The redemption of HRT

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.

Bioidentical HRTs

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.

Primary Prevention of Cardiovascular Disease With HRT

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 must-reads

We're delighted you've found your way here to learn more about surgical menopause, but we don't want to be the only source you're reading. It's important, when we are advocating for ourselves and the way we want to define our needs, to be aware of what the medical community is thinking and what the scientific evidence shows. Those two don't always come together in our own health care providers, however, so we also need to be able to support our preferences with sound information we can share with our caregivers to bolster our requests.

We have a whole huge body of information in our bookmarks account, all tagged by the various topics they discuss. We have the most recent additions listed in our sidebar here, but you're always encouraged to browse the full collection to expand your understanding of those topics that seem most pertinent to your own situation.

When you do, you may find (sadly, this service doesn't allow us to publicly list all of our tags) that one tag in the list is simply "absolutely read this." That's because these particular articles provide an overview we feel especially comprehensive or critical to spelling out the situation we're working with. And we'd like to take a few moments to tell you about these valuable resources.

Individualizing Hormone Therapy for the Surgically Menopausal Woman

Individualizing Hormone Therapy for the Surgically Menopausal Woman (free signup required to read) is the motherlode of information specific to surgical as opposed to natural menopause. It's a bit dated now, published in 2004, but we're not aware of anything newer that contradicts the information it contains. In fact, more recent research has only provided more support for its points.

The article talks about how those entering surgical menopause will have a much rougher transition (ie—more severe and more numerous symptoms) if they are not supported by hrt immediately following surgery. This is an important point because it counters the assertion of many surgeons who are opposed to hrt use and instead feel that we should "wait and see" whether we need hrt. The article says that most of those who have an oophorectomy as part of their surgery will in fact require hormone supplementation and there are good reasons, both in terms of comfort and health, for working from that assumption.

The article also makes a very useful analysis of the WHI Study results, specifically as they apply to breast cancer and the use of estrogen alone as hrt. While huge numbers of hrt users—even those in surgical menopause—were forced to quit hrt due to the study's finding of increased breast cancer incidence with combined hrt, those results were not applicable to those without ovaries who were using just estrogen by itself. In that arm of the study, breast cancer was actually reduced by 23%, something that received, oh, about zero press in the panic frenzy. The article also notes how newer information about transdermal hrt delivery also raises the likelihood that findings of greater incidence of stroke and other forms of cardiovascular disease with hrt initiation may be controlled by route.

The other useful aspect of this article is that the authors are well aware of recent research speaking to increased mortality in those who have their ovaries removed and fail to supplement their hormones. Where much of the literature of natural menopause defines the issue as "just a few hot flashes," this article is very clear on the more significant aspects of the surgical variety.

Guidelines from the American Association of Clinical Endocrinologists

The American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause (free signup required to read) is not only an excellent overview, but it carries the weight of being a major medical consensus document coming from the specialty group that actually is most versed in all things hormonal. While it covers primarily natural menopause, it does give several mentions to the surgical version.

This is a long article, but there's not a lot of wasted space because they cover a lot of information. They look at the reasons for using hrt and they look at alternative drugs for managing specific symptoms, all within the context of research-demonstrated efficacy.

One of the things we think is most important here is that they specifically cite the priority the body places on estrogen and the importance of meeting estrogen needs before even assessing whether other hormones require supplementation.

Further, they note that many of the indications for supplementing testosterone are exactly those of a need for estrogen, making it especially important to be certain that a raised estrogen dose will not alleviate the specific problems before moving on to add other hormones. While they by no means condemn the supplementation of testosterone, they strongly urge being quite certain that the need is actually for testosterone and not estrogen, especially given the significant cardiovascular risk potential with testosterone. If you're thinking about the need for testosterone, this is a priority read.

Guidelines from the North American Menopause Society

The NAMS menopause guidelines statements for 2012 and 2017 (links are to pdf files) represent another broad consensus document from a specialty medical group. Why is consensus important? Because these documents contain the things that, in a highly arguable field, a wide range of professionals within the specialty do agree on. These kinds of documents are thus the baselines from which interpretations in clinical practice arise.

These represent an updated viewpoint, some years post-WHI Study, that debunks many of the anti-hrt myths that arose from the panic press the study cancellation generated. It also spells out very clearly the who, how long, and why of hrt use.

One of the noteworthy topics covered is the whole issue of "bioidentical" hrts. They note the confusion generated by the same term being employed for human-identical retail hormone preparations and the special marketing program of compounding pharmacists. It is remarkably level-headed in the whole disagreement regarding whether or not compounding should be outlawed, noting that the unrealistic marketing promises of some compounders are at the root of the FDA concerns while still acknowledging the value of compounded hrts for some individuals.

