their wildly swinging estrogen levels, which are what causes many of the symptoms of the perimenopausal transition. Supplementation of progesterone during this time can help even out those swings by using the normal inter-relationship between these two hormones, estrogen and progesterone, to dampen them down.

So while there's no "disease" of "estrogen dominance," the entirely natural fluctuations of perimenopause can be smoothed by bringing these two major hormones back into better balance by covering that relative shortfall in progesterone until estrogen production falls enough to be in better balance with one's own menopausal supply. That's a temporary situation, albeit one that typically lasts several years.

But that's not us in surgical menopause.

For us, the transition happens in the operating room and although we have a period of getting settled in on our new post-ovarian needs and supplies, we don't have that perimenopausal mismatch and upheaval of declining ovaries. Even if we were in natural perimenopause before surgery, that situation ends when we make our transition to full menopause: it doesn't matter if then we were imbalanced in our ovarian hormone output; now we are wholly reliant upon post-ovarian supplies and we have an entirely different level of needs we're meeting with that supply now that we're in in menopause.

So no matter what you personally believe about Dr. Lee and his catchy marketing terminology, if you are in surgical menopause, this argument simply doesn't apply to you.

Uterine protection: it's why your doctor says no

Many of those new to surgical menopause have read or heard about progesterone supplementation or have taken oral contraceptives during their fertile lifestage, which leads them to wonder: don't I still need progesterone as one of my hormones supporting good health? And when they ask their doctor and receive a resounding NO, they're very confused.

Yes, our bodies do still use and require progesterone in surgical menopause.

The issue your doctor is addressing, however, is not this basic one of hormone physiology. Your doctor is instead answering the question of whether or not there is a medical reason for him to prescribe progesterone supplementation for you.

The primary USFDA approval for prescribable forms of progestogens (a group term used to describe the human hormone progesterone plus its synthetic versions, the progestins) is to prevent excessive stimulation of the lining of the uterus by estrogen, a situation that can lead to development of cancer. Doctors are for the most part required to prescribe drugs for the uses for which they are approved, which is taken by many doctors to mean: if it's not approved for a use, that means that it doesn't work for that use. By medical reasoning then, the only thing that progestogens can do in the body is provide uterine protection and, clearly, after removal of our uterus we certainly don't need that. Hence, we don't need a progestogen.

Why won't your doctor answer your question about hormone needs rather than prescribing? Because prescribing is what doctors do: they diagnose and prescribe medical treatments for disease states. What they don't do is teach us about physiology, and so it's up to us to recognize that we're simply not communicating ion the same terms in this situation. Instead of asking do we need it, then, we need to be prepared (and there's more on this below) to support our request that we give it a try—an entirely different question.

But I got a test done and it showed that my levels were very low!

Because our bodies can—and do—convert our ovarian hormones one into another, we can't just look at any single hormone level and understand the full situation. Progesterone levels in the blood don't really measure how much progesterone activity is going on in our systems; they just measure how much is circulating in our bloodstream at that particular moment.

The most common situation in which we experience this apparent shortfall arises is early in surgical menopause. That's when we are working to get our new hormone needs balanced out against hrt supply but we're not yet fully covering our needs with hrt. When that happens, our bodies place a priority on estrogen and use every resource available to produce it. One of the most important resources we can turn t for that use is our pool of progesterone, produced by our adrenal glands from more basic constituents. Because estrogen is a higher priority, we'll stint our progesterone needs—or anything else that progesterone can be used to manufacture (and there are a number of them)—in order to come as close as possible to meeting our estrogen needs.

Obviously, when this is going on, our estrogen needs are, we hope, close to met but our progesterone will measure low. Beyond this, our system is stressed because we're in a crisis mode, pulling from here to patch up there. But if we "read" this situation as primarily one of a lack of progesterone, though, we're likely to just go on propping up imbalance by adding more progesterone to support this misalignment of supply and demand...and stress.

If, instead, we understand this cascade of hormone priorities and supply, we'll also understand that the recommendation of the American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause (free signup required to read) makes sense when it specifies that we need to work on meeting our estrogen needs with estrogen hrt as well as possible before we even consider whether or not we need to supplement any other hormone.

When we supplement our estrogen as well as possible, then we no longer need to prop estrogen up with progesterone (or any other hormone). Once our estrogen needs are covered and we have recovered from the stress of skimming progesterone for that purpose, then, and only then, can we decide whether or not we need to supplement our progesterone. Only then does a progesterone level even begin to speak to the actual state of our progesterone capability.

Let's repeat that because it's so important: before our estrogen needs are fully met by our hrt, we simply can't use the results of a progesterone level because that level just plain doesn't measure our actual progesterone capability or needs: it only measures the stress put on our systems by imbalance. We need to take estrogen out of that equation—by meeting our estrogen needs fully—before we are looking at any chance of making a reasonable assessment of our progesterone needs.

