Estrogen treatment

Midlife Muddle - Own the Power of Naming

Bonnie — Fri, 25 May 2012 11:01:32 -0500

This article originally appeared as post on the Society for Menstrual Cycle Research re:Cycling blog.

By "midlife muddle" I don't mean the trouble concentrating or remembering names that sometimes occurs for all of us (but more frequently if we've wakened with night sweats and not gotten back to sleep). I mean the condoned and official confusion about naming of women's reproductive aging. Let me show you why I am upset.

STRAW+10 staging system for reproductive aging in women
Stages of Reproductive Aging Workshop (STRAW) held a 10-year anniversary last summer. (As someone frustrated by not being "heard" at the original conference, I still think that the "W" in STRAW should stand for Women!) Despite that, STRAW+10 has made progress because at least some of the classification is now supported by population-based prospective data rather than based on what experts believe. The names that are now politically correct are summarized in the STRAW+10 Executive Summary¹ and the diagram¹ at right.

We in the Society for Menstrual Cycle Research have also had our say about nomenclature: "Naming Women's Midlife Reproductive Transition". I wrote this (with revision and refinement by collective effort of SMCR members) because women keep getting left out of this naming business. For example:

•a regularly menstruating woman with night sweats, heavy flow, and increased cramps could learn to call herself perimenopausal² (not STRAW+10 Late Reproductive Phase -3b?!).
•a woman who just finished her period can say, I'm in late perimenopause and have at least a year without further flow before I'll be menopausal. Based on STRAW+10 she could be told that specific menstruation was her final menstrual period (nickname "FMP") and the next day, according to STRAW+10 be told that she is now "postmenopausal"!!
•a woman with sore breasts, irregular periods, and heavy flow could say, I'm in perimenopause. However, she may instead be told she is in the "Early Menopausal Transition." Because she has heavy flow she is also likely to be prescribed the birth control pill (as is currently and commonly recommended). Usually she will not be told that The Pill will make her perimenopausal irregular flow worse-she may well start spotting in the middle of her cycle.³
This new and improved STRAW+10 still centers all of women's reproduction on that mythical FMP. But to call the FMP "menopause", as many women's health experts do, is just unscientific. It takes at least a year without another menstruation in those of us over age 45 before nine out of ten of us will not get another period4. But one (out of ten) of us will get a further, normal period even though we've been that whole year without any⁴. We can tell that new flow is normal (in other words, does not need investigation for endometrial cancer) if we had cramps or bloating or sore breasts or moodiness-or all of these-that told us our period was coming.

So our new Naming position statement says don't call it "menopause" until you've not had a period for a year. And do call it "perimenopause" if things are variable and changing even if you are still having regular flow².
Three of nine changes can confirm for you that you are perimenopausal even if your flow is still regular:²

1.Shorter cycles (25 days or less);
2.Increased cramps;
3.Heavier flow;
4.Increased trouble sleeping-especially waking up in the middle of sleep;
5.New or increased migraine headaches;
6.Night sweats-especially if they tend to occur before or during flow;
7.An increase in or new premenstrual mood swings;
8.New sore, enlarging or nodular breasts; and
9.Weight gain without changes in what you eat or the exercise you do.

If women can learn to call themselves perimenopausal, they will be saying they know that perimenopause is not the same as menopause-perimenopause is a midlife transition with higher and erratic estrogen levels. Menopause is a fairly stable life phase with normally low estrogen and progesterone levels that begins one year after their last menstrual flow.

Furthermore, by naming themselves accurately they will be able to tell whether a medication that is proposed for them has been tested and proven effective in perimenopausal women. Usually symptomatic women are treated with oral contraceptives (that are proven reasonably safe and useful for premenopausal contraception), or offered hormone therapy that has only been tested and shown effective for hot flushes/flashes in menopausal women.

So. . . I like the word perimenopause and think if women understand and own it they will be on their way out of a midlife muddle.

References

1.Harlow, S. Executive Summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging [pdf]. Fertility Sterility, 2012 doi: 10.1016/j.fertnstert.20012.01.128

2.Prior JC. Clearing confusion about perimenopause. BC Med J 2005; 47(10):534-538.

3.Casper RF, Dodin S, Reid RL, Study Investigators. The effect of 20 ug ethinyl estradiol/1 mg norethindrone acetate (MinestrinTM), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women. Menopause 1997; 4:139-147.

4.Wallace RB, Sherman BM, Bean JA, Treloar AE, Schlabaugh L. Probability of menopause with increasing duration of amenorrhea in middle-aged women. Am J Obstet Gynecol 1979; 135(8):1021-1024.

What should I expect after early surgical menopause?

Elyse — Tue, 25 May 2010 12:40:23 -0500

Now Available! The Estrogen Errors: Why Progesterone Is Better for Women's Health

Elyse — Tue, 17 Feb 2009 13:31:28 -0600

In this revealing work, Dr. Jerilynn Prior teams up with Susan Baxter, a medical writer, to explain the controversy over medicine prescribing estrogen for perimenopausal women in the United States, and to detail why progesterone is actually a far more effective, and a far less risk-ridden, approach. Citing long-standing and emerging research, patient vignettes, and personal experience, endocrinologist Jerilynn Prior and writer Susan Baxter tell us how false beliefs on estrogen became entrenched in U.S. medicine and culture, and why business and politics have played a role in this erroneous thinking.

Like most women in Europe, Prior's patients find progesterone the key to dealing with a life cycle transition that, contrary to Western medicine, these authors do not see as a disease. Challenging medical orthodoxy, this work presents arguments and evidence both women and doctors will find compelling and useful.

Author Information

Susan Baxter is a medical writer and social scientist with more than 20 years experience writing on controversial medical topics. She teaches part-time at Simon Fraser University. Her articles have appeared in publications including Family Practice, Medical Post, HealthWatch, Lifeline, and Easy Living.

Jerilynn C. Prior, MD is Professor of Medicine, Division of Endocrinology, at the University of British Columbia. She is Founder and Scientific Director of the Centre for Menstrual Cycle and Ovulation Research, and has authored research published in journals including The New England Journal of Medicine and the Journal of the American Medical Association. Prior is a Diplomate of the American Board of Internal Medicine, and a Fellow of the Royal College of Physicians and Surgeons, of Canada. As a clinician and researcher, she has treated thousands of women. Prior has been Visiting Lecturer across Canada and the United States at schools including the New York Academy of Sciences, Harvard School of Public Health, and Albert Einstein Medical School. In 1985, Prior won a Nobel Peace Prize for her work with Physicians for the Prevention of Nuclear War.

What others are saying about The Estrogen Errors

"Jerilynn Prior can always be trusted to go beyond the surface to what is really happening in women's bodies. She is a true champion in women's health. This book will help you finally understand your body and hormones."

