Does Estradiol Improve Memory in Postmenopausal Women?

Estradiol does not affect memory and other mental abilities differently in postmenopausal women near to menopause than it does in postmenopausal women further from the time of menopause, according to a new study.

“There is no overall cognitive benefit or cognitive harm in either group,” said lead study author Victor W. Henderson, MD, MS, of the departments of health research and policy (epidemiology) and neurology and neurological sciences at Stanford University. “We were disappointed that we were unable to demonstrate memory benefit in the early group of younger postmenopausal women.”
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In this double-blind trial, the researchers randomly assigned healthy women within 6 years of menopause or 10-plus years after menopause to oral 17β-estradiol, 1 mg/d, or to placebo. Women with a uterus received cyclic micronized progesterone vaginal gel or placebo. The primary outcome assessed at 2.5 and 5 years, compared between treatment groups, was change in a standardized composite of neuropsychological test scores assessing verbal episodic memory. Secondary outcomes assessed executive functions and global cognition.

The investigators included 567 women in modified intention-to-treat analyses after a mean treatment duration of 57 months. For verbal memory, the mean estradiol minus placebo standardized difference in composite scores (-0.06; 95% confidence interval [CI], -0.22 to 0.09) was not significant (2-tailed, P=.33). They found differences to be similar in early and late postmenopausal groups (2-tailed interaction P=.88). Interactions between postmenopausal groups and differences between treatment groups were not significant for executive functions or global cognition.

Estradiol initiated within 6 years of menopause does not affect verbal memory, executive functions, or global cognition differently than therapy begun 10-plus years after menopause, they concluded.

“The two main takeaway messages are: First, postmenopausal women of any age should not take hormone therapy to improve memory,” Henderson said. “Second, postmenopausal women considering hormone therapy for other indications—for example, to alleviate moderate-to-severe hot flash symptoms—should not be concerned that hormone therapy will have a harmful effect on memory for up to 5 years of use.”

—Mike Bederka

Reference:

Henderson VW, St. John JA, Hodis HN, et al. Cognitive effects of estradiol after menopause: a randomized trial of the timing hypothesis [published online July 20, 2016]. Neurology. doi:10.1212/WNL.0000000000002980.