So do I ever need it?

Maybe yes; maybe no. It's easy to read online and come across the assertion that because we used to make it with our ovaries and now don't have ovaries, of course we need to take some as part of our hrt. But as with many such simplistic assumptions, that isn't the whole story and is likely to lead us astray if we just take it at face value.

Yes, if we had an oophorectomy we did lose our ovaries and that reduced production. But at the same time, anyone in the menopausal lifestage has lower hormone needs overall because they're not supporting fertility, the consumer of most of our (former) ovarian output. The way it works out, then, is that our adrenal production capability typically matches our post-fertile needs just fine. It's not that we're not using progesterone; it's just that we often don't need to supplement beyond what we're already producing. HRT dosing is about unmet needs, not overall systemic needs. We still produce most of what we need ourselves; we only need hrt to close the gap between what we make and what we need for post-fertile physical functioning.

Many of our bodies actually do just fine meeting progesterone needs once estrogen needs are met fully. Many of us in surgical menopause, if we decide that we need to supplement progesterone, need do so only at a very low level, well below the typical prescribing levels based on the need of those with uteruses.

How do we decide, then, whether or not we need to supplement our post-ovarian progesterone supply? Once our estrogen needs are fully met and we've had a month or two to settle in on that adequate supply, we can look at remaining outstanding symptoms. We've discussed balancing progesterone and the symptoms of progesterone imbalance elsewhere on this site, and that's where you should go for the details on that part of the process.

If we are in fact experiencing effects that are indicative of low progesterone coverage, then we might experiment with a small amount of progesterone to see if that makes the difference we hope.

Remember: our goal in surgical menopause is to meet our current, post-fertile needs, not the needs we may speculate we had in earlier life stages. Excessive progesterone supplementation leads to very unpleasant symptoms as well as some very significant risks. It's also not magic: it only "fixes" things that are directly attributable to a deficiency of its actions. Further, because progesterone interacts with many hormones and many systems, the process of altering our progesterone levels is the most uncomfortable of all our ovarian hormone adjustments. Working with a small trial dose to see what effect that has before jumping in with both feet is far more gentle on our bodies than over-estimating and then suffering the disruptions of a large transition and a situation of excess.

Therapeutic use or disuse of progestogens

We don't want to leave this topic without taking note of a few special situations. Some of us don't have the luxury of adjusting our hrts solely for optimal balance and wellbeing, and many of those situations involve progesterone.

Individuals who have endometriosis often use a progestogen to help suppress the growth of their endo implants. For that strategy to be effective, they need to deliberately produce a situation of progestogen-heavy imbalance to be sure all of the influence of the estrogen they are taking is countered. For them, the needs of endo control take a higher priority than just comfort although there are some measures they can take to reduce that systemic impact and risk (which is covered in that link just above).

So too, individuals who have no ovaries but still have their uterus will need a progestogen to prevent the estrogen they're making and taking from causing a cancerous stimulation of their uterine lining. This is another situation where health needs trump comfort, although there are methods of managing those progestogens to limit their influence in overall hormone (im)balance (which is covered in that link just above).

Some, however, will want to exert special care when working with progestogens. Those of us with Polycystic Ovary Syndrome (PCOS) often have elevated testosterone levels, even once their ovaries have been removed, and for them, the fact that progesterone can be converted to testosterone often raises their risk situation more than reaching for better hormone balance might improve it. While the hormonal perturbations of PCOS are not yet well understood, in practical terms, supplementation of progesterone by these individuals rarely seems useful or productive of improved hormone comfort.

Those with metabolic diseases such as diabetes or PCOS may also need to watch their progesterone very closely for another reason: progesterone tends to worsen insulin resistance when it is heavy in overall balance related to estrogen. While good hormone balance has a normalizing influence upon our metabolism, we need to use extra care to be very slow and gentle when making adjustments if we need to avoid upsetting our sugar/insulin dynamic.

And those with autoimmune disorders of the inflammatory sort may find that progesterone supplementation, especially when first introduced or when used to excess of needs, can worsen their disease control. There are no absolutes here, but because progesterone affects the type of inflammatory/anti-inflammatory factors our bodies might make, use of progestogens hrts can be more complicated for autoimmune sufferers.

So what's the bottom line?

We only need to supplement our progesterone when we need a larger supply than we are producing. That's something we can't even begin to determine until we're meeting our estrogen needs as well as possible. It's also important to remember that progesterone is a powerful hormone and can be just as disruptive as it can be valuable if used out of balance with our overall needs, whether for hormone balance or disease control.