-Susan Love MD
President of the Dr Susan Love Research Foundation and author of Dr Susan Love's Breast Book

“In this provocative book, Jerilynn Prior and Susan Baxter raise many key questions that women's health researchers and clinicians have failed to ask or investigate. They are especially effective in deconstructing prevailing myths about "too little estrogen" during the peri-menopause.”

-Judy Norsigian
Executive Director, Our Bodies Ourselves

"Estrogen Errors" is, quite simply, the truth! Jerilynn Prior has done women a huge service by uncovering the real truth about estrogen and the hidden secrets of progesterone! A must read for anyone concerned about women's health."

-Christiane Northrup MD
Author of The Secret Pleasures of Menopause, The Wisdom of Menopause, Women's Bodies, Women's Wisdom, and Mother-Daughter Wisdom.

"Estrogen Errors tells the story of efforts to set the record straight about how healthy ovulatory menstruation - with its ebb and flow of estrogen and progesterone - protects our hearts, breasts and bones and details with sound scientific evidence the implications of this knowledge for women's health. It is also a call to action for women to become body literate. We owe it to ourselves and our daughters to understand and appreciate our bodies if we want to make conscious, informed decisions about our health throughout our reproductive lives - from menarche through to menopause and beyond..."

-Laura Wershler
Executive Director, Sexual Health Access Alberta

Estrogen Errors is now available in hardcover and as an e-book!

You can order your copy at your favourite online retailer, including:

Amazon.com

Amazon.ca

Barnes and Noble.com

Or visit your local bookseller and request a copy using the following ISBN number:

ISBN 0-313-35398-0 or ISBN 978-0-313-35398-7

A portion of all proceeds from the sale of The Estrogen Errors will be donated to the CeMCOR Endowment Fund to ensure that the research and outreach intiatives of the Centre for Menstrual Cycle and Ovulation Research continue well into the future.

Estrogen Errors has its own web page and blog

Follow us online at EstrogenErrors.com

Bewildered by Bio-Identical Hormones

Elyse — Fri, 13 Feb 2009 18:35:26 -0600

Blood Clots and the Birth Control Patch

Elyse — Mon, 08 Dec 2008 12:20:54 -0600

WHI, One Year Later — WHY?

Elyse — Fri, 09 Nov 2007 15:38:31 -0600

It has been a year since the Women’s Health Initiative Estrogen plus Progestin (WHI) arm of this large trial was stopped early because it caused harm (1). But people are still talking about Hormone Replacement Therapy and estrogen deficiency. Why?

Little has changed because the fundamental, negative ideas about women and about menopause have not changed. Universal menopausal hormone therapy and condemnation to disease and deficiency after menopause are based on a cultural belief that women are inferior and need fixing. The purpose of this article is to outline the prejudice against women on which these concepts of “estrogen deficiency” and “replacement” are based, to identify the ways these ideas are unscientific and to propose some things we can do to change these harmful ideas.

First, a personal word. I am a specialist physician for whom studying, practicing, teaching and creating new science about women’s reproduction is my life work. For over twenty years I have been saying that menopause is a natural part of women’s life cycle, the low estrogen levels after menopause are healthy and not abnormal. This made me unpopular—I have been labeled me as “way-out” or worse. Therefore the WHI results for me were a vindication.

The apparently positive responses of menopausal women to estrogen therapy were the keystone in the arch of reproduction-based prejudice against women. With WHI’s destruction of that keystone, the arch should fall. Right? Not right because the strong cultural negative ideas about women remain. For me, the Women’s Health Initiative estrogen plus progestin trial results provide evidence-based proof of misogyny.

What do I mean by that statement? Let’s start with the tough one—the word “misogyny” is harsh. In Norwegian it roughly translates to “woman hating.” Misogyny means that unintentionally or intentionally women are being treated badly—this is commonly supported by a negative view of women’s contribution to the society and different reproductive biology compared with men. However, women are normally different. Women’s estrogen levels in our normal life cycle do decrease to low after menopause. By contrast, men’s testosterone levels, although they decline somewhat in older ages, on average continue to be high throughout a man’s lives. Thus the concept of “estrogen deficiency” arises. And from that follows the prescription of estrogen to all menopausal women to prevent the supposed negative effects of low estrogen levels. But, as Dr. Susan Love said, “If estrogen deficiency is a disease, all men have it!” (2).

The strongest evidence for the belief that menopausal women are estrogen deficient has been that estrogen treatment apparently decreased heart attacks and dementia and was beneficial to women’s health and well being. In the early 1990s being filmed for “The Best Years” for the Canadian Broadcasting Corporation, I was asked by Joyce Resin to respond to Dr. M. Gelfand’s statement that estrogen improved women’s quality of life. My immediate response, “Better quality of life with estrogen is a smoke-screen for keeping women diseased and dependent.” (I realized how radical that sounded as I was saying it! I unconsciously ended the sentence with a slight questioning upturn in my voice.) WHI results show that estrogen does not improve the quality of life for women (3).

The Women’s Health Initiative, the largest controlled trial of ovarian hormone therapy ever performed, provides the strongest proof that Medicine (which is part of Culture and has been strongly influenced by the Pharmaceutical Industry) causes harm for women. Further a meta-analysis of controlled trials shows the same thing (4). This requires that the concept that “menopause-means-estrogen-deficiency-needs-replacement” must be replaced with a scientifically accurate and non-prejudicial idea about menopause.

To explain further—WHI estrogen plus progestin results are “evidence-based.” What does that mean? Modern medicine, to ensure scientific support for health care decisions and therapies, demands that what I, as a physician do, be based on good evidence, ideally from randomized controlled trials. It requires that I test my ideas (for example, about the use of cyclic progesterone for heavy periods or progesterone daily for treatment of hot flushes) in randomized controlled trials. It also demands that I abandon any therapy ideas that haven’t been proven both effective and safe in controlled studies. As a 23-year veteran of research in women’s health, I heartily agree with the goals of evidence-based medicine.

Evidence-based medicine is also founded on that fact that different kinds of studies have different value from clinical impressions, to observational studies to controlled trials to meta-analysis of controlled trials. At the bottom of the list is a doctor’s or many doctors’ impressions: “X is beneficial because my patients feel better.” That is biased because the women a given doctor treats are not representative of all women and came with a problem expecting help. It is also biased by the relatively small number of women one physician cares for (because some important harmful effects are relatively rare and therefore would not be expected to occur in the practice lifetime of one physician). And finally because in general happy patients come back and unhappy or harmed ones may disappear, or if they return be considered anxious or their side-effects discounted. The opinion of doctors has been that estrogen therapy is good for women. The company making estrogen has played a very strong role in the education of today’s physician leaders, especially in the field of gynecology. The idea of treatment with estrogen rested on the culturally accepted and fundamentally prejudicial idea that menopausal women are ill, or becoming that way, because of estrogen deficiency.

