By MICHELLE L. BRANDT

Poor estrogen. Its name keeps getting dragged through the mud. Just weeks ago the National Institutes of Health announced estrogen treatment may increase risk of stroke among postmenopausal women. A related study from 2002 linked a therapy combining estrogen and progestin with increased risks of breast cancer, heart attack and stroke.

Despite the news, Natalie Rasgon, MD, PhD, associate professor of psychiatry and behavioral sciences at the School of Medicine, doesn't think estrogen should be written off.

Referencing past studies that point to the cognitive benefit of the hormone, Rasgon is launching an NIH-supported study that explores estrogen in postmenopausal women at risk for cognitive decline.

“The pendulum has swung very far on hormone replacement therapy. Ten years ago, everyone said ‘hooray' to it; now some women are afraid,” said Rasgon. “The notion of people telling women to go off estrogen is distressing. Some women feel they can't live without it. And we can't ignore basic science and observational studies that showed estrogen's neurotrophic benefit.”

Rasgon noted biological evidence showing that estrogen plays a role in cognitive function, and past studies have pointed to possible protective benefits of the hormone. In a 2001 study, published in the American Journal of Psychiatry, postmenopausal women on estrogen replacement therapy possessed better learning and verbal memory than did women who had never taken estrogen. Observational studies also have suggested that estrogen may decrease a woman's likelihood of developing Alzheimer's disease.

One NIH study -- the Women's Health Initiative Memory Study, or WHIMS -- recently showed that taking a combination of estrogen and progestin actually increased the risk of dementia in women.

However, this study focused on older women who had not received hormone therapy in the past, and Rasgon said the results might be applicable only to this specific group of women. (The average age of the study's participants was 71.)

A concept called “window of opportunity” also suggests there is a time -- probably at the start of menopause -- when estrogen replacement therapy might be most helpful to the brain. For that reason, Rasgon said, the results of the WHIMS study cannot be extrapolated to younger women or those who started therapy around the time of menopause.

“To make a sweeping statement that estrogen use is associated with cognitive decline is erroneous -- and it's unfair to the women who take estrogen,” said Rasgon, who also directs Stanford's Behavioral Endocrinology Program, which focuses on the relationships between mood, brain function and hormones.

Rasgon's study aims to explore the main effect of estrogen in the aging brain and to define a middle ground on the estrogen issue. The postmenopausal women in her study will be on estrogen replacement therapy when they enroll in the study; during the trial they will be randomized to either continue or discontinue hormone use. Rasgon and her team will perform a comprehensive assessment of brain function -- including a neurological examination, neuropsychological testing and brain imaging such as PET and MRI studies -- at the beginning of the trial and then after a two-year period.

Rasgon said the novelty of her five-year study is its design. Her team will investigate women who are stopping hormone therapy and compare them with women who continue to take estrogen. “The big question is, ‘Will women who stop experience a decline in their cognitive function?' ” she said. “Unlike in the WHIMS study, we'll use imaging to actually see the changes in brain functioning.”

Participants in the study must be age 50 to 65, currently using estrogen replacement therapy and have risk factors for dementia, which include family history of dementia, major depression and hypothyroidism. People interested in volunteering or learning more about other Behavioral Endocrinology Program studies, can call 724-9269.