Estrogen Deficit No Good for Brain

Women who have had their ovaries removed and not received extra estrogen have an elevated risk of cognitive impairment or dementia later in life. The finding contrasts with an earlier study of about 7500 older women, which found an increased risk of dementia in women over 65 who took hormone supplements--suggesting that estrogen has a different effect on the brain at different ages.

Estrogen's effect on health and brain function has been hotly debated in recent years. In 2004, researchers with the Women's Health Initiative (WHI), who studied hormone replacement therapy after menopause, reported that women age 65 to 79 had an increased risk of dementia if they were taking hormone supplements containing estrogen (ScienceNOW, 27 May 2003). But the study, along with others from WHI that reported harm from hormone therapy, was criticized for its focus on older women. Many scientists wondered whether estrogen supplements would have the same hazardous effects in premenopausal women.

A team lead by neurologist Walter Rocca of the Mayo Clinic College of Medicine in Rochester, Minnesota, focused on women who had one or both ovaries removed. They used medical records to identify all those who fit this description in Olmsted County, Minnesota, who had had one or both ovaries removed between 1950 and 1987, because of a medical condition or to protect against cancer. They interviewed 1489 women who fit this description, and 10%, they found, had developed dementia. In a control group of 1472 women who had intact ovaries, the number was 6.6%. The findings suggest that it’s harmful to have too little estrogen before menopause, and make a strong case for estrogen treatment if ovaries are removed before age 50, say the researchers. The study is published in the 29 August online issue of Neurology.

The results jibe with other work, which examined how monkeys' brains benefited from the hormone when their ovaries had been removed just prior to menopause. "When we looked at the prefrontal cortex, the neurons had been restored to a youthful state, and this strongly supports this new research," comments neurobiologist John Morrison at the Mount Sinai School of Medicine in New York.

Still a mystery is how the hormone affects cognition in women most in need of supplemental estrogen--those in their 50s who are enduring the symptoms of menopause that estrogen can relieve. "Where and when estrogen switches from being protective to harmful is the next big question," Rocca says.

A WHI investigator still wonders precisely how estrogen affects the brain in younger women. "A randomized clinical trial may be necessary" to confirm the results of Rocca's study, says biostatistician Mark Espeland of Wake Forest University in Winston-Salem, North Carolina. But he agrees that the paper fits with earlier observational studies showing women who had their ovaries removed at a young age were at increased risk of cognitive decline.

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