Finally, it's of some importance that the most recent one of these was issued in 2017. The fact that understanding and guidance in this area has not been revised since 2017 suggests that there is nothing new that substantially challenges either that understanding or the guidance built upon it. While a lot of fine detail on hormone physiology is still being filled in, primarily in the field of cancer research, the fact that the broad details are now well-established can give us confidence that we're operating from a solid scientific basis.

Guidelines from the International Menopause Society

The International Menopause Society provides updated recommendations on a variety of menopause-related topics from menopause specialists, but this time international in makeup. This was formerly one of the most conservative bodies in terms of being anti-hrt, but this revision is a lot more reasonable and less terrifying—something we obviously consider a good move.

There aren't any ground-breaking elements in these reports, including their Global Consensus Statement on Menopausal Hormone Therapy (link is to English version but other languages are offered on the website), but the overall conclusion that "benefits are more likely to outweigh risks for symptomatic women before the age of 60 years or within 10 years after menopause" is an important examination of the risk/benefit profile of HRT use.

Oophorectomy and mortality risk

One of the big shockers that turned around medical thinking about oophorectomy and hrt in surgical menopause over 20th century understanding is the documentation that removing a young individual's ovaries and not supplementing their hormones results in a substantial increased risk of dying from any of a number of causes when they is compared to someone who did take hrt. This is in marked contrast to the previous guiding philosophy, which was that hormones had no use in a non-fertile body and that the menopausal would be just as well off without both ovaries and hormones. While this risk was known for many years to specialists, more recent publicity is starting to reach out to physicians in general and become the practice standard.

Prophylactic Oophorectomy in Young Women Carries Increased Mortality Risk (free signup required to read) goes into that discovery, with the notable quote here being

Women younger than 45 years who undergo prophylactic bilateral oophorectomy and do not receive adequate estrogen replacement therapy have a 70% higher mortality risk

There is also a report on this research in Science Daily, "Preventive Ovary Removal Linked To Early Death In Younger Women, Mayo Clinic Discovers."

There are a number of other resources on this topic in our bookmarks account tagged with "oophorectomy." While many of them deal with younger individuals, the growing body of medical opinion is that this is simply a graphic example of something that affects all of us to varying degrees, no matter what our age. In other words, we need a certain post-fertile level of hormones to enable normal physical function, and when those are not provided, very significantly increased mortality risk can result.

While we have long advocated that a everyone's decision to supplement their hormones or not is a personal decision, we feel that all of us need to know that the risks are very much not on just one side of the issue. Even where there are risks on the side of taking hrt, they need to be realistically balanced against the risks of not taking hrt, lest we doom ourselves to worse outcomes than the ones we feared.

And those are our surgical menopause "must reads" for helping to gain a broader understanding of not only the physiology involved in hrt use, but the recommendations and the background behind them. If we are to effectively advocate for our preferences, it is from materials like this that we most convincingly work. It's not all easy reading, but aren't we worth the effort?

NEWS: 2007 guidelines from the International Menopause Society

This was exciting news at the time these came out, and since the recommendations have changed very little since then, we can hold onto them as providing a fairly durable understanding of best practices from the medical standpoint.

The document is the International Menopause Society (2007) revised "treatment" recommendations for menopause (free, pdf). 

In the post-WHI terror years, this major medical practice group promulgated some of the most restrictive and negative of the major sets of guidelines, providing frightened physicians the backup they needed to withhold HRT from many desperately miserable women.

But with additional analysis of WHI data plus results accumulating from other studies, a more rational outlook prevailed that goes back to a sensible, individualized approach. We really urge you to download and read this whole document, but the guiding principles section, which we are quoting, is excellent in terms of summarizing much of what we work with and believe here:

Hormone therapy should be part of an overall strategy including lifestyle recommendations regarding diet, exercise, smoking and alcohol for maintaining the health of postmenopausal women. HT must be individualized and tailored according to symptoms and the need for prevention, as well as personal and family history, results of relevant investigations, the woman's preferences and expectations. The risks and benefits of HT differ for women around the time of menopause compared to those for older women. 

HT includes a wide range of hormonal products and routes of administration, with potentially different risks and benefits. Thus, the term `class effect' is confusing and inappropriate. 

Women experiencing a spontaneous or iatrogenic menopause before the age of 45 years and particularly before 40 are at higher risk for cardiovascular disease and osteoporosis. They will benefit from hormone replacement, which should be given at least until the normal age of menopause. 

Counselling should convey the benefits and risks of HT in simple terms, e.g. absolute numbers rather than as percentage changes from baseline expressed as a relative risk. This allows a woman and her physician to make a well-informed decision about HT. 

