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Stanford University School of Medicine

Does timing or composition of hormone therapy affect intellect? Meh.

8279076048_9133db5f9d_bThere are solid reasons for women reaching menopause to consider hormone therapy: notably, the relief of common, life-disrupting symptoms of early menopause such as hot flashes, night sweats and depression. But hormone therapy was once believed to do much more than that -- to wit, it was thought to lower the risks of everything from heart disease to intellectual decline.

Now, a carefully controlled large, long-term study led by Stanford neurologist and health-policy researcher Victor Henderson, MD, and published in Neurology has determined that hormone therapy using estradiol, the dominant natural sex steroid in women of childbearing age, has essentially no effect on the intellectual capabilities of women who begin the study mentally healthy, whether treatment begins soon after menopause or long afterward.

In a news release about the study, I wrote:

Hormone therapy was extremely popular in the United States in the latter part of the last century, but its use -- while still widespread, with users numbering in the millions -- has dropped off considerably since 2002, when findings from the Women's Health Initiative, a large-scale longitudinal study, raised deep doubts about many of what had been believed to be the treatment's broad benefits.

The new study, an extension of a trial at the University of Southern California called Early Versus Late Intervention with Estrogen, or ELITE, sought to determine whether starting hormone therapy soon after menopause, rather than many years later, can help retain mental abilities such as memory, reasoning, planning and selective attention. Some evidence suggests that for a woman to benefit from hormone replacement, it may be essential to start soon after menopause.

A second question: Might outcomes for women taking estradiol and progesterone, another steroid involved in the menstrual cycle, be different from those for women who took Prempro, which was used in the Women's Health Initiative? Prempro -- once the most widely-prescribed drug in the United States -- contains modified estrogens derived from mares' urine combined with medroxyprogesterone acetate, a substance whose effects overlap with but don't duplicate those of progesterone.

In Henderson's study, 567 postmenopausal women between the ages of 41 and 84 who showed no signs of dementia were divided into two groups -- those whose last menstrual period had been at least ten years earlier, and those reaching menopause within the last six years -- and put on regimens of either estradiol or a placebo. Women who hadn't undergone hysterectomies also received natural progesterone.

The women's verbal memory, overall neuropsychological condition and executive functions such as judgment, planning, reasoning and focusing attention were assessed at the beginning of the trial and at 2.5 years and five years later. The difference between the "early starter" and "late starter" groups on any of these measures was negligible. Nor was there appreciable difference in test performance between women receiving estradiol and those given a placebo, regardless of how soon after menopause the women began treatment.

"This study indicates that there's no particular reason to fear harmful effects on cognition over a five-year period of use," Henderson told me when I talked to him about the study. "But there's no reason to expect that this treatment, by itself, will result in meaningful improvement of mental abilities, either."

(The cardiovascular, as opposed to cognitive, benefits of starting hormone therapy early, I should mention, may be another story.)

Previously: Estradiol - but not Premarin - prevents neurodegeneration in women at heightened dementia risk, Hormone therapy halts accelerated biological aging seen in women with Alzheimer's genetic risk factor, Studying the link between post-menopausal hormones, cognition and mood and Hormone therapy soon after menopause onset may reduce Alzheimer's risk
Photo by Ron Kroetz

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