And if we're discussing progesterone supplementation with our doctors, we need to be clear that we're not talking about the standard prescribing indications for progesterone, but rather a small increment of coverage that will make our estrogen hrts a better fit for us. How well we're prepared to provide such justification rather than simply asking our doctors "don't I need some progesterone too?" will have a great influence on how that conversation goes. There are many answers to the question of whether progesterone supplementation is needed, and we need to do the thinking beforehand to be sure which question it is that we are asking if we want to receive a useful and productive answer.

Can't I just have some instructions on how to do this, please?

2009-12-18T11:05:00.005-07:00

It happens all the time: a new member comes to our discussion list to say:

This is all too hard! I don't want to learn to be a doctor! Just tell me what works for you all so I can get the same thing and be rid of these symptoms that are driving me crazy.

This same question applies to searching for hormone balance once we're launched into the process:

if I have bothersome symptoms that I attribute to hormone imbalance, is there a way to go about replacing hormones knowledgably, or is it just a shot in the dark?

Sadly, there isn't just one good answer, one best hrt that will make each individual feel just the way they want to. All of our bodies are different; our lifestyles are different; our family/genetic histories are different. How any given hrt will function in any one person's body depends upon all of those little details where those differences lie. Beyond that, medical science does not yet have enough insight into how our ovarian hormones and menopause actually function in our bodies in order to predict any of this. There is no lab test that says this hrt, this is the one that will make you feel the best.

While we cannot predict how we'll respond to any hrt or hrt change, there is indeed a series of systematic steps that we can bring to the process of trying different hrts and dosages on to see which fits our own body best. It's not a firm rule by any means, but we've developed a rough decision tree that seems to work for covering the essentials.

It's also, we need to add, very very useful to journal symptoms carefully during the process, because each decision point is driven by how our bodies respond. While lab tests can tell us if we're terrifically off base, they can't tell us when we feel good or if we could feel better by making this or that adjustment. Only our bodies can do that, so we need to learn to listen very attentively and remember what we've heard, preferably by keeping good notes. If you're unclear on how to get going with a journal, we've created a rough draft spreadsheet workbook (note that there are additional pages, listed across the bottom, beyond the one that opens). Feel free to save a copy and modify it to suit your own needs, either on your computer or by printing it out. While there are no limits to the format that suits this purpose, reading through our version might help you get a better feel for what you want to be recording.

As you read through these steps, first read them straight through. Each section contains links to either supporting documents or much more detailed information on those topics that is found elsewhere on this site. When you're ready to explore a section in detail, by all means go follow those links. But for overview purposes, we've tried to keep this discussion focused on the process, not the content. Ready?

Step 1: Which hormones?

We begin our consideration of our hormone supplementation needs by deciding where we will begin: what hormones we will work with. While individuals taking therapeutic hrts to treat or help control a specific disease condition (like endometriosis or cancer risk) will often need to work with multiple hormones at once, most others may be better advised to begin with just estrogen, planning to achieve its best possible balance before adding to the complexity of the process by adding additional hormones to meet specific objectives.

We didn't just make this up (and we offer this knowing full well that many sales pitches will tell you just the opposite). This is the basic premise of the medical specialist statement, American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause (free signup required to read). They are, if you are unfamiliar with the term "endocrinologist," the specialists in dealing with hormones. We find their reasoning compelling: because other hormones can be converted to estrogen if that hormone is deficient in supply, we really can't get a picture of other hormone needs until that estrogen need is satisfied. Until that time—and this is a critically important concept—we're just using those other hormones to prop up a suboptimal estrogen situation. Only when our estrogen needs are well met can other hormones fall back into their own roles such that we tell whether or not their supply is adequate.

Step 2: What type of hormones?

A useful way of categorizing hrts is by type: synthetic or human-identical. If you're not sure what "human-identical" means, we are increasingly switching to the use of this term because compounding pharmacists have taken over "bioidentical" as a marketing term for a specific hrt-and-testing sales program, making it confusing to determine whether the word is being used in a generic or proprietary sense. In this instance, then, we're simply distinguishing between those hormones that are chemically identical in structure to our own from those that are not, once in our systems.

This, as all decisions at the top of the tree, will be in part guided by preference and in part by personal health considerations.

What would constitute such a preference or risk? Some vegetarians might eschew an hrt from animal origins. Others have ethical objections to the way some hrts are manufactured. Some individuals are tailoring their hrt to help treat or control hormone-sensitive disease states like cancer or endometriosis and may need an hrt that cannot be converted to any other substance or that has a metabolic pathway possessing certain characteristics. Yet others may see hrts as split between overly pharmaceutical and more "natural" according to chemical structure. These are all perfectly reasonable preferences to hold and your doctor should certainly be willing and able to work within them.

Do you have to decide this right away? Nope. This is just one criterion by which you can winnow the whole field down to a reasonable number of candidates. If you prefer to skip this step, fine: you'll just have a wider selection to choose between.

