Many menopausal women have abruptly stopped HRT for fear of the heart attacks, strokes, blood clots and breast cancer after publication of the large US Women’s Health Initiative Study. Now many women wake sweating, night after night, and are exhausted, and many more are worried, angry or confused. The purpose of this short piece is to explain how we came to the situation that hundreds of thousands of well women were taking a preventive therapy that turned out to cause harm. In addition, I hope to dispel worry and to offer non-harmful, effective therapy for early menopause, osteoporosis and night sweats/hot flushes.
First, we need to talk concepts and language. Women are obviously different from men ? our normal life cycle of hormones includes low estrogen and progesterone levels after menopause. However, for about six decades, medicine has taught us that having low menopausal estrogen was abnormal. Why? Because men’s high testosterone levels continue into old age (with a bit of a decline). Therefore, the idea that menopausal women were deprived of estrogen or ‘estrogen deficient’ became common. And ‘HRT’ was invented to fix women’s supposed problem.
But it wasn’t enough to say women were deficient’, this deficiency must cause disease. One early, important study, The Framingham Study, a decade-spanning observational study (meaning that the scientists observed what occurred over time) showed that when women reached menopause they started to have heart attacks. The authors noted that menopausal women have low estrogen levels. Therefore estrogen ‘deficiency’ must be the cause for heart disease! Of course, on average menopausal women were older, less active and heavier, too, but those facts were ignored.
The Framingham Study was followed by the huge Nurses’ Health Study that was another observational one. It showed that the women who took estrogen compared with the women who didn’t, had fewer heart attacks. However, women who took estrogen were slimmer, more active, less likely to smoke, less likely to have high blood pressure, abnormal blood cholesterol levels or diabetes. These characteristics, in addition to a family history, represent a woman’s main risks factors for heart attack. All of the observational studies, we now know, were biased’the women who took estrogen were healthier to start out with. Other similarly biased studies multiplied showing that women on estrogen had better sex, were less likely to get Alzheimer’s, grow wrinkles or fracture hips. ‘HRT’ became the wonder drug for women.
I don’t know quite why but I have never believed the estrogen deficiency idea of menopause. And I knew of the blood clots, strokes, high blood pressure and weight gain (for some) that estrogen therapy could cause. I also remembered a study of men who took estrogen or a placebo (sugar pill). The men taking estrogen had increased clots and heart attacks and the study was stopped early because of harm. This was in 1972. (Somehow the heart disease experts had forgotten that study). However, enough experts questioned the validity of the observational studies, that a very large multi-part, randomized, controlled trial called the Women’s Health Initiative was conducted. Results of the Women’s Health Initiative combined with several other controlled studies showed that one of every 250 women ages 50-59, and one of every 150 women over 60 taking estrogen treatment for five years will develop blood clots, stroke, heart attack or breast cancer.
But knowing this, what do we do now? First of all, accepting that low levels of estrogen after menopause are normal, means we don’t have to fear we’re missing out on some magic preventive. Instead we can concentrate on exercising, stopping smoking, getting to and keeping a normal weight, and (if needed) getting effective treatment for high blood sugar, blood pressure or cholesterol. There are now fracture-preventing non-hormonal treatments for osteoporosis such as etidronate (Didrocal), alendronate (Fosamax) and risedronate (Actonel). We can use very low dose vaginal estrogen or a compounded, safer kind of estrogen called estriol for vaginal dryness if over-the-counter lubricants don’t help.
And what about hot flushes? Relaxation, yoga, deep breathing and meditation decrease them significantly. Some of the newer anti-depressants and soy foods may also be effective. For severe hot flushes, relaxation combined with a synthetic progestin medroxyprogesterone (Provera) mean most women become virtually free of hot flushes. However, the pill form of natural progesterone that is the same as your ovaries made (bio-identical), Prometrium, is an effective option if you are worried that medroxyprogesterone might cause harm (because a low dose was used with full dose estrogen in one arm of the Women’s Health Initiative). The Centre for Menstrual Cycle and Ovulation Research (CeMCOR) at UBC and Vancouver Hospital is doing the first trial of Prometrium as treatment for hot flushes in a four-month placebo-controlled study in menopausal women. Because we are also studying blood vessel effects we are looking for women a year past their final period who have moderate or severe hot flushes and no risks for heart disease (for further information call 604 875-5917, email firstname.lastname@example.org or go to the website www.cemcor.ubc.ca).
What if you’ve re-started estrogen despite the bad news from the Women’s Health Initiative because you just couldn’t stand the hot flushes? As explained in ‘Stopping Estrogen Therapy’ on the CeMCOR website, the key is to take full dose progesterone to treat the symptoms while you very gradually taper and eventually stop your estrogen. Hot flushes are caused by the reaction of a brain that has become used to high estrogen levels. Therefore the process of effective withdrawal must be a slow one. Prometrium helps in the estrogen withdrawal process because it improves deep sleep (although this has only been proven in men!) and also treats hot flushes.
However, there are specific instances where menopausal women will need to take estrogen with progesterone therapy. These include women with early menopause (before age 40 for sure and probably before 45), women with both osteoporosis and hot flushes, and those with severe hot flushes not effectively treated by non-hormonal therapies. There are bio-identical choices for getting estrogen through the skin as a patch or gel (Estragel, Estradot and Climera, to name a few). These are less likely to cause clots than pill estrogen. Bio-identical progesterone is available as oral Prometrium (in peanut oil) or it can be compounded in oil by local pharmacies. Women with early menopause can safely continue estrogen and progesterone until they are 52 years old (the average age at menopause). Women with osteoporosis and hot flushes can count on combined hormones to treat hot flushes and prevent fractures. After five years estrogen should be replaced with a non-hormonal bone medicine (as described earlier). Women with severe hot flushes can use progesterone alone and (I believe) safely continue for as long as needed. Family doctors and women with questions will find more information on the CeMCOR website.
We are in a new and healthier world for women in 2004. We no longer need to rely on an old and wrong idea that menopausal women are estrogen deficient and need treatment. I think it is a good news story!
Jerilynn Prior is a Professor of Endocrinology at the University of British Columbia and an internationally know expert on women’s health.