Women's natural estrogen levels help protect against cognitive decline, UCSF/VA study says

By Leslie Harris

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

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.