Step 3: Delivery by which route?

Next we'll further narrow our choices by looking at route. Each route has specific benefits and risks, and lifestyle factors will come into this decision as well.

We may make a route decision based upon therapeutic needs: someone taking thyroid hormone might opt for a non-oral hrt so that the two supplements don't conflict with each other. Some route choices may relate to health situations: a different individual with digestive issues might eschew an oral, while another with a skin disorder might not feel comfortable with transdermals other than transbuccal or vaginal. Those who work outdoors in a very hot climate might find that patch hrts will be fighting an uphill battle for adhesion. Others caring for infants may not choose to use an hrt like a gel, which remains on the skin for a prolonged period and can be transferred to others. We all have unique factors in our lives and health situations that may make one or more routes either undesirable or sound like just the right combination of convenience and plausibility.

Step 4: At last we get to the specific hrts

Having thus lopped whole chunks of the list off as being unsuitable for one reason or another, we should now have a shorter list of hrts that meet our initial criteria.

Now we can examine the specific hrts, all listed on the estrogen pages (US, UK) of the hrts section of this site. We need to review the discussion of them in these listings as well as the supplementary information, usually the prescribing information pamphlet, linked to for each one. This may further help us determine where we feel our best starting place may be.

For example, a person wanting a transdermal estrogen but concerned about transferring hormones to small children might opt for a cream, with rapid skin penetration, or a patch, which is covered by the backing, over a gel, which forms a reservoir of hormones on top of the skin and easily shared. These kinds of details are in that discussion and can have a great deal of bearing on what specific hrts within a general route-related family will best suit our preferences.

If you're getting confused and losing track of all of these various criteria and how they apply across the estrogen hrts list, we've made an Estrogen Selection Matrix for both US and UK estrogen-only hrts. Print a copy or copy/paste it into a spreadsheet program, and just start crossing out the lines with characteristics that you don't want. Eventually you'll come down to those you are ready to read more detail about (because sometimes a choice will come down to specific details not covered in the matrix).

It takes some time to go through all of these steps, but by gradually narrowing the available options in this way, we can eventually arrive at a reasonable number of choices that represent hrts that actually interest us out of the overwhelming number that the market offers. And by having thought through this process of justifying our choices to ourselves, we're well prepared to pitch exactly those reasons to our doctors in support of our argument that we want to try these particular hrts rather than whatever default he routinely gives to all of his patients or whichever one he happens to have just gotten a hot pitch on from the latest drug rep to visit his office.

Finally, don't forget to make sure that your health insurance coverage will cover the brand (or similar generic) or that you are able to pick up the cost yourself. Some basic hrts like Estrace are available so cheaply that it becomes more sensible to pay cash than to involve drug insurance deductibles and coverage. GoodRx can help if you want to research price deals.

Step 5: What dose?

Once we've made a choice of hrt, then, it's often simplest to start at the "usual starting dose" unless we have specific criteria to meet that would indicate otherwise. What would those be? Perhaps you distrust hrts or don't really believe you needs one, and so you want to to take only the barest minimum to see what happens. Perhaps you have previous experience to suggest that you respond strongly to hormonal preparations. Perhaps you're unusually large or small in body mass compared to the general population.

It's generally not a hugely successful idea to assume that our requirements will be higher than usual, especially when we come to a new hrt, just because our last one delivered ineffectively. Why? Because an hrt that didn't get into our systems well didn't really get a chance to show how it stacked up against our personal level of need. Similarly, if our previous experience was with oral contraceptive pills taken preoperatively, we need to recognize that this was a different blend of hormonal agents at a different dosing level, addressing a whole different situation and one that really doesn't predict our menopausal, post-fertile needs for estrogen.

If we do overestimate, it's harder to recognize excess than it is to identify symptoms suggestive of shortfall. Additionally, that recognition delay represents a period of enhanced risk, as well as taking a longer process to clear, than it requires to recognize deficiency and ramp dosing upward.

This may be where some women come into conflict with their doctors, because it's way more cost effective for them to hit things right on the first try (and impresses women with their doctor's abilities). That's great when it works, but when it doesn't, then a woman has to dig back out of that hole and it's not.... fun. So if we keep in mind that this is an orderly process and not a leap to the finish, it can be easier to have patience with this part and be more gentle with our bodies. "Start low and go slow" is not a particularly exciting sounding rubric, but in fact many of us have found that excitement tends not to be what we're looking for in hormone balancing and that it ends up being well worth taking the slower approach rather than unsnarling ourselves after an over-hasty miscalculation.