Did doctors and scientists have evidence-based data that estrogen therapy was beneficial for menopausal women? Sort of. All kinds of observational studies showed it. Observational studies enroll volunteer women who, for example, are all asked whether or not they have ever used Therapy Y. The differences in outcomes (let’s say Disease D) between those using and not using Therapy Y are all credited to or blamed on Therapy Y. But there are many unmeasured differences that may be present between groups using or not using Therapy Y. These may or may not be directly related to Therapy Y, and may or may not directly influence Disease D. Observational studies in the dozens involving hundreds and thousands of women have almost consistently shown that menopausal women taking estrogen were less likely to have heart attacks.

However, in observational studies the women who asked for estrogen, or whose doctors insisted they take it, tended to be healthier. In the United States of America estrogen-requesting women tended also to be of higher socioeconomic status and education (and would therefore have health insurance that over 35 million in the USA don’t). In real life as well as in studies, women who were prescribed estrogen were healthier (the healthy cohort bias) (5). Doctors also followed women taking hormone therapy more closely so they would have likely have had any illnesses detected and treated earlier (ascertainment bias). And women who kept taking estrogen were healthier simply because they were good pill takers—the compliance bias occurs because good takers of placebos have better health than erratic pill-takers (6). Therefore, estrogen was considered to prevent heart attacks and the consistency of the evidence from many studies was used as proof. So strong was this (biased) belief that a medical Professor, and leader in a large and reputable disease-focused organization in Canada demanded that I, as an invited speaker to a forum on Menopause and Osteoporosis in Toronto, say that estrogen prevented heart disease. When I protested that there was no randomized, controlled trial evidence for that statement, I was told I “had” to say it. I ended up saying that most physicians believed that estrogen prevented heart disease followed quickly by the statement that I thought that was not true because only lower quality, biased studies had shown it.

The strongest kind of study in evidence-based medicine is a double-blind randomized placebo-controlled trial. Double blind means no one conducting the study, participating in the study or making judgments about lab tests knows the real nature of treatment each participant is receiving. Randomized means that there is a rolling of the dice kind of assignment to different therapies. Placebo-controlled means that one of the therapies is inactive or a placebo. In the case of estrogen therapy for heart disease prevention, a randomized placebo-controlled trial in men without heart disease was prematurely discontinued in the 1970s because it showed that estrogen treatment caused heart disease as well as other serious risks in men (7). Results from that study should have demanded that a similar high-quality study be performed in women before prescribing it for heart disease prevention. Instead, those data were virtually ignored and hundreds of observational studies (remember, a less strong design) were funded, conducted and published. Meanwhile, millions of healthy menopausal women around the world, especially in North America, have been taking harmful hormone “replacement” therapy for disease prevention.

About two decades passed after that trial of estrogen in men before science-based feminist groups (such as the National Women’s Health Foundation in the USA) and the collective writings of skeptical feminists (2;8;9) had an effect. A randomized controlled trial of heart disease prevention with estrogen, the Women’s Health Initiative (WHI), was begun. Although the estrogen plus progestin arm was stopped, WHI has many other arms that are still ongoing including one testing only estrogen in women who have had a hysterectomy. That study arm, which has about 5,000 fewer women enrolled, has less statistical power to show potential negative effects on heart disease. It may also not show the breast cancer risk of the study in women without hysterectomy because women who have had a hysterectomy, even if ovaries are conserved, have lower basic risks for breast cancer (10). In addition, other ongoing arms of WHI are studying calcium and vitamin D for osteoporosis prevention and documenting whether a low fat diet compared with a conventional one prevents breast cancer.

The WHI Estrogen plus Progestin arm (E plus P) tested therapy with conjugated equine estrogen (estrogen from pregnant mare’s urine, Premarin®) plus very low dose medroxyprogesterone (a created kind of progesterone called a progestin, Provera®) both taken daily. Women enrolled did not have severe hot flushes and night sweats, heart disease, osteoporosis or breast cancer because the idea of the study was to test the popular concept that E plus P would prevent the chronic serious diseases that menopausal estrogen deficiency was supposed to cause for all women. The WHI showed the opposite of what was expected—E plus P caused heart disease and breast cancer as well as blood clots and strokes. E plus P also prevented osteoporotic fractures including hip fracture and bowel cancers but these good things did not begin to counterbalance the bad (1).

The ultimate scientific proof is present when several double-blind randomized placebo-controlled trial results are analyzed together to provide what is called a “meta-analysis.” It should rather be called a “mega” analysis because it involves thousands of participants and carries great scientific weight. A recent meta-analysis of long-term ovarian hormone therapy that includes the WHI E plus P results shows no benefit in heart disease prevention and further documents that estrogen causes stroke, blood clots and breast cancer (4).

Any logical person much less a scientist would now say that the WHI results require re-thinking of the concepts on which menopausal “replacement” and “estrogen deficiency” were based. The arch of prejudice against menopausal women should crumble. Right? If the arch itself still stands, though perhaps it has become a bit wobbly, this says something. I think it is further proof that the menopause-equals-estrogen-deficiency idea is a cultural prejudice against women. In being asked about the WHI’s discontinuation Dr. Wulf Utian, executive director of the North American Menopause Society, said, “It’s not just a matter of what the data says—truth is opinion” (11). He is counting on societal prejudice to spin WHI results and to maintain the status quo.

Another aspect of the response to the WHI that bothers me is that women were forgotten in all the hype about the study’s abrupt termination. The website for the WHI study said, “Women with a uterus should stop their study drugs immediately.” Following that order led to hot flushes in many women who were on hormone therapy. And women who heard the news of the study in the media also often stopped their therapy abruptly (12). That led to severe hot flushes in hundreds of thousands of women and in virtually all women who had previously experienced them. Because it is well known that rapid withdrawal from estrogen causes night sweats and hot flushes, all physicians should have been ready with advice for women wanting to stop estrogen. However, the few resources available are those provided by feminist physicians (www.drsusanlove.com; www.cemcor.ubc.ca ). Without helpful information, and because night sweats/hot flushes are so miserable, many women, in desperation, have reluctantly restarted unwanted estrogen treatment.

Back to evidence-based medicine. Although, both as a scientist and a woman, I strongly support evidence-based medicine the process through which our society creates science is complex. The process begins when, as a clinician, I feel a need for new therapy. Let me be specific—about 25% of midlife women have heavy vaginal bleeding (13) because of high estrogen levels and low progesterone levels during early perimenopause (14;15). A physiology-based therapy would right this hormonal imbalance by giving a high dose of natural progesterone for at least 14 days at the end of the cycle. Progesterone’s job is to counterbalance estrogen’s effects everywhere in the body but especially to cause thinning of the endometrial lining of the uterus and to decrease heavy flow.

Given this identification of an important problem for women, and after many years of successfully using this new therapy in clinical practice, colleagues and I at the Centre for Menstrual Cycle and Ovulation Research decided to apply for funds to do a controlled trial. We then spent several months working through nights and weekends writing and assembling the complex data needed for a grant application. This proposal was to test the use of high dose cyclic progesterone in a randomized double blind, placebo-controlled trial and compared with birth control pills, the standard treatment doctors currently use for heavy bleeding in midlife women. We sent this application to Canada’s publicly funded scientific granting agency, the Canadian Institutes for Health Research.

