Guest Post by Paula S. Derry, Ph.D.
Déjà vu
An article in today’s New York Times Magazine recounts the author’s experience with a debilitating depression that began during her perimenopause, the transitional time leading up to menopause. For her, prescription estrogen was a life-saver that alleviated her symptoms. The article places her experience in the context of research on the Timing Hypothesis, an idea that arose after the Women’s Health Initiative, or WHI, research project. WHI clinical trials documented that hormone supplements after menopause did not, as had previously been assumed, lower a woman’s risk of heart disease. Heart disease risk was not lower, and, in fact, when a number of chronic illnesses were considered together, the medication did more harm than good overall. The Timing Hypothesis is the idea that the WHI was fundamentally flawed, because hormones must be started right around the time of menopause to have a health-promoting effect and the subjects in WHI were on average over 60; if started when a woman is older, when chronic illnesses have already started, the hormones are actually harmful rather than helpful. The Sunday New York Times article presents this idea uncritically, without quoting any of the many experts who do not find it plausible or convincing, and, in addition, presents a lurid, unscientific description of perimenopausal hormonal dynamics with words like “ricocheting hormones” and an “upheaval” that causes a “hellacious strain” on the brain. The author suggests that WHI was a poorly planned study that asked the wrong questions with the wrong methodology. The Timing Hypothesis, if true, might lead to a cure for Alzheimers and have other important health repercussions.
Time for a reality check.
Let’s go back in time to before the WHI research. Beginning in the 1980s, professionals asserted that hormone therapies were safe and effective to prevent chronic illnesses, especially heart disease, in postmenopausal women. This idea was aggressively promoted, and it was not limited to women around the time of menopause. Clinical trials are required to prove that a new medication is safe and effective before the Food and Drug Administration will approve that medication. However, once approved and available on the market, it is okay for doctors to use their judgment and prescribe the drug for whatever use they believe is reasonable. Many of the claims for estrogen were for this kind of off-label use because there was no clinical trial proof that estrogens reduced heart disease, made women “feel better,” or improved their lives in many other ways being claimed. However, other kinds of evidence made it seem plausible. There were “biologically plausible” mechanisms–this means that because of things we know about the body–like the fact that there are estrogen receptors in the brain–it is plausible, we can hypothesize a way that estrogen would have a certain health effect. There were the personal experiences of women. There was the idea that menopause was intrinsically unhealthy and that women were not meant to “outlive their ovaries.” Using estrogens was compared by some to using vitamin supplements or to a diabetic using insulin. There was a strong conviction among certain enthusiastic scientists and practitioners, some of them highly respected individuals, that it was all so. Professional groups of various sorts frequently issue opinions about medications; here, many groups offered the opinion that all women be offered hormone treatment. Physicians were encouraged to prescribe hormones for disease prevention because it was so certain that it would help their patients, rather than waiting for the slow process of clinical trials to take place. Wyeth, a pharmaceutical company, asked the FDA to approve estrogen for heart disease prevention even without clinical trials.