There's also a popular myth that anyone who is younger than the typical menopausal age of 50 will need very high doses of hrt because they must match their premenopausal levels. While they may indeed start a little bit higher than the 50-year-old just to let themselves down a little bit more gently, in fact they are no longer fertile and most of that higher level of hormones was going to support fertility and uterine needs. We've seen younger individuals start at several times the usual maximum dose on this mistaken premise and rapidly find themselves in miserable excess. There's no reason to put our bodies through this: the usual starting dose will generally support us enough not to be in dismal shape and we can more gently feel our own way from there. Really.

Step 6: Do it!

Okay, so we begin taking the usual starting dose of our chosen hrt.

Then we wait. And journal.

It takes 6-8 weeks for full adjustment to a change in hormone support to be carried out throughout our bodies, whether we are starting hrt or simply changing some aspect of the hrt we've been on. We don't need to wait that entire long time, however, to have first-pass sense of whether this is an hrt that is going to work for us or not.

Step 7: Is this hrt working for me?

In the early stages of a trial of a new hrt, the decision tree is first of all: working (delivering) or not. Symptoms that our hrt is not delivering are going to present as soon as our previous hrt (or pre-op hormone supply) is leaving our system and the new can be presumed to have entered it.

The amount of time this takes to show up varies with types of hrt. Patches are the most rapid and a switch from one patch brand to another should be virtually instantaneous unless there were a situation of hormone excess as well. Something like Premarin, that has a long buildup and elimination period, will take longer to judge, especially since the elimination period grows longer the longer this hrt is taken. And for all of us, it will generally take a us some months after surgery to stabilize on hrt and really get a sense that our preop hormone support is no longer having any effect.

The general rule of thumb we've seen in discussions of hrt is that it takes a week or sometimes two to have a sense of general delivery, but that will need to be modified somewhat for specific hrts. As a general rule, patches provide the fastest turnover; orals and daily-dosed transdermals are middling; Premarin and long-dosed forms (pellets, shots) take the longest to get out of our systems—sometimes months.

And of course the other major part of this turnover is the uptake/buildup efficacy of the new hrt. Again, patches work very quickly; daily-dosed transdermals are pretty close behind; orals, pellets and shots may take a few days longer and Premarin is somewhat beyond that into the weeks scale.

So when we look at what we've been journaling, we're looking for whether this is an hrt that's not delivering at all (big dramatic symptoms, usually) or one that's delivering and just needs some work to get into better step with our level of needs.

This time period of our first trial of a new hrt also gives us a chance to decide how well this hrt fits into our lifestyle and overall health. If the patch gives us hives under it or simply fails to adhere, ever, then dose isn't an issue: that patch isn't going to work well for us. If we're allergic to an ingredient, we're never going to have a chance to see if it is otherwise a good hrt for us. If we have wicked heartburn or nausea after taking an oral hrt, we're not likely to want to continue even if the hormone support is good. So there are quite a few factors that come into that early decision of "is this hrt working for me?"

And if the answer is: No

If the answer at that point is no, it's not working for whatever various reason (or none that we can determine and it just...isn't), then we pull out of that trial and select another candidate based upon the nature of the problem with the one we've just tried.

If it's rash under a patch but we really really like the patch otherwise, then changing brand addresses that issue and points out the next direction we might take. If we just can't stomach an oral, we might move back to route considerations and work through our options again. In other words, we need to decide where the failure point might have been and return to that level of our previous decision tree and take a different turning there. If we don't really know what went wrong, then we can reverse the tree and work back up it from the bottom, trying our next favorite that changes that level's characteristic.

While our doctors will often counsel us to wait up to two to three months, even when we find after a couple weeks that our hrt is making no appreciable difference or we're encountering insoluble problems trying to use it, many individuals' actual experience has shown that a massive negative result from a particular hrt is most unlikely to entirely reverse itself over time. Sure, there is an adjustment curve and small niggling irritations may ease away over time, but just flat-out reversing a major negative experience tends not to actually happen.

Your doctor will probably be most sympathetic and willing to change your prescription after you've waited your three months in misery, but why should you have to earn that change that way? Your hot flashes and teary meltdowns aren't keeping him awake at night. You have the right to make this call, to say "no, I'm not doing this any more; I don't like this one and I want something else." And that is the conversation in which you also have your next choice already identified with a pitch you're prepared to make in support of why you think it'll be better. Take notes with you and support them with data from your journal: specific data helps your doctor's scientific mind accept the validity of your experience rather than just brushing you off as a silly hysterical who's not accepting their changed circumstances and is doing too much reading on the internet.

And if the answer is: Yes

If the answer is yes to the question of whether or not our hrt is delivering, however, then we move into the realm of tuning that hrt for best possible support of our needs.

Most typically, the major issue with an hrt that is "delivering okay but" is dose. Here the question is whether or not we're experiencing symptoms that suggest the dose is either too high or too low to meet our needs. While it may be tempting to address this issue in a big jump, aiming at a one-stop answer, that impatience can cloud the process and ultimately prolong it, especially if we jump right past our needed dose.