Response—this application is funded because it is important and because perimenopausal women currently make up a large portion of the population of women in Canada. It is funded because it could potentially decrease women’s anguish at flooding menstruation, women’s time lost from work, could prevent most hysterectomies and is a women-centred and physiology-based therapy. Wrong. It is three times rejected and each revision is criticized in a different way. Why? Perhaps because it is not about molecular genetics (science has its fashions) or perhaps women’s bleeding, because of society’s taboo (16) triggers a negative response in the largely men on the “peer review” committee. Or perhaps this was rejected because our outcome measure, vaginal flow, was assessed using two kinds of women’s self-report data from a standardized diary form (Daily Perimenopause Diary (17)) and was not a “hard” endpoint. Whatever the reason, it means that as a physician I am left to prescribe and teach about a therapy that is not evidence-based. And that every day hundreds of midlife women have their lives disrupted by heavy flow or undergo unnecessary surgeries.

Another part of the process of making science is that the results of a study must be published. In the realm of science, something that is unpublished doesn’t exist. I once got funding for and successfully completed a trial of cyclic medroxyprogesterone treatment for bone loss in healthy, active young women whose menstrual cycles or ovulation were disturbed. That study used a randomized, double blind design and was placebo-controlled. Further it showed the highly positive results that progestin therapy significantly increased bone density while the placebo-treated women lost bone. When I submitted the manuscript of these results it was rejected nine times over three years before it was eventually published (18). During those frustrating three years, I nearly lost my application for tenure at the University of British Columbia. This means I was almost fired from my job. The process of creating evidence-based medicine is fraught with hazard for a feminist scientist.

So, let’s get back to WHI, menopause, evidence-based medicine and prejudice. I believe that we have a unique opportunity, right now, as women at this anniversary of the initial WHI results. We must call attention to the negative ideas about women that are part of our culture and that WHI so clearly illustrates. Destroying the concept of estrogen deficiency will be hard. Don’t forget that we, as women, are also members of this culture and at least in part adopt much of what culture believes about women. It is now time to declare that menopause is a normal part of every woman’s life cycle. I call menopause “graduation.” As a menopausal woman I truly feel freed—I’ve survived the premenopausal demands of cyclic estrogen and the chaos of perimenopause which is estrogen’s storm season. As women it is now time to declare that the estrogen deficiency concept of menopause is wrong, based on prejudice and not on science.

What can we do? First change the language. I and others (19) have been trying for many years to persuade physicians, women and organizations to stop using the term “hormone replacement therapy” or “HRT.” Those terms imply that menopausal women are deficient and need fixing. Now the Federal Drug Association in the USA also says menopause treatment should be termed “hormone therapy.” (However, that term is vague and could apply to testosterone for “andropause” in men, DHEAS purchased under the counter, or ground up calf adrenal glands!) Instead “Ovarian Hormone Therapy” is a good descriptive term and rolls off the tongue in its abbreviation as “OHT.” Use it! And demand that others also say OHT.

Most thought leaders and women’s health organizations are now either directly or indirectly advocating abandoning any hormone therapy for menopausal women. But OHT continues to be an important and physiological treatment for women whose menopause came early (before age 40 or perhaps 45), for women with disturbing hot flushes especially causing chronic sleep disruptions, and for menopausal women with osteoporosis plus hot flushes (20). However, my concept of OHT is different from what many imagine. To me it means “bio-identical” or “natural” kinds of estrogen and progesterone both given in physiological doses daily unless a woman wishes flow. (If a woman desires flow I would give estrogen for days 1-25 a month and full dose progesterone days 14 through 27 of the month.) On doses of estrogen and progesterone that are equally balanced, menopausal women have no further bleeding based on my extensive clinical experience. (Note that this hasn’t been proven in a controlled trial). However, with the full dose estrogen and very low dose progestin treatment tested in the WHI, 41% of women in the hormone arm had irregular, abnormal bleeding (requiring that the randomization code be broken) as well as increased rates of hysterectomy over placebo-treated women (1). This unpredictable, abnormal bleeding, which planners knew would occur based on evidence from an earlier randomized, controlled study (21), is further evidence of medicine’s misogyny. (Would an abnormal and unpredictable penile discharge be considered a trivial complaint of a man?)

Have I changed my thoughts and practice since WHI? I have always believed that menopause is normal with naturally low estrogen and progesterone levels. And my teaching, writing and prescribing practices have always been consistent with that concept. However, I will never again prescribe estrogen as a pill. There is now overwhelming controlled trial evidence that pill forms of estrogen cause unacceptably high rates of clots and perhaps, through clotting, also increased strokes and heart disease. There are not yet strong data but it is likely that estrogen given through the skin (as a gel, crème or patch) will be less likely to activate liver clotting factors and thus safer.

In summary, the prejudicial, negative idea that menopause-means-estrogen-deficiency is the arch for which hormone “replacement” therapy was the keystone. With the negative results of the WHI the prejudice against menopause and women must stop. We now have evidence-based proof that “replacement” is harmful to women. Each of us must practice living with these important ideas—menopause is normal and low estrogen levels are natural.

What can we do? We must pressure the Canadian Institutes for Health Research to fund important research for women. CIHR must ensure that taboos and prejudice against women are eliminated from the process of allocating Canadian’s tax dollars to fund research. Until research studies rising from women’s needs are funded equitably and published fairly, the prejudice will continue. Medical journals must be pressured to review articles in a blinded fashion, without knowledge of the identity of the authors. More broadly and practically, if we hear doctors, reporters, other women, our partners, our kids or anyone saying “hormone replacement therapy,” “HRT” or “estrogen deficiency” we must hold up our hands, interrupt. “That feels to me like prejudice.” Say it strongly. “That feels like prejudice.” Further, say that these prejudicial ideas are unscientific. We have evidence-based proof from WHI. It is also time to be humble and ask why so many of us, who want to help women, previously “bought” the menopause-means-estrogen-deficiency-requires-replacement concept. Finally, although we will eventually be successful in eliminating menopause-related prejudices, all of us must be alert to the new mutations of misogyny our culture will undoubtedly create.

