10/02/2013 08:38 pm ET Updated Jan 23, 2014

Hormone Replacement at Menopause: The Profound Importance of 'Maybe'

Last month, colleagues and I published what I consider a very important paper in the American Journal of Public Health, indicating that tens of thousands of relatively young women who have undergone hysterectomy are dying needlessly because of an over-generalized fear of hormone replacement. Publication in the current issue of The Journal of the American Medical Association (JAMA) of a rich compilation of findings from the Women's Health Initiative (WHI) trial does nothing to change our conclusions.

Our paper explains itself in clear detail for those who read the scientific literature. For everyone else, I have detailed our mission and our methods in online columns more than once. So I won't belabor those efforts now. But in a nutshell, published data from the WHI showed a decisive survival and health benefit for women who had undergone hysterectomy and took estrogen replacement in their 50s. There are roughly eight million women age 50 to 59 in the U.S. today who have undergone hysterectomy, so this is not a trivial matter.

The WHI data also showed harmful effects of estrogen replacement for older women. But there are two key considerations here. First, we have long known that treating with hormones soon after menopause has dramatically different effects than doing so a decade or two later. If this seems at all counterintuitive, consider an illustration: regular exercise can markedly reduce heart attack risk when administered "early," but exercise could well precipitate a heart attack when administered "late" to someone who already has advanced coronary disease. The analogy isn't perfect, but it's perfectly good enough.

The second consideration is that death is not the enemy -- premature death is the enemy. Dying within a decade of age 50 is a very different matter than dying within a decade of 70. The former is dying too young. The latter could well mean dying at the standard U.S. life expectancy. The potential survival advantage of estrogen replacement in younger women does not become less important just because of potential harmful effects in women a decade or two older.

An editorial accompanying the new paper in JAMA seems to reach the conclusion that the WHI is a decisive argument against hormone replacement for all women. The editorialist, however, while pointing out the importance of the WHI in helping overcome the "dogma" that hormone replacement was always good, seems to be replacing it with the countervailing dogma that hormone replacement is always bad. This just isn't so.

For starters, the WHI only studied one kind of hormone replacement, and not a preferred choice among my expert colleagues. The trial used CEE, or conjugated equine estrogens (yes, that is estrogen from horses) for their estrogen, and MPA (medroxyprogesterone acetate) for their progesterone. No other preparations were studied. This was justified because these were the most commonly used hormones years ago when the study began. Equine estrogen may differ enough from human estrogen to have at least some importantly different effects, however. MPA is a fairly high-potency synthetic progesterone, apt to induce more side effects than the variety truly native to us.

Then there's the fact, reaffirmed by the new JAMA paper, that the effects of hormone replacement vary considerably with the age of the women, along with the inclusion or exclusion of progesterone. Women who have had a hysterectomy -- and as noted, for better or worse millions of women in the U.S. have -- can take estrogen alone without progesterone.

My colleagues and I published our paper, and I have published my related columns, because we believe a small percentage, but still a very large number, of women are being harmed -- even killed -- due to an inappropriate aversion to the very concept of hormone replacement. We never said, and I am not saying now, that hormone replacement is good for all. Clearly, it isn't. We are not refuting the potential for harm, especially when progesterone is in the mix, and in general for older women.

We are simply saying that one size does not fit all, and doctors and patients need to discuss the matter without bias to reach the most salutary conclusion for any given individual. The data in the newly published paper fully support this contention, even if the editorial attached to the study disputes it.

We have varied results by age and personal characteristics for one very well-studied form of hormone replacement. We actually know far less about many other forms of hormone replacement, some of them much preferred by those with careers devoted to the matter. An out-of-hand dismissal of hormone replacement for any woman is a misinterpretation of what we know, and a potentially grave mistake. No less so than the universal endorsement that once prevailed. We are making no progress if we replace one version of misguided dogma with another.

Please -- my fellow clinicians and patients alike -- be open-minded, be well-informed and make personalized decisions accordingly. The WHI never generated an all-encompassing "no," and my colleagues and I are by no means defending a universal "yes." We are merely pointing out the profound importance of "maybe."


Dr. David L. Katz;

Dr. Katz is the author of the newly released Disease-Proof

Disease-Proof is available at bookstores nationwide and at:


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