Women's Natural Estrogen Levels Help Protect Against Cognitive Decline, UCSF/VA Study Says

The new study supports the theory that taking estrogen after menopause may helpsome women avoid Alzheimer's disease, said Kristine Yaffe, MD, UCSF assistantprofessor of psychiatry, neurology and epidemiology, and chief of geriatricpsychiatry at the San Francisco VA Medical Center. However, before decidingabout hormone replacement therapy women should consider other factors, such asevidence that estrogen can reduce the risk of osteoporosis, and can increasethe risk of breast cancer, she said.

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

The current study, published in the latest issue of the Lancet, used arelatively new test that measures free estrogen and estrogen that is looselybound to proteins.

Yaffe and her colleagues studied 425 women over the age of 65 who are part ofan ongoing study. They determined their natural levels of free or looselybound 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 6years later.

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

"Estrogen looks like it really is protecting against cognitive decline," Yaffesaid. It's likely that this decline is, in many cases, a precursor toAlzheimer'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 ispossible that they could take estrogen to help ward off cognitive decline,Yaffe said. She emphasized, however, that a clinical trial would be the bestway 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 thechemicals that transmit messages in the brain, and protection from strokedamage.

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

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