Reference List

Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in health postmenopausal women: principal results from the Women's Health Initiative Randomized Control trial. JAMA 2002; 288:321-333.
Love S. Doctor Susan Love's Hormone Book. San Francisco: Random House 1997.
Hays J, Ockene JK, Brunner RL, Kotchen JM, Manson JE, Patterson RE et al. Effects of estrogen plus progestin on health-related quality of life. N Engl J Med 2003; 348(19):1839-1852.
Beral V, Banks E, Reeves G. Evidence from randomised trials on the long-term effects of hormone replacement therapy. Lancet 2002; 360(9337):942-944.
Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Int Med 1991; 115:455-456.
Petitti DB. Hormone replacement therapy and heart disease prevention. Experimentation Trumps Observation (editorial). Journal of the American Medical Association 1998; 280:650-652.
Coronary Drug Project Research Group. Coronary drug project: findings leading to the discontinuation of the 2.5 mg/day estrogen group. Journal of the American Medical Association 1973; 226:652-657.
Prior JC. Critique of estrogen treatment for heart attack prevention: the nurses' health study. A Friend Indeed: for Women in the Prime of Life 1992; VII:3-4.
Prior JC. One voice on menopause. J Am Med Women Assoc 1994; 49:27-29.
Kreiger N, Sloan M, Cotterchio M, Kirsh V. The risk of breast cancer following reproductive surgery. Eur J Cancer 1999; 35:97-101.
Kolata G, Petersen M. Hormone Replacement Study a Shock to the Medical System. July 10, 2002, 1-5. 2002. New York, New York Times.
Grady D. A 60-year-old woman trying to discontinue hormone replacement therapy. JAMA 2002; 287:2130-2137.
Kaufert PA. The perimenopausal woman and her use of the health services. Maturitas 1980; 2:191-205.
Santoro N, Rosenberg J, Adel T, Skurnick JH. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab 1996; 81:4,1495-1501.
Prior JC. Perimenopause: The complex endocrinology of the menopausal transition. Endocr Rev 1998; 19:397-428.
Martin E. Medical metaphors of women's bodies: menstruation and menopause. Int J Health Serv 1988; 18:237-254.
Hale GE, Hitchcock CL, Williams LA, Vigna YM, Prior JC. Cyclicity of breast tenderness and nighttime vasomotor symptoms in midlife women: information collected using the daily perimenopause diary. Climacteric. 2003.
Prior JC, Vigna YM, Barr SI, Rexworthy C, Lentle BC. Cyclic medroxyprogesterone treatment increases bone density: a controlled trial in active women with menstrual cycle disturbances. Am J Med 1994; 96:521-530.
Speroff L. It's time to stop using the word 'replacement'. Maturitas 2000; 34:1-3.
Prior JC. Menopause. In: Gray J, Johnson G, editors. Therapeutic Choices. Ottawa, Ontario, Canada: C.K. Productions, 1995: 468-477.
Lindenfeld EA, Langer RD. Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial. Obstet Gynecol 2002; 100(5 Pt 1):853-863

What the Women’s Health Initiative Results Mean for Breast Cancer Survivors

Elyse — Fri, 09 Nov 2007 15:25:09 -0600

In July 2002 a large, randomized control trial called the Women’s Health Initiative was stopped three years early with the conclusion that Estrogen plus Progestin (E+P) is, on balance, not an effective preventative medication for healthy menopausal women. The results of this trial have surprised both doctors and the general public, because they have shown that E+P does not prevent heart disease and causes breast cancer (1). We believe there are several changes in concepts about menopausal hormone therapy that are important for breast cancer survivors.

The first change since the results of the E+P study is the knowledge that healthy, naturally menopausal women don’t need any hormone therapy to prevent heart disease. The E+P study showed an increase in heart attacks in those on hormones. Why did we formerly think that estrogen prevented heart attacks? Because the women who took estrogen in the non-randomized studies were healthier and had better lifestyles (2)! The combined results of the past studies and the E+P randomized trial lead to the conclusion that women’s risk for heart attack can be decreased by 80 percent by regular exercise, achieving and maintaining normal weight, not smoking, and treatment of abnormal blood lipids, high blood pressure and blood sugars. That means that breast cancer survivors who avoided estrogen therapy were not missing out on any heart preventive benefits!

The results of the E+P study say that menopause itself does not need treating. However, what has happened when the eight thousand study participants on estrogen plus progestin were told to suddenly stop their hormone therapy is that some developed severe night sweats and hot flushes (vasomotor symptoms, VMS). Now many more women and their doctors appreciate the misery from suddenly stopping estrogen. Many women who became menopausal due to breast cancer treatment already understand this! VMS caused by suddenly stopping estrogen are some of the most intense and difficult to treat.

There are some other recent developments in research on stress, enzymes and hormones that are relevant to breast cancer survivors struggling with hot flushes. Women having intense, persistent, sleep-disturbing night sweats are living with very high levels of adrenal stress hormones (3), some of which are converted into estrogen by the aromatase enzyme. New results from trials of drugs that inhibit aromatase in breast cancer survivors show improved breast cancer outcomes indicating that this is important. Therefore preventing the production of these stress hormones and the misery of night sweats takes on a new importance for breast cancer survivors.

But, you say, what effective therapies are available to treat hot flushes and night sweats in women with breast caner? The first is to prevent vasomotor symptoms in the first place—never stop estrogen suddenly. All women being treated with estrogen who need to stop it should do it very gradually over about four months. Daily full-dose progesterone therapy (Prometrium 300 mg at bedtime or medroxyprogesterone 10 mg/d) assists in the process of stopping estrogen without causing recurrent hot flushes. The Centre for Menstrual Cycle and Ovulation Research website (www.cemcor.ubc.ca) has information about gradually decreasing and stopping estrogen therapy. Vasomotor symptoms can be improved by stress reduction, and by treatment with progesterone and some progestins.

We believe that there are several important and non-harmful therapies to treat night sweats and hot flushes for the breast cancer survivor. The first is to take up relaxation therapy, yoga breathing (4) or mind-body therapy. All of these have been shown in controlled trials to improve night sweats and hot flushes. Treatment of depression with an antidepressant will also decrease stress hormones and may help night sweats. The importance of decreasing stress hormones as a treatment for VMS is only now becoming clear. And, given the aromatase inhibitor therapy results, reducing stress hormones should also help prevent breast cancer recurrence.

The second effective therapy for night sweats is progesterone or non-male hormone like progestins (such as medroxyprogesterone or megestrol (5)). A study we did some years ago showed that medroxyprogesterone (10 mg/d) is as effective as conjugated equine estrogen (0.625 mg/d) in control of vasomotor symptoms (6) Oral micronized progesterone has the added advantage that it assists with sleep (7).

The next question is, are progesterone or non-androgenic progestins safe for breast cancer survivors? The results of non-randomized trials in the past have suggested that progesterone added to the increased breast cancer risk from estrogen therapy. However, progesterone is used to treat high estrogen side effects such as bleeding and breast tenderness. This means there is a bias in these studies because only women with highest estrogen exposure would be given progestin. Based on better-designed studies, we believe that progesterone is safe for breast cancer survivors.

First, two large studies show that premenopausal women who have too little progesterone (lack of ovulation) but enough estrogen have higher breast cancer risk (8,9). The strongest data are from two randomized, placebo-controlled studies of the women’s breast cell changes in response to estrogen or progesterone therapy. Briefly, in both studies the breast cells of women who were taking progesterone showed markedly less proliferation (which is associated with increased cancer risk) than the cells of women on estrogen (10,11). All of these studies are consistent with the idea that progesterone controls the estrogen-related breast cell growth that carries a risk for cancer. Therefore we believe that progesterone is both safe and effective therapy for women breast cancer survivors with severe night sweats that relaxation therapy doesn’t adequately control.

