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Hormone replacement therapy may improve mental function for some postmenopausal women

Hormone replacement therapy (HRT) improves some areas of mental functioning in women who have menopausal symptoms but has no clear cognitive benefits for asymptomatic women, according to a systematic review of the evidence that was supported in part by the Agency for Healthcare Research and Quality (contract 290-97-0018). The review is part of a comprehensive update on the benefits and risks of HRT being prepared for the U.S. Preventive Services Task Force. The review of studies from 1966 to 2000 included different types and dosages of estrogen with and without progestin.

In women with menopausal symptoms, HRT improved certain areas of cognition in particular, such as verbal memory (ability to recall lists of words, word pairs, or paragraphs), vigilance (ability to sustain attention), reasoning, and motor speed (for example, clerical speed or simple reaction time). In asymptomatic women, HRT did not have any consistent effects on results of formal tests of cognitive function. Although nonexperimental studies suggest a reduced risk of dementia among women who take HRT, methodologic problems in most of these studies prevent drawing strong conclusions about the effects of HRT on dementia.

Such neural and cognitive specificity is not surprising because estrogen receptors are not distributed uniformly throughout the brain, according to the researchers at the Oregon Health Sciences University Evidence-based Practice Center. They reviewed results of 17 studies on the effects of HRT on cognitive decline. Estrogen doses and formulations and duration of use varied.

Asymptomatic postmenopausal women showed no improvement in cognition. However, women suffering from symptoms typical of menopause such as fatigue, depression, sleep difficulty, and hot flashes, improved their verbal memory, vigilance, reasoning, and motor speed, perhaps because the HRT helped them sleep better, improved their mood, and reduced the number of hot flashes they experienced.

A meta-analysis of 12 observational studies suggested that HRT was associated with a 34 percent decreased risk of Alzheimer disease. However, these studies had several methodologic weaknesses—women taking HRT differed in other ways that may have lowered their risk of dementia, data on HRT use may have been inaccurate, and negative studies may have been less likely to be published. Overall, the studies did not contain enough information to adequately assess the effects of progestin use, various estrogen preparations or doses, and duration of therapy. The researchers suggest that future studies target specific cognitive effects of HRT, including it's ability to prevent Alzheimer disease. Two large prevention trials are underway that may provide more definitive answers to these questions.

See "Hormone replacement therapy and cognition: Systematic review and meta-analysis," by Erin S. LeBlanc, M.D., M.P.H., Jeri Janowsky, Ph.D., Benjamin K.S. Chan, M.S., and Heidi D. Nelson, M.D., M.P.H., in the March 21, 2001 Journal of the American Medical Association 285(11), pp. 1489-1499.

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