Hormone replacement doesn’t appear to dull memory, may improve mood

A major new study of women at midlife has found that those who received hormone-replacement therapy soon after entering menopause did not experience declines in memory or other measures of cognitive health. And menopausal women who followed an oral estrogen-plus-progesterone regimen were less prone to depression and had better mood.

Those findings emerged Tuesday from an extension of the Kronos Early Estrogen Prevention Study, or KEEPS, designed to gauge the cognitive impact of hormone replacement therapy. Although the influential Women’s Health Study had linked hormone therapy to cognitive decline in women 65 and older, the KEEPS researchers wondered whether a shorter and earlier stint on hormone replacement would also put a woman at increased risk for memory and other mental problems.

After tracking 662 participants for an average of nearly three years, the KEEPS trial found that for women who enrolled in the trial around age 50, neither oral estrogens-plus-progesterone nor an estradiol patch-plus-progesterones degraded performance on tests of short- and long-term memory, verbal fluency and reasoning skills.

Over time, however, women who were assigned to get oral estrogens and progesterone reported moods that were less anxious, tense, depressed and dejected than those reported by women who were on placebo medications or who received the estradiol patch-plus-progesterone.

The findings were published Tuesday in the journal PLOS Medicine.

The study’s findings are in keeping with growing evidence that, for women who take hormone replacements close to the time of their last period, and who stay on it for just a few years rather than decades, easing the symptoms of menopause may not be so dangerous.

The landmark Women’s Health Initiative, which focused on women older than 65 and found higher rates of breast cancer, strokes and cognitive troubles in those taking hormone replacement, dramatically drove down the numbers of women who underwent such therapy. As research has found that earlier and briefer hormone replacement comes with much smaller risks -- and in some cases none at all -- more women have opted for the therapy.

For postmenopausal women who have not undergone hysterectomy, the addition of progesterone to the hormonal mix may also be important in reducing risks. The KEEPS trial supplemented its estrogen and estradiol with “cyclic” progesterone (a 200-milligram capsule of progesterone for 12 days each month rather than continuous administration).

“This study adds to our understanding of the risks and benefits of menopausal hormone therapy,” says Dr. Carey Gleason, assistant professor of medicine at the University of Wisconsin’s School of Medicine and Public Health. “For example, the findings could mitigate concerns about cognitive harm for women who opt to use hormone therapy” to treat such symptoms as hot flashes and night sweats during menopause, she added.

But the authors of the latest research underscore that their reassuring findings apply only to fiftysomething women at the time they are on a hormone replacement regimen. Only lengthier tracking of women who took hormones will tell if they confer added risk or protection against cognitive decline more than a decade later. Until that is done, the longer-term cognitive effects of briefer-and-earlier hormone replacement therapy is still very much an open question.

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