In summary, the results of the first large controlled study of “hormone replacement therapy” for healthy menopausal women provide good news for breast cancer survivors. The first is that good lifestyle, not estrogen treatment prevent heart disease. The second is an increased awareness of the disability caused by severe night sweats that occur when estrogen therapy is suddenly stopped. From other recent studies we now know that the high stress hormones caused by having severe night sweats probably carry an increased risk for women with breast cancer. Finally, from well designed studies we now know that progesterone is both safe and effective therapy for severe night sweats in breast cancer survivors.

References

Writing Group for the Women's Health Initiative Investigators: Risks and benefits of estrogen plus progestin in health postmenopausal women: principle results from the Women's Health Initiative Randomized Control trial. JAMA 2002; 288: 321-333.
Barrett-Connor E: Postmenopausal estrogen and prevention bias. Ann.Int.Med. 1991; 115: 455-456.
Genazzani AR, Petraglia F, Fachinetti F, Facchini V, Volpe A, Alessandrini G: Increase of proopiomelanocortin-related peptides during subjective menopausal flushes. Am.J.Obstet.Gynecol. 1984; 149: 775-779.
Freedman RR, Woodward S: Behavioral treatment of menopausal hot flushes: evaluation by ambulatory monitoring. Am.J.Obstet.Gynecol. 1991; 167: 436-439.
Quella SK, Loprinzi CL, Sloan JF, et al: Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes. Cancer 1998; 82: 1784-1788.
Prior JC, Alojado N, Vigna YM, Barr SI, McKay DW: Estrogen and progestin are equally effective in symptom control post-ovariectomy--a one-year, double-blind, randomized trial in premenopausal women. Program of the 76th Annual Meeting of the Endocrine Society, Anaheim, Ca. 1994; Abstract 12H: 411(Abstract)
Friess E, Tagaya H, Trachsel L, Holsboer F, Rupprecht R: Progesterone-induced changes in sleep in male subjects. Am.J.Physiol. 1997; 272: E885-E891
Cowan LD, Gordis L, Tonascia JA, Jones GE: Breast cancer incidence in women with a history of progesterone deficiency. Am.J.Epidemiol. 1981; 114: 209-214.
Coulam CB, Annegers JF, Kranz JS: Chronic anovulation syndrome and associated neoplasia. Obstetrics and Gynecology 1983; 61: 403-407.
Chang KJ, Lee TTY, Linares-Cruz G, Fournier S, de Lignieres B: Influence of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil.Steril. 1995; 63: 785-791.
Foidart J, Collin C, Denoo X, et al: Estradiol and progesterone regulate the proliferation of human breast epithelial cells. Fertil.Steril. 1998; 5: 963-969.

Estrogen Deficiency: The Wrong Idea About Menopause

Elyse — Fri, 09 Nov 2007 13:37:45 -0600

The largest and best-controlled trial testing whether hormone “replacement” therapy prevented heart disease was stopped three years early in July 2002. The Women’s Heath Initiative (WHI) study included over 16,600 healthy menopausal women without symptoms. These women were randomized to daily conjugated equine estrogen (Premarin, 0.625 mg) plus medroxyprogesterone (Provera, 2.5 mg) or an identical placebo. Hormone therapy increased breast cancer significantly (by 26% over placebo) and caused higher rates of heart attacks (29%), strokes (41%) and blood clots (211%). These risks outweighed this therapy’s significant benefits in preventing osteoporotic fractures of the hip (decreased by 34%) and colon cancer (decreased by 36%).

Menopause (the phase of life beginning one year after the last period) is often viewed as a symptomatic and health-destroying event. Instead menopause is both natural and a welcome relief. Menopause is graduation from 30-40 years of the ovary’s cyclic hormonal demands. I think that the transition into menopause (called “perimenopause”) is the difficult time. I call perimenopause “estrogen’s storm season”!

Since July 2002,hundreds of talk shows and editorials across North America have discussed these results. Many doctors and medical groups have offered criticisms. The usual response is that estrogen and progestin should only be used for bad hot flushes. What is clear is that these Women’s Health Initiative results are hard for established medicine to swallow. However, no one has yet identified what I believe is most important.

What is the most important change since this study?

I believe that the most important change since the Women’s Health Initiative is to view menopause as a normal part of every woman’s life rather than an estrogen deficiency condition. As the late Mary O’Brien, a Canadian nurse-midwife and philosopher, said “it is . . . within the total process of human reproduction that the ideology of male supremacy finds its roots and its rationales."

The results of the Women’s Health Initiative require that society no longer view menopausal women as “estrogen deficient” and therefore needing “estrogen replacement.” Menopause is as normal for women as a period or being pregnant (if we choose). I once joked that calling menopause an estrogen deficiency disease is like saying a headache is an "aspirin-deficiency” condition.

It is important to realize that a fundamental change in the way we see things is difficult for everyone -- for experts, for physicians -- as well as for women.

Why did we believe that estrogen prevented heart disease?

Most scientist believed that estrogen prevented heart disease in menopausal women because many studies showed that thousands of women taking estrogen compared to women not taking estrogen had 30-50 per cent fewer heart attacks. The majority of the studies showed the same good result.

We now know that the women who took estrogen were healthier. This is called a “healthy cohort bias.” Women on estrogen were more likely to be physically active and were less likely to smoke, to be overweight, to have abnormal cholesterol levels, high blood pressure or diabetes. It was these healthy lifestyles, not estrogen treatment, which prevented heart disease.

This is a good news story. It means that living healthy lives prevents the majority of heart attacks in women. There is a 29 per cent increase in heart attacks from estrogen therapy. Healthier women in the observational studies had 30-50% fewer heart attacks. Healthy lives decrease women’s risk for heart attack. This means regular activity (I recommend 30 minutes of walking every day), not smoking, eating right to prevent abnormal cholesterol and blood sugar levels and high blood pressure. Effective treatments are available if, because of inherited risks, a good lifestyle is not sufficient.

Could we have known that estrogen caused heart attacks before this study?

Yes. Two randomized, controlled studies in men who had heart attacks tested the idea that estrogen there would prevent further heart disease. These were also stopped early because the men on estrogen experienced more heart attacks and blood clots. A randomized controlled trial of estrogen plus progestin therapy in women who already had heart disease also showed no improvement on hormone therapy. "As a scientist, I had, long before the recent results, questioned the notion that estrogen prevents heart disease."

Should doctors stop prescribing or women stop taking ovarian hormone therapy (OHT)?

That doesn’t make sense! Although we now know that healthy menopausal women without or with bearable night sweats don’t need treatment, some menopausal women would benefit from OHT. Estrogen and progesterone are the most effective therapies we have for night sweats or hot flushes that are disturbing.