Each large dose change we make induces fluctuations in our hormone levels that themselves add to symptoms we're experiencing. We need to wait for the symptoms due to the change to abate before we can judge the actual adequacy of the dose we changed to. This is a critically important element of hrt tweaking, and one many people regretfully fail to take into consideration as they make rapid, large, multiple changes in their hrt while they flail about looking for something, anything that will make them feel better RIGHT NOW.

But smaller dose changes, ones that are small enough that our body barely registers that change has occurred, allow us to minimize that disruption from fluctuation and slowly, gently home in towards that best dose. Obviously, some hrts can only be adjusted in fixed increments while others are infinitely adjustable. We have to work within the limits of the specific hrt we've chosen... but lack of adjustability may, at some point, actually cause us to set that hrt aside and look for a new one because it just cannot conveniently be adjusted to our actual dose need. At this point, we do the best we can, and this is where "best" = small = gentle.

At some point in this dose-adjustment process, even if we are trying to sneak up on our best dose level, we may overshoot and ease into symptoms of excess. The smaller the increment of excessive supply, the longer it can take to be apparent that we're taking too much. That's another good reason for patience, of course. But a sharp dose drop for a short period will let us clear a relatively small excess and we can then take our last incremental dose increase off the top and return to the next previous dose level to restabilize. In that way, we actually narrow in on our best dose by bracketing it, a concept well known to photographers who do the same thing with exposure settings.

Beyond estrogen

Okay, so we've tweaked that dose up and down, maybe auditioned a couple different brands or types of hrt for optimal fit, and found where we feel best on our estrogen hrt.

But wait, we don't actually feel as "best" as we were hoping to be.

If we've fully explored our estrogen hrts, feel we're on the best hrt and dose we can find, and still don't feel that we've gotten where we want to be, then we're ready to explore other hormones and drugs. We choose these according to which hormone specifically has the actions we're hoping to add or which drugs might cover aspects of our hrt that we are missing. And then we go through the same entire process with that hormone or drug while keeping our estrogen stable. We may end up needing to tweak our estrogen in the final stages of tweaking the new hrt to take relative balance into account, but we need to get pretty close first or we'll just be setting up a state of confusion we'll end up chasing until we're dizzy.

We're not going to go through all of the different other hrts and drugs and factors like the needed nutrients for metabolizing hrts (that make a huge difference in how we experience those hrts' effectiveness). You can explore more of these topics on this website using our Table of Contents to find more detail on these, and you are welcome to join our discussion forums to help troubleshoot this step. Basically, once someone has achieved some reasonable degree of stability by meeting their basic estrogen needs, some of the pressure is off and they can take the time to learn more, to explore more options. And the work they've done in learning to listen to their body and work through the process will provide them important tools to continue their refining work on their own.

Okay, now you try it

That's a general outline of the process. Yes, it's rather loose and a whole lot of this is left up to you. That may seem overwhelming, but you should keep in mind that you are the expert on your body; no one else can sense what works best for you. There is no formal process—your doctor will do much this same thing for you if you simply place it in his hands and wait passively. Unfortunately, if you're not participating, that means those decisions will be based upon that doctor's preferences and they may not speak to your own concerns at all.

Remember too, that every change we make, whether it's the whole move to a new hrt or just the tiniest incremental dose adjustment, can always be rolled back. If we're at a maybe okay place now and just wonder if X might make things better, we can always try X out with the knowledge that if it turns out not to be our answer, we can go back to its sort-of-okay predecessor, regroup, and reconsider further attempts. It's not as though each try erases all previous situations. Keeping this firmly in mind provides a safety net that does allow us to experiment with a little greater daring.

Want a little backup? We're there on our forums to help you cut through to the issues and look at where you might turn to make the next iteration of adjustments. We can't tell exactly what any given individual should do, but we can often as a group ask some questions that will help then make their own decision of what to adjust next.

Vaginal delivery of systemic estrogen HRT

2009-12-13T17:54:00.008-07:00

We've been following discussions of this topic for some time now in a number of locations on the internet and it's come up on our forums as well.

There is, of course, one vaginal-delivery systemic estrogen hrt on the market already, Femring. But we're also seeing some individuals report exploring the use of Estrace and its generics (micronized estradiol) vaginally for systemic support. And that raises some distinct concerns.

Vaginal micronized estradiol: will it work?

First of all, yes, absorption through vaginal tissues will function as a delivery route for this hrt. Oral mucosa is very similar to vaginal and it is indeed permeable to this molecular form of estrogen. In fact, it's been quite some years now since we first heard of using a tiny bit of the dust leftover from cutting tabs for transbuccal or oral use for local vaginal supplementation. We had some concerns initially that either the colorant or the base might prove problematic since neither are designed for the vaginal environment, but that has not been the case for those who've shared their experiences with us. We've also run this past a few doctors who have said there doesn't seem to be any obvious peril beyond the issue of making sure the dose is appropriate. So that seems to be both effective and reasonable as a means of local supplementation. But that's not the same thing as using this delivery for systemic support.

