Although millions of women use hormone therapy, those who try it in hopes of maintaining sharp memory and preventing the fuzzy thinking sometimes associated with menopause may be disappointed. A new study indicates that taking estrogen does not significantly affect verbal memory and other mental skills. “There is no change in cognitive abilities associated with estrogen therapy for postmenopausal women, regardless of their age,” says Victor Henderson, a neurologist at Stanford University and the study’s lead author.

Evidence of positive and negative effects of such hormone therapy has ping-ponged over the years, with some observational studies in postmenopausal women and research in animal models, suggesting it improves cognitive function and memory. But other previous research, including a long-term National Institutes of Health Women’s Health Initiative memory study published in 2004, has suggested that taking estrogen increases the risk of cognitive impairment and dementia in women over 65 years old.

Henderson says one explanation for these contradictory findings may be that after menopause begins there is a “critical period” in which hormone therapy could still benefit relatively young women—if they start early enough. So in their study, which appears in the July 20 online Neurology, Henderson and his team recruited 567 healthy women, between ages 41 and 84, to examine how estrogen affected one group whose members were within six years of their last menstrual period and another whose members had started menopause at least 10 years earlier.

Women in each group were randomly assigned to daily oral regimens of either estradiol—the main type of estrogen produced by women in their reproductive years—or a placebo. The women who had not undergone hysterectomies were also given either progesterone vaginal gel or a placebo. In these women progesterone helped make the lining of the uterus thinner, mimicking the monthly bleeding of a menstrual cycle. Without progesterone, the lining is no longer shed and estrogen can cause an overgrowth of cells in the uterus, which can lead to cancer.

Subjects received the hormones or placebos for an average of five years. Investigators tested the participants’ cognitive skills at the beginning of the treatment, after 2.5 years and then again after five years. Both groups improved in verbal memory tests—but some improvement had been expected because the subjects had gained practice taking the tests, Henderson says. What was surprising was that there was no sign of significant benefit—or harm—in taking the hormone therapy, no matter how soon after menopause the women had begun. “Our results suggest that there’s no reason for healthy women to consider taking hormone therapy to improve memory, regardless of their age,” Henderson says. “On the other hand, if women are considering taking hormone therapy for approved indications such as treatment of moderate-to-severe hot flashes and night sweats or for osteoporosis prevention, then they don’t need to be overly concerned about negative effects of estrogen on memory.”

The results could offer reassurance to postmenopausal women, says Carey Gleason, a geriatrics and women’s health specialist at the University of Wisconsin–Madison, who was not involved in the study. Most women take hormone therapy for hot flashes, which can disrupt sleep and affect overall quality of life, she says, and nearly 80 percent of menopausal women have severe hot flashes. But the long-term effects of estrogen therapy are still unclear, Gleason says. “It's important to recognize that dementia, and especially Alzheimer's disease, take decades to actually bloom. So following up on the effects of estrogen in these women 10 to 15 years later should be the next step that researchers focus on.”