A woman who has survived breast cancer, even if she has hot flushes and night sweats, should not take estrogen. However, I believe that progesterone is safe for her. Even progesterone should only be used if she is disturbed by her symptoms. Two randomized double blind trials of balanced hormone doses of progesterone, estrogen, estrogen with progesterone and a placebo were applied as a crème to one of each woman’s breasts. After 11 days of treatment, a small amount of tissue was removed from the treated breast and analyzed for the cell growth rate as a marker of the risk for cancer. Estrogen increased but progesterone decreased breast cell growth. Estrogen with progesterone also showed decreased growth. These results suggest that progesterone would decrease the risk for breast cancer.

Are there any good reasons to take ovarian hormone therapy?

There are three good, scientific and justifiable reasons for ovarian hormone therapy (OHT). Night sweats that that are chronic and disturbing are the first good reason for OHT. These may sufficiently disturb women’s well-being and metabolism that, like chronic pain, they require treatment. Night sweats may also be detrimental for bone and increase the risk for osteoporosis.

A woman with early menopause (before age 40 or 45 whether because of surgery, radiation or for other reasons) has missed out on part of the normal 30 to 40 years of cyclic high estrogen and progesterone levels. She needs balanced ovarian hormone therapy until she reaches age 51, the average age for menopause. Then she can begin tapering estrogen treatment.

Osteoporosis, broken bones with little force (like a fall from a standing height or less) and the bone loss that normally occurs during the years after menopause can be prevented by estrogen with progesterone therapy. And we now know OHT prevents hip as well as the more common back (vertebral) and wrist and ankle fractures. Osteoporosis at the time of menopause, especially if she also has severe hot flushes/night sweats is the third and final good reason for OHT.

Have you changed how you prescribe ovarian hormone therapy since WHI?

Yes. I will never again prescribe estrogen as a pill. When a pill of estrogen is swallowed it travels through the stomach to the liver and stimulates it to make new proteins. Some of these increase the risks for blood clots, others increase the risks for high blood pressure or migraine headaches. Evidence suggests (although we don’t have randomized controlled trial results) that estrogen absorbed through the skin (called “transdermal” as patch, crème or gel) will carry less risk. Progesterone and medroxyprogesterone have been tested over and over and never been shown to increase blood clots.

I continue to recommend that no one take estrogen for more than four or five years. This has been my practice for at least ten years. However, as discussed above, women with early menopause can safely take estrogen therapy until they reach age 51. In contrast to the time limit on estrogen, I believe that progesterone or medroxyprogesterone are safe for as long as they are needed.

I’ve decided to stop estrogen therapy. How should I do it?

If you have ever had hot flushes, I would recommend stop estrogen very gradually over three or four months and while taking full dose, daily progesterone. If you have osteoporosis or low bone density, you need to start etidronate or another bisphosphonate anti-bone resorption medicine before tapering estrogen (see Stopping Estrogen Therapy).

When you have been off the estrogen for several months, if you have no reason for progesterone (such as night sweats or low bone density) you could also stop progesterone.

Do you agree with giving estrogen without progesterone following a hysterectomy?

No. That idea doesn’t make sense—progesterone and estrogen work together in the normal menstrual cycle and in every tissue. In menopause, progesterone should always be used whenever estrogen is taken. Even if she is without her uterus, a menopausal woman continues to have breasts, bones and a brain that need progesterone.

Progesterone therapy should be taken daily and in a full dose to oppose the tendency of estrogen to cause cells to grow (proliferate and increase cancer risk). In bones estrogen slows bone loss, however, progesterone acts to stimulate bone growth (formation). Estrogen plus low dose progestin causes a greater increase in spinal bone density than estrogen alone.

How would you sum up your thoughts about Ovarian Hormone Therapy?

The first big controlled trial of OHT was stopped early because pill estrogen and low dose medroxyprogesterone therapy were not safe in healthy menopausal women. This proves that menopause is a normal part of life, not estrogen deficiency and doesn’t need hormone treatment. However, there remain three good reasons for menopausal ovarian hormone therapy—early menopause, osteoporosis with night sweats, and disturbing hot flushes/night sweats. If you have been taking estrogen for the wrong reasons or for longer than five years and want to stop, with the help of full dose daily progesterone and the estrogen patch you can stop it gradually over about four months.

Get more information from these articles:

Writing Group for the Women's Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative Randomized Control trial. JAMA 2002; 288: 321-333.

Prior JC: Perimenopause: the complex endocrinology of the menopausal transition Endocr.Rev. 1998; 19: 397-428.

O'Brien M: The politics of reproduction. London: Routledge and Kegan Paul, 1981; 1-240.

Prior JC: One voice on menopause. J.Am.Med.Women Assoc. 1994; 49: 27-29.

Prior JC: Critique of estrogen treatment for heart attack prevention. A Friend Indeed 1992; VII: 3-4.

Coronary Drug Project Research Group: Initial findings leading to modifications of its research protocol. J Am Med Assoc 1970; 214: 1303-1313.

Coronary Drug Project Research Group: Findings leading to the discontinuation of the 2.5 mg/day estrogen group. J Am Med Assoc 1973; 226: 652-657.

Hulley S, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. J Am Med Assoc 1998; 280: 605-613.

Prior JC: Postmenopausal estrogen therapy and cardiovascular disease (letter) N Engl J Med 1992; 326:705-6

Foidart J, et al: Estradiol and progesterone regulate proliferation of human breast epithelial cells. Fertil.Steril. 1998; 5: 963-9.

Chang-King J et. al. Influence of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil.Steril. 1995; 63: 785-791.

Lindsay R et. al. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. J Am Med Assoc 2002; 287: 2668-2676.

The Death of Hormone Replacement Therapy — Why and how to use Ovarian Hormone Therapy

Elyse — Wed, 07 Nov 2007 17:56:27 -0600

A response to the cancelled Women’s Health Initiative study and call for a healthier look at menopause

Dr. Jerilynn C. Prior, Scientific Director of the Centre for Menstrual Cycle and Ovulation Research, has never advocated the use of hormones as an ongoing “replacement” for menopause. She does not feel that menopause is a medical condition that needs to be “fixed”. Rather it is a normal stage of life. She strongly advocates use of new term for the few women who do need therapy in menopause. The new term is: Ovarian Hormone Therapy. Dr. Prior says there are only three main reasons for recommending OHT for a menopausal woman:

if a woman is experiencing early menopause (<40 or <45 with hot flushes or low bone density);
hot flushes are disturbing, especially when they interfere with sleep;
for treatment of osteoporosis especially in women with hot flushes.

For hot flushes progesterone, like estrogen, is effective. Dr. Prior also states OHT should only be taken longer than five years if menopause came too early. She has never advocated OHT for prevention of heart disease.
Dr. Prior believes menopause is a normal part of a woman’s life cycle. It is not, in general, something that needs medical “treatment.” She prefers the term “ovarian hormone therapy” because it more correctly describes treatment for those who need it. Some women do have sufficiently disturbing hot flushes or osteoporosis that short term treatment is appropriate.

