In the U.S., the average age of menopause is 51, and it's a time when many women first begin to experience lapses of memory. Now, a Stanford University School of Medicine study shows that decreased estrogen levels after menopause are unrelated to changes in mood and cognitive ability. Yet, among younger postmenopausal participants in the study, the researchers discovered a possible link between levels of another sex hormone — progesterone — and some cognitive competencies. The study appears in the Proceedings of the National Academy of Sciences.

Hormones and Hormone Therapy

Estrogens, the primary female sex hormones, are a group of steroid compounds produced primarily by the ovaries. These hormones, which include estriol, estradiol, and estrone, are responsible for women’s female characteristics and sexual functioning, as well as bone health and some brain functions. Estrogen levels fall during menopause, when women begin to experience a permanent reduction in their estradiol levels (the predominant estrogen during reproductive years), estrone, and progesterone, a hormone involved in the menstrual cycle.

Previously, many doctors would readily prescribe hormone treatments — medications containing replacement female hormones — for women suffering hot flashes and other symptoms of menopause. Hormone therapy, though, soon became controversial due to anecdotal, as well as scientific reports, of possible negative health effects. For instance, some studies found the timing of estrogen hormone therapy to be crucial; initiation of hormone therapy during midlife appeared to protect against cognitive impairment, but when hormone therapy was initiated later, it increased the risk of dementia.

Based on this "critical-window" theory and the fact that animal studies also proved the timing of estradiol replacement could affect memory, Victor Henderson, MD, and his colleagues at Stanford hypothesized that younger post-menopausal women with higher levels of estradiol would demonstrate better memory skills, while older post-menopausal women with higher levels of estradiol would not.

Data Analysis

For their study, Henderson and his team analyzed data on 643 healthy postmenopausal women, none of whom were on hormone therapy. The women ranged in age from 41 to 84. The researchers sorted the women into two categories: those who had gone into menopause less than six years previously, and those who had gone into menopause more than 10 years previously. Next, the researchers gave the women a series of neuropsychological tests to gauge their memory and overall cognition. Finally, the researchers assessed the women for symptoms of depression and measured their levels of estradiol, estrone, progesterone, and testosterone.

“We viewed the availability of hormone levels as an opportunity to test one aspect of the critical-window hypothesis," Henderson stated in a press release. "We found no significant link — positive or negative — in either group." Henderson noted that these findings don't "necessarily mean that estrogens are irrelevant to cognition, since we have no way of measuring estrogen directly at the brain level. But they imply that boosting blood levels of estradiol or estrone — even in younger postmenopausal women — may not have a substantial effect on cognitive skills one way or the other."

The researchers found all other hormone levels were unrelated to verbal memory, overall cognition, and mood, with a single exception: Higher progesterone levels in younger postmenopausal women appeared to be related to better memory and overall cognition. Although Henderson noted his team's findings have not previously been reported and need to be confirmed, he believes the work helps to clarify the role of hormones in age-related brain disturbances. Certainly the many women who value their cognitive abilities, whether pre- or post-menopause, appreciate continuing research in the area of hormonal effects on brain function.

Source: Henderson V, Mack W, et al. Proceedings of the National Academy of Sciences. 2013.