ScienceDaily (Aug. 29, 2000) — Older women with high estrogen levels are less likely to suffer cognitive decline, says a new study from researchers at the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center. While previous studies did not find such an association, the researchers explained that the new study measured estrogen that was free from other proteins, which is the form of the hormone most likely to affect the brain.

The new study supports the theory that taking estrogen after menopause may help some women avoid Alzheimer's disease, said Kristine Yaffe, MD, UCSF assistant professor of psychiatry, neurology and epidemiology, and chief of geriatric psychiatry at the San Francisco VA Medical Center. However, before deciding about hormone replacement therapy women should consider other factors, such as evidence that estrogen can reduce the risk of osteoporosis, and can increase the risk of breast cancer, she said.

Earlier research had shown that higher levels of estrogen in the blood might not protect against cognitive decline. But most of the estrogen molecules measured in these studies would have little effect on the brain, because 90 percent of all estrogen is bound to a protein that prevents it from getting past the protective barrier between the bloodstream and the brain. "Estrogen that is bound to protein is not as biologically active and cannot exert its effect whereas the loosely-bound and free forms can," Yaffe said.

The current study, published in the latest issue of the Lancet, used a relatively new test that measures free estrogen and estrogen that is loosely bound to proteins.

Yaffe and her colleagues studied 425 women over the age of 65 who are part of an ongoing study. They determined their natural levels of free or loosely bound estrogen by measuring levels of estradiol, a specific estrogen molecule. The researchers also gave the women a test to assess their memory, attention, language and calculation abilities at the beginning of the study, and again 6 years later.

Women in the study who had the highest free estrogen levels, had a 70 percent lower risk of cognitive decline compared with the women who had the lowest estrogen levels, Yaffe said.

"Estrogen looks like it really is protecting against cognitive decline," Yaffe said. It's likely that this decline is, in many cases, a precursor to Alzheimer's disease, although the study did not make that clinical assessment, she added.

If women with naturally low estrogen levels can be identified by testing, it is possible that they could take estrogen to help ward off cognitive decline, Yaffe said. She emphasized, however, that a clinical trial would be the best way to know whether estrogen could help.

"There are a number of ways in which estrogen may be protective in the brain," Yaffe said, including stimulation of brain cell growth, control of the chemicals that transmit messages in the brain, and protection from stroke damage.

Co-authors on the study included Steve Cummings, MD, UCSF professor of medicine and epidemiology, Li-Yung Lui, MA, MS, statistician in the department of epidemiology and biostatistics, Deborah Grady, MD, UCSF professor of epidemiology and biostatistics, Jane Cauley, DrPH, professor of epidemiology, School of Public Health, University of Pittsburgh, and Joel Kramer, PsyD, UCSF associate clinical professor of psychiatry.

This research was supported by grants from the National Institute on Aging.

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