Objective: Women who undergo both natural and surgical menopause experience the loss of cyclic ovarian production of estrogen, but hormonal and demographic differences distinguish these two groups of women. Our objective was to review published evidence on whether the premature cessation of endogenous estrogen production in women who underwent a surgical menopause has deleterious consequences for cognitive aging and to determine whether consequences differ for women if they undergo natural menopause. Studies of estrogen-containing hormone therapy are relevant to this issue.
Design: We reviewed evidence-based research, including the systematic identification of randomized clinical trials of hormone therapy with cognitive outcomes that included an objective measure of episodic memory.
Results: As inferred from very small, short-term, randomized, controlled trials of high-dose estrogen treatment, surgical menopause may be accompanied by cognitive impairment that primarily affects verbal episodic memory. Observational evidence suggests that the natural menopausal transition is not accompanied by substantial changes in cognitive abilities. For initiation of hormone therapy during perimenopause or early postmenopause when the ovaries are intact, limited clinical trial data provide no consistent evidence of short-term benefit or harm. There is stronger clinical trial evidence that initiation of hormone therapy in late postmenopause does not benefit episodic memory or other cognitive skills.
Conclusions: Further research is needed on the long-term cognitive consequences of surgical menopause and long-term cognitive consequences of hormone therapy initiated near the time of surgical or natural menopause. A potential short-term cognitive benefit might be weighed when a premenopausal woman considers initiation of estrogen therapy at the time of, or soon after, hysterectomy and oophorectomy for benign conditions, although data are still quite limited and estrogen is not approved for this indication. Older postmenopausal women should not initiate hormone therapy to improve or maintain cognitive skills.
A review of research on surgical and natural menopause, including the systematic review of randomized clinical trials of hormone therapy, provides limited evidence that surgical menopause may be accompanied by a decline in verbal episodic memory, that the natural menopause transition is not accompanied by substantial changes in cognitive abilities, and that hormone therapy during perimenopause or early postmenopause has no substantial short-term effect on cognitive skills when ovaries are intact. There is good evidence that hormone therapy initiated in late postmenopause does not substantially affect episodic memory or other cognitive skills.
From the 1Department of Health Research and Policy (Epidemiology) and Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA; and 2Department of Psychology and Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada.
Received October 3, 2006; revised and accepted January 19, 2007.
Financial disclosure: Dr. Henderson has consulted for the Council on Hormone Education and Wyeth, and he receives research support from the National Institutes of Health.
Address correspondence to: Victor W. Henderson, MD, MS, Stanford University, 259 Campus Drive, mc 5405, Stanford, CA 94305-5405. E-mail: firstname.lastname@example.org.