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WHI, Five Years Later–WHY no Change

It has been five years since the Women’s Health Initiative (WHI) Estrogen plus Progestin (E plus P) trial was prematurely stopped because it caused harm (1). Until the Estrogen in women with hysterectomy arm (E only) of the WHI was also halted prematurely in 2004 (2), progestin was blamed for the lack of heart disease prevention. But now, five years later, doctors and media are still discussing Hormone Replacement Therapy (HRT) and menopause as estrogen deficiency. Only now the hype is: "WHI was wrong about estrogen preventing heart disease because the treated menopausal women were too old!" (How 'bout HRT at 40? Or 20?) The fundamental question is: Given these huge, great science WHI studies showing harm is caused by HRT, why has medicine not changed?

Here’s my guess for the answer: Because the fundamental, negative ideas about women have not changed. The wrong idea–menopause-means-estrogen-deficiency, not menopause-is-normal-inevitable-as-tides-and-seasons–is still dominant. These deficiency/disease ideas, despite our supposed egalitarian society in the 21st century, are based on a strong, imbedded cultural belief that women are inferior.

The purpose of this article is to outline the prejudice against women on which medicine’s concepts of "menopausal estrogen deficiency" and "hormone replacement" are based, to identify the ways these ideas are unscientific, and to propose some things we can do to cause constructive change for women.

First, a personal word. I am deeply offended by the lack of change in medical concepts about menopause. I am a specialist physician who considers it my life’s work to do research, to work with women, to teach and to create new science about women’s ovarian hormones and reproduction. For over twenty years I have been saying that menopause is a natural part of women’s life cycle. I’ve been insisting that the low estrogen levels after menopause are healthy, not abnormal. This made me unpopular with my medical colleagues. Therefore the WHI results that E plus P and E alone caused cardiovascular disease was a vindication–I had predicted that result 10 years earlier (3). Further, a meta-analysis of many controlled trials shows net harm from HRT (4).

The apparently positive responses of menopausal women to HRT (in huge but poor-design studies) were the keystone in the arch of what I believe is a societal reproduction-based prejudice against women (Figure 1). With WHI’s destruction of that keystone, the arch should crumble. If Science and Medicine were science-based, all of the similar prejudice-based ideas and therapies would be challenged and replaced. But the arch has held. This new science did not change ideas and medical practice because there are still strong, negative cultural ideas about women in this society. The five-year results of the WHI randomized controlled trials provide evidence-based proof of misogyny.

Figure 1

What does "misogyny" mean? In Norwegian, misogyny roughly translates to "woman hating." Misogyny means that women are being treated badly. Women’s reproductive life cycle is considered "diseased" because it differs from the life cycle for men. The figure below contrast the life cycles of estrogen for women and testosterone for men.

Life cycle of estrogen and testosterone

Figure 2

It is obvious to me and to many women–we are normally different. We have babies, we bleed, and we go through perimenopause’s higher, chaotic estrogen levels into the calm of low menopausal estrogen levels. All of this is normal and natural. Men’s normal testosterone levels, although they decline somewhat in older ages, never become low. From this comparison rises the concept of "menopausal estrogen deficiency." And from that follows the HRT 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!" (5).

The strongest evidence for the belief that menopausal women are estrogen deficient has been that estrogen treatment apparently decreased heart attacks by 50% (6). Estrogen also was formerly touted as preventing dementia, incontinence and markedly improving women’s quality of life. Dementia (7;8) and incontinence (9), however, are caused or orsened by menopausal hormone therapy. And quality of life did not change with E plus P (10). I still believe what I impulsively said when being interviewed. In the early 1990s on "The Best Years," I responded to Joyce Resin quoting Dr. M. Gelfand that estrogen improved women’s quality of life, by blurting, "Better quality of life with estrogen is a smoke-screen for keeping women diseased and dependent." It’s not that I don’t know about and treat heavy bleeding, premenstrual sadness, cramps and perimenopausal misery. It’s not that I don’t know that severe night sweats are intolerably miserable–I have had personal experience. To deal with hot flushes and night sweats, I have shown in a double blind one year study, that medroxyprogesterone is as good as estrogen, the gold standard (11).