HT should not be recommended without a clear indication for its use. 

Women taking HT should have at least an annual consultation to include a physical examination, update of medical history, relevant laboratory and imaging investigations and a discussion on lifestyle. 

There are no reasons to place mandatory limitations on the length of treatment.
Whether or not to continue therapy should be decided at the discretion of the well-informed hormone user and her health professional, dependent upon the specific goals and an objective estimation of benefits and risks. 

Dosage should be titrated to the lowest effective dose. Lower doses of HT than have been used routinely can maintain quality of life in a large proportion of users. Long-term data on lower doses regarding fracture risk and cardiovascular implications are still lacking. 

In general, progestogen should be added to systemic estrogen for all women with a uterus to prevent endometrial hyperplasia and cancer. However, natural progesterone and some progestogens have specific beneficial effects that could justify their use besides the expected actions on do not require progestogen co-medication. Direct delivery of progestogen to the endometrial cavity from the vagina or by an intrauterine system is logical and may minimize systemic effects. 

Androgen replacement should be reserved for women with clinical signs and symptoms of androgen insufficiency. In women with bilateral oophorectomy or adrenal failure, androgen replacement has significant beneficial effects, in particular on health-related quality of life and sexual function.

So, there you are in one fell swoop: no arbitrary end limit, individualization and lifestyle as important, need for HRT by younger women, goal-driven use, progesterone uses beyond the uterus, vaginal estrogen support, androgen use supported and defined—the whole thing. This is, to put it simply, very very useful.

Every one of you who has been stymied in the things you've asked for can print this out and take it to your doctor and suggest that perhaps he might find it useful to review the latest guidelines from this very conservative group. In fact, go whole-hog and take along the Endocrinologists' Society guidelines too! These two remarkable documents do more to provide us with unassailable foundations for meeting our needs than any of us would have dared hope just a few years ago.

The recommendations provide a very good discussion of risks and benefits. In particular, the discussion of breast cancer risk is very concrete and clearly points out the soft spots in many of the "scare" studies, such as the fact that the majority of the WHI participants were obese as well as over age 63—things that are independent risk factors for many of the negative effects attributed to HRTs in the initial analyses. It is also very specific about how (and by which estrogens and progestogens) breast cancer is stimulated.
For those here worried about being "late starters," the recommendations point, as we have in our discussions, to the lowered CV risk posed by transdermals and low doses.

There is acknowledgment that some drug regimens may help with hot flashes, but that additional work on risks is needed in order to compare those drugs to HRTs in terms of overall risk. This is very important for those whose doctors are frightened of HRT risks but assert that drug risks are trivial—something we have viewed with skepticism all along.

On the topic of compounded blends, the initial look is negative:

There are no medical or scientific reasons to recommend unregistered `bioidentical hormones'. The measurement of hormone levels in the saliva is not clinically useful. These `customized' hormonal preparations have not been tested in studies and their purity and risks are unknown.

But in fact this is, aside from the saliva testing disregard (which we're afraid we have to agree with for reasons posted elsewhere in some detail), this is actually a dazzlingly neutral stance considering the strong anti-compounding lobbying the pharmaceutical manufacturers are carrying out in conjunction with the medical insurance companies. Failure to condemn them holds the door open to possible future endorsement once ("if" is actually the more likely situation, considering the funding of research being primarily provided by pharmaceutical companies) more targeted research is performed. This is, again, more positive than we might have expected from this group and the overtly political process that forging such a public statement involves.

The rest of the document is a set of bullet points on specific symptoms, systems, and recommendations. These are all in really quite readable text with a minimum of medical terminology. The osteoporosis section, for example, recommends 700 IU of vitamin D daily in addition to calcium. That's an encouragingly updated figure from an authoritative and conservative source, for those looking to feel supported in moving their dose up beyond the old US FDA standard of 400 IU.

Basically, this ticks through every system and records, clearly, the findings of research and how they pertain to practice. It is very clear on the benefits of HRTs and how to minimize the risks (repeated emphasis, for example, on where transdermals differ from orals).

Oh, and we can't resist quoting this, for those of you whose doctors have insisted that you are just crazy when you complain of brain fog and memory loss:

New results from recent in vivo randomized, controlled neuroimaging experiments demonstrate that, in young females and those in midlife:

•  brain function is modulated by normal variation in ovarian function;
•  acute loss of ovarian hormones increases neuronal membrane breakdown;
•  acute suppression of ovarian function is associated with reduced activation of brain regions critical to memory.

So go, download and read this through. If you want the current state of the art thinking on hormones and HRTs, this is pretty much it.