Misguidance at menopause

The United States Preventive Services Task Force has rendered a verdict of “D” for hormone replacement at menopause, inveighing against it. This is only a draft recommendation at this point, and we are in an open comment period. So here’s my comment: the Task Force got this one wrong.

Few topics in medicine have been so badly muddled as hormone replacement, or HR, at menopause. For many years, we were all quite confident in considerable, net benefits based on observational studies. During that era, we were surely mistaking some bathwater for the baby.

Then, when randomized trials, notably HERS and the WHI, were conducted, a small surfeit of harms were seen with HR. Note that the surfeit was, indeed, small, and the results of both trials showed a mix of harms and benefits, with no difference between intervention and control groups in total mortality. Rather, the WHI was stopped early once it was clear that hormone replacement was not on track to produce a statistically significant benefit overall.

How did a mix of benefits and harms, no overall mortality difference, and “not consistent with the requirements for a viable intervention for primary prevention of chronic diseases” get translated into a blanket recommendation against HR? By distorting the subtleties of the evidence into the customary and toxic brew that results routinely when medicine and the media cook together: hyperbole, oversimplification, and the banality of sound bites.

The media in general are devoted less to our edification and more to our fleeting but recurrent attention, and titillation. The prevailing mantra is “afflict the comfortable, comfort the afflicted.” This has direct implications for HR at menopause that have concerned me deeply for a decade or more, and is a general threat to understanding in the service of public health.

We had grown comfortable with the idea that HR reduced chronic disease risk, so a qualified reality check indicating that the matter was subject to considerable uncertainties was the truth, but a truth unsuitable for afflicting the comfortable. To afflict the comfortable, the media message needed to be: “hormone replacement will kill you now.” In 2002, there were many headlines along just such lines.

Another, more important matter was that only one very particular, and notoriously bad version of HR had been studied: the combination of horse (rather than human) estrogen (Premarin), with a high-potency, synthetic progesterone (Provera). By way of analogy, we might conduct a study of breathing oxygen at some concentration markedly different from that in our native atmosphere, tally the harms of oxygen toxicity, and issue a blanket recommendation against breathing the stuff. If you don’t immediately see the folly in that, I invite you to hold your breath until it comes to you.

There are much better preparations than “Prem/ Pro,” but that was not the biggest problem with the HR-is-bad-for-you-now conclusion. The biggest problem was that: women vary. All of the data on HR and health outcomes, viewed with careful attention to sub-groups, show a highly significant, age-related pattern. Women who replace ovarian hormones right at menopause derive considerable benefit; women who delay for a decade do not. Summary judgment that ignores this highly significant dichotomy is seriously deficient.

Also misguided is applying the questionable conclusion we have reached about combination HR (estrogen plus progesterone) to other forms of HR, namely estrogen alone. Women who have undergone hysterectomy, a population of some 20 million in the U.S., can take estrogen on its own. The WHI study showed that the use of unopposed estrogen in women with prior hysterectomy who took it early after menopause reduced mortality significantly. Worded differently: the fear of HR induced by our “afflict the comfortable” approach to medical news has killed tens of thousands of women prematurely, and needlessly, over the past decade and a half.

The wrong hormone replacement at the wrong time for the wrong women is sure to impose net harm. The right preparations at the right time for the right women are reliably beneficial. Much decision-making takes place between these obvious extremes, and such decisions should, like those for prostate cancer screening, issue from personal discussions between patient and provider.

Summary judgment against HR is unfounded, misguided, and leads only to the perpetuation of a vintage mistake in new directions. I encourage the task force to reconsider this topic accordingly. In the interim, I advise a discussion with your provider about what’s right for you, to find a personalized path through the prevailing muddle.