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
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.
