Hormone Therapy: Sooner, Later, or Not at All?

Sorting out the cloudy issue that is estrogen replacement

By Robert W Lash MDJun 11, 2007 5:00 AM


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In thebeginning, we thought estrogen was good for women. After all, when estrogentherapy was first studied, investigators thought they were seeing less heartdisease and Alzheimer’s among the women who took estrogen.

Why? Because when researchers looked at women who did and didn’t have heart disease or Alzheimer’s,and asked these women to recall their hormone use, those without these problemswere more likely to have taken estrogen. Thus hormone replacement therapy (HRT)was deemed a good thing. However, as time went on, the disadvantages of these"looking backwards" studies became more obvious: A woman who took HRTto stay healthy might also be more likely to eat right, exercise, and notsmoke.

Thisconcern (among others) gave rise to the Women’s Health Initiative (WHI), themost comprehensive "forward-looking" study of HRT. The WHI followedtwo groups of postmenopausal women, randomly giving half of the group HRT andthe other half placebo. The results showed a slight increase in heart diseaseand possibly a slight increase in Alzheimer’s in the group taking HRT. But manypro-estrogen physicians were unconvinced by the negative WHI results, andthey’ve been reanalyzing the data. One approach they’ve taken is to study thosewomen who entered the WHI just as they were starting menopause, rather thanlook at the entire WHI group, which included much older women. Some of theseanalyses suggest women who start HRT earlier do better than those who start itlater.

In a new study with a slightly differenttwist—the WHI Memory Study—investigators again looked at women in the WHI. Thistime they asked if they could relate the development of Alzheimer’s disease toestrogen use beforethe womenenteredthe WHI. The results suggest that early estrogen may protect againstAlzheimer’s, however this study needs to be taken in context.

First, allthe news reports for this study are based on a short presentation at a nationalmeeting, accompanied by only a brief written description of the study. Until itis published in a peer-reviewed journal, we won’t be able to fully evaluate themethods or the data. This is not a criticism, it’s just part of the scientificprocess. Exciting results get talked about at national meetings and generate quickmedia attention, but the full story comes out a few months later. Second, theinvestigators relied on women’s recollectionof their estrogen use. These recall studies are tricky, even for the mostcareful investigators, since self-reporting is often inaccurate. And it wasthis concern, in part, that led to the WHI in the first place. I’m not sayingthat these concerns invalidate the results of this study. Instead, I’m urgingcaution before embracing the results of any "study of the month."

So, doesestrogen prevent Alzheimer’s? Maybe. Does it matter when you take estrogen? Noone is really clear on that either. What we do know is that the differenceamong those taking estrogen and those abstaining isn’t large. My own feeling: Ifpreventing Alzheimer’s is the only reason you’re taking estrogen, you probablyshouldn’t bother. I suspect you’d be better off taking a daily walk and doingSudoku.

Robert W. Lash, M.D. is anassociate professor of internal medicine at the University of MichiganMedical School

and writes the Health Trends column for His clinical interests include thyroid disease,diabetes, endocrine disorders in pregnancy, osteoporosis and metabolicbone disease, and medical education.

Every month Dr. Lash answers questions from Discover readers, so if you're confused about health information, email him at

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