Risks: concentration in pelvic circulation

Our greatest concern with using this route for systemic vaginal dosing, however, is where that estrogen goes immediately after it is absorbed.

With transbuccal use, many users see distinct local effects according to where in their mouths the tablet is placed. Those seem primarily to do with fluid retention (such as sinus stuffiness, ear fullness or transient headache) and we have speculated that they represent higher local concentrations in the part of the circulation to which they are initially delivered, before they are well-diluted. Most of those reporting this effect have had success in switching to other locations in the mouth where this is less problematic, although the non-problematic location varies (of course it does) from individual to individual.

Looking at that same aspect in terms of vaginal delivery, then, we have a concentration of estradiol—which is the active form of estrogen—delivered to local pelvic circulation. We know from research done with vaginal progesterone that this kind of concentration in the pelvic area does happen with vaginal delivery of that hormone supplement and there is no reason at all to expect that estradiol could escape a similar distribution pattern.

Now, when that happens with progesterone, that represents a desirable situation in terms of delivering a therapeutic concentration of that hormone to pelvic organs without causing a corresponding systemic concentration—and heightened systemic effects. But with estrogen, there's no real reason that this concentration would be desirable and in many situations, we're quite concerned that it isn't. Anyone with endometriosis, for example, would hardly want higher estrogen concentrations flowing directly to their endo implants. Anyone with a risk of ovarian cancer retains that risk even when their ovaries are removed because there is a (low but present) risk that before oophorectomy, micro-tumors may have escaped their ovaries to later be stimulated by that higher level of estrogen in the circulation that feeds them. This is recognized in the specific warnings for current vaginal systemic hrt, that caution high risk users about precisely this.

We know from users of the systemic vaginal ring that some find this route of supplementation to be highly uncomfortable, citing symptoms of pelvic bloating or congestion as well as stimulation of irritable bowel syndrome or bowel cramping. There is also a mixed body of evidence suggesting that higher levels of estrogen may add to incontinence. So not only do we have the progesterone model to shape our expectations but we have experience with vaginal delivery and pelvic symptoms to suggest that it most certainly does happen and we have FDA concurrence that this represents an undesirable level of risk for at least some users.

It is worth noting that Femring, the vaginally-delivered systemic hrt, uses a form of estradiol that, although human-identical, is inactive until it has been further processed in the bloodstream. This means that it is well on its way to being diluted and distributed before it becomes fully active as estrogen. It seems likely that this is deliberately done to reduce estradiol activity exposure at systemic levels to those pelvic tissues. In other words, there may be significant negative concerns with vaginal delivery of systemic estrogen that led the pharmaceutical companies to put additional funding into working around that problem rather than, more economically, just repurposing an existing product they already had on the shelf. While we may not know what led them to do so, the simple fact that they spent money on this raises the warning flag that it was probably not done without substantive reason.

Risks: estrogen activity and vaginal tissue health

Were an individual to elect to try vaginal estradiol systemic hrt notwithstanding the above risks, we would also think that a regular, detailed and careful exam of vaginal tissues by a knowledgeable practioner would be important. While the low-dose vaginal hrts are documented to have a fairly light effect on the tissues they directly contact, all that systemic-dose estrogen going through a relatively small location (even though the tab breaks up quickly, it's still not going to be distributed over a wide area of mucosa in the fairly static vagina) may have disturbing effects upon the mucosal cells in that area.

This is a concern raised by some doctors when users discuss transbuccal use, based upon similar issues seen with some sublingual and nasal drugs. Those using this route need to be careful to switch locations around frequently, visually check their oral mucosa regularly, and also ask their dentists and oral hygienists to do so as a backup. We see no reason why similar precautions with vaginal use would not be a good idea (only, of course, probably not asking your dentist to be the one do it) to make sure that we are not stimulating some sort of cellular changes that could become problematic. Remember: the reason why estrogen is carcinogenic is that it fosters growth of tumors, and that's not something we want going on out of sight in our vaginas.

Would this work with any of the oral estrones?

That's a good thought that came from our discussion of vaginal systemics on our discussion forums. We don't really know, but it seems as though since there was an Ogen vaginal cream made for local use, the oral estrones Ogen or Ortho-Est would seem to be usable transbuccally or vaginally since they contain the same compounds.