Since the 1930s, with the help of companies manufacturing hormones, the opinion of doctors has been that estrogen therapy is good for women. The pharmaceutical companies making estrogen have played very strong roles 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. So strong was the belief that estrogen therapy prevented heart disease in menopausal women that a medical professor, and leader in a large and reputable disease-focused organization in Canada demanded that I say so when invited to talk at a forum on Menopause and Osteoporosis in Toronto. When I protested that there was no randomized, controlled trial evidence for estrogen as heart disease prevention, I was told I "had" to say it!

I ended up compromising. I told the women at that forum: "most physicians believe that estrogen prevents heart disease. I won’t believe that until we have randomized double blind placebo-controlled trial evidence proving it." WHI didn’t prove it. And, long before, a randomized placebo-controlled estrogen trial in men was stopped years early because it showed that estrogen treatment caused heart, blood clots and other serious risk (12). Results from that study should have triggered similar controlled trials in women. Instead, that disastrous study in men was virtually ignored, and hundreds of observational studies (a less scientific design) were funded, conducted and published. Meanwhile, millions of healthy menopausal women around the world have been taking hormone "replacement" therapy to prevent disease. Only concerted effort by science-based feminist groups (such as the National Women’s Health Foundation in the USA) and the collective writings of skeptical feminists (5;13;14) caused the National Institutes of Health in the USA to fund the WHI.

The WHI hormone trials were designed to test the belief that HRT prevented diseases in healthy menopausal women (of the ages of women being treated for that reason in the USA at the start of the study) without severe hot flushes and night sweats, heart disease, osteoporosis or breast cancer. 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 while preventing osteoporosis (1). E in hysterectomized women also caused strokes and blood clots, did not prevent heart disease, but prevented osteoporosis (2).

In being asked about the WHI’s discontinuation Dr. Utian, executive director of the North American Menopause Society, said, "It’s not just a matter of what the data says–truth is opinion" (15). He means his opinion and that of the thousands of academic pharmaceutical company-funded gynecologists that have been controlling concepts in women’s health for decades. He is counting on societal prejudice to spin WHI results until no harm remains.

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 had stopped hormone therapy (16). That led to severe hot flushes in hundreds of thousands of women, in at least half of all women who had previously experienced them. Because it is well known that rapid withdrawal of estrogen treatment can cause worsening of original 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. Without helpful information, and because night sweats/hot flushes are so soul-destroying miserable, many women, in desperation, have reluctantly restarted estrogen even though they don’t want to take it (17).

So, let’s get back to WHI, menopause, evidence-based medicine and misogyny. I believe that we have a unique opportunity, right now, as women at this fifth anniversary of the initial WHI results. We must call attention to the negative ideas about women that are part of our culture and that the responses to the WHI results so clearly illustrate. 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. For me, menopause was "graduation." As a menopausal woman I truly feel freed–I’ve survived the premenopausal demands of cyclic estrogen and the chaos of perimenopause. I’ve weathered "estrogen’s storm season" (18). As women it is now time to declare that the estrogen deficiency concept of menopause is wrong, is based on prejudice, and not on science.

Let’s not forget women as we focus on prejudice. Although HRT is harmful for healthy menopausal women without symptoms, ovarian hormone therapy (OHT) continues to be an important and physiological treatment for women whose menopause came early (before age 40 or perhaps 45), for menopausal women with osteoporosis plus moderate to severe hot flushes (19) and for women with disturbing night sweats causing chronic sleep disruptions. Remember, that for night sweats alone, progestin is as good as estrogen (11) (and probably safer and easier to stop). 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 doses that match those occurring in the normal menstrual cycle, and taken 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 daily doses of estrogen and progesterone that are equally balanced, menopausal women usually have no further vaginal flow. However, with the full dose estrogen and very low dose progestin treatment, the doses 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 compared with placebo-treated women (1). This unpredictable, abnormal bleeding, which planners should have known would occur, based on evidence from an earlier randomized, controlled study (20), is further evidence of medicine’s misogyny. (Would an unpredictable penile discharge be considered a nuisance?)

