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The Effects of Estrogen Therapy on Cognition

A large analysis of estrogen therapy in younger postmenopausal women, aged 50–55, found no long-term risk or benefit on cognitive function.

Hormone therapies are approved by the U.S. Food and Drug Administration (FDA) for certain uses in postmenopausal women, such as severe hot flashes. Because of health risks, such as a higher chance of stroke, FDA recommends it be used at the lowest doses for the shortest period needed.

Conjugated equine estrogens are the most common type of postmenopausal hormone therapy. A previous study, the Women’s Health Initiative Memory Study (WHIMS), found cognitive deficits and increased risk for dementia among women who had been prescribed this type of hormone therapy when they were ages 65 and older.

The Women’s Health Initiative Memory Study of Younger Women (WHIMSY), an extension of WHIMS, explored whether hormone therapy affects brain health when given to younger postmenopausal women. Researchers enrolled more than 1,300 women who started treatment when they were between 50 and 55 and continued for an average of 7 years. Over 1,100 of the women participated in a telephone assessment of cognition an average of 7 years afterward. The study was funded by NIH’s National Institute on Aging (NIA) and National Heart, Lung and Blood Institute (NHLBI).

The researchers assessed global cognitive function, which includes memory, problem-solving skills and other cognitive abilities. They also measured specific cognitive functions: verbal memory, attention, executive function, verbal fluency and working memory. The assessment was done when the participants’ average age was about 67 years and repeated a year later. Results appeared online in JAMA Internal Medicine on June 24, 2013.

The scientists found no meaningful difference in global cognitive function between women assigned to receive hormone therapy or placebo. There were no significant differences for any specific cognitive measures either.

“In contrast to findings in older postmenopausal women, this study tells women that taking these types of estrogen-based hormone therapies for a relatively short period of time in their early postmenopausal years may not put them at increased risk for cognitive decline over the long term,” says co-author Dr. Susan Resnick of NIA. “Further, it is important to note that we did not find any cognitive benefit after long-term follow-up.”

Why the effects of these hormone treatments on cognition differ by age is unknown. The scientists will continue to follow the participants to assess longer term effects. Because of the complicated effects of hormone therapy, women should consult their physicians about its use.