Ob/Gyn panel revisits HRT - HealthLINK (Women)

The pendulum edges back on hormone replacement

Many women remain confused in the aftermath of the Women's Health Initiative study about the safety and benefits of taking hormone replacement therapy. The coverage of that study's results led to a lot of misunderstanding, and this ACOG report addresses some of the key issues that will hopefully help women and their physicians make appropriate decisions about its use. The ACOG guidelines introduce some balance into the risks vs. benefits equation.

“The ACOG guidelines introduce some balance into the risks vs. benefits equation.”

Years ago, many physicians observed how effective HRT was in relieving menopausal symptoms, and we began to think of it as somewhat of a panacea for a variety of ills related to aging. The pendulum swung way over to one side. The WHI study with its cautionary tale about health risks and its questioning of preventive benefits made everyone step back, and the pendulum swung to the opposite extreme.

One of the results was that more than half of the women who were taking it to relieve menopausal symptoms stopped. Many of these women were forced to again cope with sweats, insomnia, depression and other negative health issues.

WHI study population skewed results
Now the pendulum is beginning to slide back to somewhere in between the two extremes. The fact is the WHI study, which was a technically rigorous large prospective study, was skewed. The average age of participants at the beginning of the study was 63, more than a decade older than the average age of women entering menopause. At the end of the study, some of these women were in their 80s, a very high-risk population for some of the health conditions documented such as heart disease, stroke and breast cancer.

Cardiac benefits if HRT is started early
Animal studies have shown us that the protective cardiovascular benefits of HRT only come into play if hormones are taken early—at the onset of menopause. The HERS trial showed us that giving HRT to women who already had heart disease didn't work. We believe, and there's evidence to substantiate our belief, that if women take HRT when beginning menopause, they will experience less atherosclerosis.

Older women past the menopausal transition who begin HRT are past the window of opportunity where HRT can provide that benefit. Yale is currently one of 10 centers participating in the Kronos Early Estrogen Prevention (KEEP) Study, which is examining the cardiovascular effects of estrogen on women ages 40 to 55 who recently have entered menopause. That study should help us answer this question.

Other HRT benefits
The ACOG report also confirms the antidepressive benefits of estrogen. We don't know whether this effect is a direct result of estrogen or a byproduct of relieving menopausal symptoms that can interfere with sleep and result in anxiety and depressed mood.

The same is true of sexual desire. There is evidence that estrogen helps in this area, but we're not sure if it's a direct effect or a result of improved sleep, mood and relief of vaginal atrophy and dryness.

What about the risks?
The number of women in the WHI study who were diagnosed with heart disease, breast cancer, stroke and other diseases was very small, less than one in 1,000. It's true that the percentage increase in these diseases did rise, but the risk is very small. Few drugs have been studied as thoroughly as Prempro and Premarin, and the good news is we know the risks with these medications so we can help our patients make informed decisions about taking them.

“The negative publicity that resulted about HRT from the WHI study has done women a disservice.”

The fact is that even with the very senior women in the WHI study, the risks were very small. In fact, when we look at the overall mortality rates in the WHI study and compare the HRT and placebo groups, the risk of death from all causes was ever-so-slightly lower in the HRT group.

HRT now prescribed differently
The WHI study did result in our practice of prescribing the lowest effective dose of estrogen to relieve symptoms, and that seems to make good sense. There are now very low-dose preparations available so women can try various doses and determine which dose works for them. All in all, however, my opinion is that the negative publicity that resulted about HRT from the WHI study has done women a disservice.

Ongoing trials may well show us that early administration of HRT may provide significant ongoing benefits—including a lower risk of Alzheimer's, heart disease and osteoporosis—that women who never started or who stopped taking it may never experience.

Who should not take the drug? Any woman with an estrogen-sensitive cancer should not take HRT, along with women with undiagnosed vaginal bleeding.

The ACOG report has helped put this issue in perspective, but I think it did not go far enough. The pendulum shouldn't swing back to where it was, but I think it could go farther than this report indicates.

Dr. Taylor is an associate professor of reproductive endocrinology and infertility at the Yale University School of Medicine and an attending obstetrician/gynecologist at Yale-New Haven Hospital.

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