Hormone Replacement's "AHAH" Moment

It has long been clear that effects of hormone replacement are best when treatment begins early rather than late after menopause. The data showed such distinctions, but they too were obscured by a rush to summary judgment.
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I was privileged to attend a recent continuing education conference about estrogen replacement at menopause, held at the Yale School of Medicine, organized by my friend and colleague, Dr. Phil Sarrel. Highlights for me included both Dr. Sarrel's important insights, and a very poignant, personal story told by Michelle King Robson, founder of EmpowHER. Michelle had what eventually proved to be diverticulitis. Initially misdiagnosed, her condition was erroneously treated with a hysterectomy. Michelle's overall health plummeted due to a surgically induced menopause, until it was restored with judicious hormone replacement.

The conference was a culminating event in a months-long effort, again led by Dr. Sarrel, to provide the field of hormone replacement a much-needed "aha" moment. Having served for 8 years as Oprah's nutrition columnist in O Magazine, that certainly resonates with me. In this case, however, the revelation comes in the form of an "AHAH" moment, standing for: advancing health after hysterectomy. We will return to that shortly. For now, here is the back story.

Roughly two years ago, Dr. Sarrel brought to my attention a research study published in JAMA looking at long term health effects in women who did, or did not, receive estrogen replacement after hysterectomy. This sample of women was a subgroup of the larger population enrolled into the well-known Women's Health Initiative, or WHI.

That large trial, funded by the NIH, is largely responsible for reversing the prevailing attitude about hormone replacement at menopause. Observational studies had suggested decreased chronic disease and premature death risk with hormone replacement. As a result, hormone replacement at menopause became rather routine in the service of preventing serious chronic disease, heart disease in particular, for a span of years.

The WHI, the largest of several randomized intervention trials to examine the issue, essentially said: au contraire. The report of no net health benefit, and some net harm, from hormone replacement produced a fairly abrupt and complete about face in public attitude and clinical practice alike. Hormone replacement was suddenly yesterday's bad news.

But as so often happens at the interface of medicine and the media, important nuance was lost. For one thing, the WHI, like the other randomized trials, only studied one variety of hormone replacement, called Prempro. Though popular, Prempro is not considered anything close to optimal hormone replacement by those expert in the field. The attribution of harms from Prempro to all varieties of hormone replacement was an important nuance, lost in the customary oversimplifications and hyperbole of media.

For another, the results of hormone replacement vary widely with timing. It has long been clear that effects of hormone replacement are best when treatment begins early rather than late after menopause. The data showed such distinctions, but they too were obscured by a rush to summary judgment.

For yet another, the net harms of even Prempro in even a mixed population of women starting hormone therapy both early and late after menopause were very sparse. The WHI data actually showed both benefits and harms, and they were pretty closely matched. Headlines shouting out warnings about net harms made hormone replacement sound far worse than objective data ever suggested; the data showed something pretty close to a toss-up.

Finally, and most importantly, the data showed very different effects in women who, because they had undergone a hysterectomy and did not need to take progesterone, could take estrogen only. What Dr. Sarrel pointed out to me those two years ago were published data indicating 13 fewer deaths per year per 10,000 women in their 50s treated with estrogen, rather than placebo. Estrogen alone, used in relatively young women right after menopause, was saving lives.

Provided this crucial observation, my job was to translate the study data into real-world effect. Colleagues and I, working with Dr. Sarrel, did just that, and published our findings in the American Journal of Public Health. Our analysis suggested that over a decade, over-zealous avoidance of estrogen replacement had resulted in tens of thousands of premature deaths among women in the U.S. alone.

It would be hard to overstate the sense of urgency that ensued when we looked at such stark and alarming data. The result of that consternation, and passion, is AHAH, a campaign, and a non-profit organization, devoted to clarifying to women, and their physicians, the nuanced realities of hormone replacement. There are different kinds of hormones; different kinds of women; and different effects as a result. Estrogen therapy in younger women who have undergone hysterectomy saves lives, mostly by preventing heart attacks.

The Yale conference was an example of the kind of education and outreach to which AHAH is committed. An "aha moment" is great, but moments come and go. It takes a campaign, and time, to change hearts and minds.

Hormone replacement is not right for all women, but nor is it wrong; we have now bungled this in both directions, and failed to distinguish baby from bathwater. Dr. Sarrel is an impassioned, indefatigable champion of the nuanced understanding necessary to optimize hormone replacement, and save lives. By taking AHAH from a mere moment to an on-going campaign, I believe he can help us all get it right this time.

-fin

Director, Yale University Prevention Research Center; Griffin Hospital

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