Estrogen Preserves Working Memory in Pre- but Not Postmenopausal Women

Caroline Cassels

October 16, 2006

October 16, 2006 (Chicago) – Estrogen may help preserve working memory in premenopausal women but may not have the same beneficial effect in postmenopausal individuals, 2 new studies suggest.

The studies, presented by the same group here at the American Neurological Association 131st Annual Meeting, examined the effects of ovarian steroid hormones on working memory and executive function in pre- and postmenopausal subjects.

"Our results suggest estrogen may be important for the maintenance of working memory and executive function before menopause but not necessarily after menopause," the studies' coinvestigator Miglena Grigorova, PhD, from the Ventana Clinical Research Corporation in Toronto, Ontario, told Medscape.

In the first cross-sectional study, the neuropsychological performance of 37 postmenopausal women age 65 years and older who used either estrogen only (22) or estrogen plus progesterone (15) continuously was compared with that of 28 age- and education-matched women who had never used hormone replacement therapy.

Subjects' mood, attention, verbal learning and memory, executive functions, and working memory were assessed through a comprehensive battery of tests.

No Difference in Older Women

The results showed no differences in executive function and working memory between the 3 groups.

"We were surprised by this, as we were expecting that the estrogen-only group would do better on working-memory tests and possibly even executive function, so we decided to conduct a second study to see whether estrogen had an effect on these domains before women reached menopause," said Dr. Grigorova.

The second study was a prospective design and included 25 premenopausal women with an average age of 36 who received leuprolide acetate depot (LAD), a gonadotropin-releasing hormone analog (GnRHa), for 4 weeks to suppress ovarian function and subsequent synthesis of estrogen and progesterone.

Subjects in this study had the same level of education and socioeconomic status as the elderly subjects in the first study. Furthermore, they were subjected to the same battery of tests as their older counterparts.

The women's baseline scores were compared with their posttreatment scores and with the scores of a control group of 25 naturally cycling women.

Significant Effect

"Following 4 weeks of treatment, we found executive functioning was not affected and did not differ pre- and posttreatment. However, working memory was negatively affected, and their performance on the 3 tests of working memory showed a significant decrease that was clinically evident to the point that the women noticed the difference themselves," said Dr. Grigorova.

At this point, the study indicates that giving estrogen to postmenopausal women may not help their working memory but may be of benefit to younger women who have had surgical removal of their ovaries.

Furthermore, she added, it is important for physicians to be aware of the potential long-term effects of on their patients' working memory when prescribing GnRH agonist therapy.

She added that further research is needed to determine whether the results of the first study in postmenopausal women can be replicated using transdermal estrogen therapy. "About 75% of the [postmenopausal] women in our study were taking oral estrogen. There have been some reports that oral estrogen does not have the same positive effect as transdermal estrogen on cognition, and therefore this needs to be tested," she said.

ANA 131st Annual Meeting: Abstract M-95.

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