Have I changed my thoughts and practice since WHI? I have always believed, taught and written that menopause is normal and that it is natural in menopause for estrogen and progesterone levels to be low. However, I will never again prescribe estrogen as a pill. WHI results show important harm from blood clots (increased by over 200 percent more than placebo). Evidence says to me that estrogen treatment delivered through the skin will be safer and less likely to increase the liver clotting proteins than estrogen taken by mouth that is first metabolized through the liver.

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 controlled trials of hormone therapy for prevention, 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 and progesterone levels are natural and healthy for those of us who have graduated into menopause. If we are symptomatic with early menopause, night sweats and osteoporosis then balanced physiological estrogen and progesterone is good ovarian hormone therapy and if we have sleep-disturbing night sweats, progesterone alone will be effective and safe.

What can we do?

  1. Change the language. I and others (21) 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. 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.
  2. Ensure research funding. We must pressure the Canadian Institutes of Health Research (CIHR) 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 double blinded, without knowledge of the identity of the authors.
  3. Recognize prejudice. 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!" Finally, say that these prejudicial ideas are unscientific.

Reference List

  1. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in health postmenopausal women: prinicpal results from the Women's Health Initiative Randomized Control trial. JAMA 2002; 288:321-333.
  2. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291(14):1701-1712.
  3. Prior JC. Postmenopausal estrogen therapy and cardiovascular disease (letter). N Engl J Med 1992; 326:705-706.
  4. 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.
  5. Love S. Doctor Susan Love's Hormone Book. San Francisco: Random House?, 1997.
  6. Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 1991; 20:47-63.
  7. Shumaker SA, Legault C, Thal L, Wallace RB, Ockene JK, Hendrix SL et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289(20):2651-2662.
  8. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291(24):2947-2958.
  9. Hendrix SL, Cochrane BB, Nygaard IE, Handa VL, Barnabei VM, Iglesia C et al. Effects of estrogen with and without progestin on urinary incontinence. JAMA 2005; 293(8):935-948.
  10. 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.
  11. Prior JC, Nielsen JD, Hitchcock CL, Williams LA, Vigna YM, Dean CB. Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy. Clin Sci (Lond) 2007; 112(10):517-525.
  12. 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.
  13. 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.
  14. Prior JC. One voice on menopause. J Am Med Women Assoc 1994; 49:27-29.
  15. Kolata G, Petersen M. Hormone Replacement Study a Shock to the Medical System. July 10, 2002, 1-5. 2002. New York, New York Times. Ref Type: Report
  16. Ockene JK, Barad DH, Cochrane BB, Larson JC, Gass M, Wassertheil-Smoller S et al. Symptom experience after discontinuing use of estrogen plus progestin. JAMA 2005; 294(2):183-193.
  17. Grady D. A 60-year-old woman trying to discontinue hormone replacement therapy. JAMA 2002; 287:2130-2137.
  18. Prior JC. Estrogen's Storm Season- Stories of Perimenopause. Vancouver,BC: CeMCOR, 2005.
  19. Prior JC. Menopause. In: Gray J, Johnson G, editors. Therapeutic Choices. Ottawa, Ontario, Canada: C.K. Productions, 1995: 468-477.
  20. 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.
  21. Speroff L. It's time to stop using the word 'replacement'. Maturitas 2000; 34:1-3.
Dr. Jerilynn C. Prior, Scientific Director, Centre for Menstrual Cycle and Ovulation Research
Life Phase: 
Perimenopause, Menopause
Updated Date: 
December 6, 2007

Estrogen’s Storm Season: Stories of Perimenopause

Estrogen's Storm Season

by Dr. Jerilynn C Prior

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