Be sure to read Dr. Prior’s article “Estrogen Deficiency: The Wrong Idea About Menopause” also found on this site. Click here for more detailed information about the early curtailment of the WHI study and Dr. Prior’s thoughts on when and why to use ovarian hormone therapy.

Stopping Estrogen Treatment (Sometimes called “HRT”)

Elyse — Wed, 07 Nov 2007 17:35:08 -0600

In July 2002, the largest randomized placebo-controlled study of “Hormone Replacement Therapy” for healthy menopausal women was stopped early because it showed that estrogen plus very low dose medroxyprogesterone therapy caused serious harm. Women, when they learned of these results, suddenly stopped their hormone therapy. Many found themselves dealing with severe night sweats and hot flushes. The Centre for Menstrual Cycle and Ovulation Research believes you can stop estrogen and avoid the hot flushes. Here's how:

Slowly Does It

Some women who abruptly stop estrogen therapy will have bad hot flushes that can be very hard to treat. Tapering the medication over time can prevent this.

Note: If you have osteoporosis, you should ask your doctor for a prescription for Etidronate as Didrocal®. This works like estrogen to prevent bone loss. Start taking Etidronate before you begin tapering estrogen treatment

Steps To Coming Off Slowly

A. Increase to a full dose of progesterone:

300 mg of oral micronized progesterone (Prometrium® or compounded progesterone pills) per day, taken at night, OR
10 mg of medroxyprogesterone acetate (Provera) per day

You can try progesterone cream, but the appropriate dose is not yet known. The dose will be approximately 150 mg twice a day.

I recommend oral micronized progesterone (Prometrium® or compounded progesterone pills) because it will help with hot flushes as well as aid sleep.

B. Gradually decrease the estrogen you are taking.

Ideally, switch to a transdermal (patch or gel form) of estrogen, which allows you to decrease more gradually. This is especially important if you have ever had hot flushes. However, this is slightly more expensive than the pill form. If you can't afford the patch or gel, see the pill schedule below. Decrease over about four months. You can cut the patch to decrease the dose. Be sure to save the pieces you cut off for later use.

1. Here is an example of how to decrease the estrogen using a patch, over 14 weeks.

Weeks 1-2

7/8 of a patch

Weeks 3-4

3/4 of a patch

Weeks 5-6

5/8 of a patch

Weeks 7-8

1/2 a patch

Weeks 9-10

3/8 of a patch

Weeks 11-12

1/4 of a patch

Weeks 13-14

1/8 of a patch

Week 15

off estrogen

2. Here is an example of how to decrease Conjugated Estrogen (Premarin (CEE) or CES) over 3 months:

Ask your health care provider for a three-month prescription of the lowest dose (0.3 mg, green tablet) of Conjugated Estrogen. Most women have been taking the standard dose (0.625 mg, burgundy tablet).

Week 1: 0.625 on 6 days, 0.3 on 1 day

Week 2: 0.625 on 5 days, 0.3 on 2 days

Space out the pills. Rather than having all 0.625 mg pills in a row, then all 0.3 mg, space them out evenly. For example:

Monday

Tuesday

Wednesday

Thursday

Friday

Saturday

Sunday

0.625

0.625

0.3

0.625

0.625

0.3

0.625

Week 3: 0.625 for 4 days, 0.3 for 3 days

Week 9: 0.3 for 5 days

Week 4: 0.625 for 3 days, 0.3 for 4 days

Week 10: 0.3 for 4 days

Week 5: 0.625 for2 days, 0.3 for 5 days

Week 11: 0.3 for 3 days

Week 6: 0.625 for 1 day, 0.3 for 6 days

Week 12: 0.3 for 1 day

Week 7: 0.3 for 7 days

Week 13: Off estrogen

Week 8: 0.3 for 6 days

3. Here's an example of how to taper and stop estrogen therapy in a gel form (Estragel®).

If you have been on a high dose of pill estrogen (more than 0.625 mg/day) you will need to start with two pumps of Estragel® each day. For the two weeks use two pumps per day, except that one day a week decrease to one pump. The next two weeks use one pump every third day. Then alternate one and two pumps a day for a couple of weeks. Now use one pump a day for two weeks.

You are now ready to taper down to less than one pump a day. To do this you need to figure the length of gel in a full pump so you can gradually decrease by about 10% every couple of weeks. First, slowly push out one full pump of estradiol gel making an even bead on a heavy piece of paper. You want to stretch out the gel as evenly and as far as you can. Then mark the beginning and the end of this line of gel with a pen—it will be about 6 cm or a little over two inches. That is 100% of a dose. Now take a ruler and divide that line into 10 parts. You will decrease from 100% to 90% and take this for two weeks before decreasing to 80%. Keep on this schedule until you are off of Estragel® entirely.

C. What to do if the hot flushes start again as you taper estrogen therapy

If you start getting increased hot flushes or night sweats as you are lowering your dose of estrogen, go back up to the level of estrogen at which hot flushes were totally gone. Maintain that dose for several weeks longer before beginning to gradually reduce the dose again.

D. What to do about the progesterone therapy when you are off estrogen

If you have successfully stopped estrogen and have no hot flushes, you may wish to stop progesterone also. Progesterone does not need to be tapered. If the hot flushes start, then you need to continue. Try stopping progesterone once a year. Or you may decide that progesterone is also helping your bones (see ABCs of Osteoporosis Treatment) and stimulating osteoblasts to build new bone. You may also find it helps your sleep and that you would like to continue it. You can safely do that (see Progesterone Therapy for Menopausal Women). Natural progesterone does not cause blood clots and, based on its scientific actions in tissues, it is more likely to prevent breast cancer and heart disease than to cause them.

Weeks 1-2	7/8 of a patch
Weeks 3-4	3/4 of a patch
Weeks 5-6	5/8 of a patch
Weeks 7-8	1/2 a patch
Weeks 9-10	3/8 of a patch
Weeks 11-12	1/4 of a patch
Weeks 13-14	1/8 of a patch
Week 15	off estrogen

Monday	Tuesday	Wednesday	Thursday	Friday	Saturday	Sunday
0.625	0.625	0.3	0.625	0.625	0.3	0.625

Week 3: 0.625 for 4 days, 0.3 for 3 days	Week 9: 0.3 for 5 days
Week 4: 0.625 for 3 days, 0.3 for 4 days	Week 10: 0.3 for 4 days
Week 5: 0.625 for2 days, 0.3 for 5 days	Week 11: 0.3 for 3 days
Week 6: 0.625 for 1 day, 0.3 for 6 days	Week 12: 0.3 for 1 day
Week 7: 0.3 for 7 days	Week 13: Off estrogen
Week 8: 0.3 for 6 days