That said, many of the same concerns with respect to vaginal systemic dosing would still apply. Although estrone is an inactive form of estrogen, the conversion of estrone to estradiol occurs in cells throughout the body. A higher-than-normal local concentration of estrone might well still result in higher-than-desirable estradiol exposure to vaginal and pelvic tissues. We certainly don't see any reason why switching out estrone for estradiol would moderate risk adequately that those with specific risk factors such as endo or ovarian cancer could be confident that this would safer for them, however much the systemic impact might be gentler than all-estradiol dosing.

So should we use oral hrts vaginally or not?

We have really mixed feelings about this whole premise. That it would work to deliver estrogen to our systems, there is little doubt. It is likely that in reaching the circulation through pelvic rather than head/upper body dilution, the specific local effects that are problematic for some women with transbuccal use might be avoided.

We can't, however, see that it in any way alters the way the dose is processed by the body other than that initial concentrated absorption uptick, so the premise that it somehow is delivered more evenly than transbuccal is likely a subjective impression that is not supported by physiology. It may be different from other transdermal (general body skin) deliveries, just as transbuccal is, because it represents a different uptake dynamic and the skin/fat reservoir and transmission effects are taken out of the mix. Like the transdermals, however, it also represents a risk of transfer to a partner than is unquantifed but certainly real.

We've taken up elsewhere the issues of whether not estradiol needs to be dosed multiple times per day and whether "even" is ever a state that can be achieved (spoiler: no, it's a myth), so we won't reference those concerns here other than to say that there is nothing in pelvic delivery that would lead us to feel they are not applicable here as well. Anyone whose body is not capable of using a daily dose via this route, as with any other, is not utilizing that particular hrt well. Whether or not other hrts would better suit them is the issue here, not just the route and timing; multiple-dose dosing is a stopgap measure to try to force a fit with a deficient hrt, not a good or sustainable strategy in itself (although it's true that in some instances where trying other things is truly not feasible, stopgaps may be the best thing we have within our reach). The ability to divide a vaginal dose into micro-doses given at extremely short intervals is thus not a compelling argument that in any way offsets the risks, let alone makes this route somehow unique.

So the bottom line on this is that there's just no reason to be really comfortable with the risks that this concentration provides in this location. That doesn't mean it mightn't be the more practical option for some women, but it would require special precautions that make it nothing to be taken lightly. One of the dangers of discussion forums that focus on support rather than information is that women can advocate for use of a particular hrt strategy without any corresponding exploration—or even awareness—of the risks it poses.

We do think this notional hrt use is worthy of exploration, but that exploration should be done knowledgeably and with great care to monitor for negative outcomes. Given the widespread lack of understanding of hrt and hormone effects, though, we're afraid that users will be injured by and later regret decisions made without fully understanding those risks. Individuals with hormonal concerns may distrust their doctors because that relationship is so formulaic, paternalistic, and illness-based, ill-suiting their menopausal health needs. Yet when they engage in risks without that backup of medically sophisticated knowledge, they've lost an important safety net. Maybe it looks as though we're being too conservative in this case, but with things we can't get back from without great cost, yeah, conservative does have positive benefits.

But then what about compounded hrt to be used this way?

Are compounded vaginal estrogen hrts being prepared for systemic use? What are compounders doing about these issues? We're not seeing direct-to-consumer advertising of this type of hrt, so we don't really know if this market niche currently exists and we haven't yet encountered anyone who does.

Because there is no substantive difference between retail human-identical and compounded bioidentical hrts in terms of this risk situation, our concerns would definitely extend to those hrts as well. While doctors in theory vet the prescriptions suggested by compounders, in practice many of them tend to just pass them on as suggested by a fully qualified professional and happily pocket their share of the business income so generated. So there's a questionable safety net right there.

In fact, if they are doing so, this would be exactly where we tend to think that the FDA has a reasonable ground to be critical of compounding. This would be a major departure from what is known and tested and generalizable from other tested and licensed retail hrts. This is where their current practice model might indeed overstep their training and licensure and, of course, constitute the legal vulnerability that is being exploited by the pharmaceutical companies in response to what is actually a perceived marketing threat rather than the nominal concern for patient safety in which it is couched.

So we're going to hand this part of the question back to you. What do compounding pharmacists you are working with have to say about direct systemic vaginal estradiol hrts? And estrone used that way? Are they making and selling it? What precautionary screenings are they doing or what counseling are they doing on risks specific to this delivery? We'd be very interested to know what the compounders' take on this is. If you have any information, please do share the results of your inquiry with us.

This is an idea we need to explore just because there are indeed individuals out there claiming to be using this route and promoting it on discussion forums. The more concrete the information we have, the more useful it becomes to us, whether it's to give us the go-ahead to experiment more freely or to convince us that it's really not such a good idea after all. We're not at all opposed to exploring and pushing the envelope in search of alternative ways to use the available hrts, but we're always going to be taking a firm hard look at the risks along the way.