University of Vermont

University Communications

Investigating Estrogen's Other Side

Release Date: 03-11-2004

Author: Jennifer Nachbur
Phone: 802/656-7875 Fax: 802-656-3961

A few years ago, actress and model Lauren Hutton was singing the praises of hormone replacement therapy in a national advertising campaign. Since then, media coverage of estrogen has gotten uglier. But Professor Paul Newhouse thinks some form of the therapy might help cognition, and his National Institute on Aging-funded research is exploring estrogen's role in the brain.

Long-prescribed to treat menopausal symptoms such as hot flashes and night sweats, HRT was also believed to help prevent osteoporosis and heart disease. Then, in July 2002, alarm struck postmenopausal women worldwide when the National Institutes of Health put an early stop to the estrogen/progestin arm of the landmark Women's Health Initiative study due to evidence of the role of long-term HRT in increasing heart disease risk. More apparently negative findings have appeared since then, and just two weeks ago, the NIH halted the second half of the WHI when results showed the women involved were receiving no heart benefit and a slightly increased risk of stroke from taking estrogen alone.

According to some scientists, the two varieties of HRT tested in the WHI studies -- one combination estrogen/progestin and estrogen alone -- may not be the optimal or even appropriate hormone combination approach to use. The risks reported in these findings were sufficient to scare postmenopausal women, but neglected to answer one key question: Is HRT worth taking at all? Research is ongoing, but Newhouse, for one, sees hope on the horizon for the divisive therapy.

"Estrogen -- despite its currently controversial status right now -- appears to have a good side," says Newhouse, who is studying estrogen's role in the brain, specifically in regards to postmenopausal women's mood and memory systems, as well as its effect on Alzheimer's disease. "A large number of epidemiologic studies suggest that estrogen administration after menopause is helpful for preserving brain function. Estrogen may act on the cholinergic system of the human brain, which is believed to be critical for attention, learning, memory, and psychomotor performance."

Thinking estrogen
Newhouse, who is collaborating with, among others, Dr. Julia Johnson, professor of obstetrics and gynecology, is pursuing a three-tiered project funded by a five-year National Institute on Aging grant focused on the cognitive benefits of short-term estrogen use. In one study, participants receive either a single dose of estrogen or three months of estrogen and will undergo cognitive function testing to compare the effects. Another study compares the effects of estrogen plus progesterone, estrogen alone, and placebo on participants' cognitive function. And a third study examines how tamoxifen -- the "anti-estrogen" drug widely prescribed to breast cancer patients to prevent recurrence -- compares to placebo in its effects on cognitive function over a period of three months. Participation in the study will take nine months to one year per person.

Estrogen research is not a new area for Newhouse, or for his colleagues across the country. In 1999, a groundbreaking study at Yale using functional magnetic resonance imaging provided evidence that estrogen changed brain activation patterns in postmenopausal women that were performing memory tasks. Prior to receiving his NIA grant last fall, Newhouse conducted smaller-scale studies on estrogen's effects, in combination with other therapies, on cognitive function. One of his early study participants was 60-year-old Patty Levi of Burlington.

"My dad had Alzheimer's and my mother and sister had cancer, so I hadn't taken estrogen yet, but I had been curious about it," Levi says. During her study participation, Levi took computerized tests and verbal tests, which included making lists and retelling stories. "I didn't know whether I was getting estrogen or the placebo, but I did experience some relief of menopausal symptoms after taking the first pill," she says. She said she was not able to determine whether or not the hormones had an impact on her cognitive performance, but had more difficulty with the verbal tests.

Newhouse reports that almost daily, he receives scientific articles showing the positive effects of estrogen on brain function. "Because of the WHI, we now have confirmed evidence that long-term use of HRT is not a beneficial therapy for primary cardiovascular disease prevention, but there are still a lot of potential benefits to hormones that scientists haven't even scratched the surface on," he said. "We are really trying to understand the mechanisms -- what estrogen is doing to the brain -- and to better define how it can be beneficial for protecting cognitive function in postmenopausal women."

Study volunteers sought
Postmenopausal women age 50 and over who are non-smokers, not currently taking HRT or antidepressants, and have no history of breast cancer, are eligible to enroll in the studies, which include free physical and cognitive screening, free study medications, and reimbursement for time and travel expenses. For more information, contact Sally Ross-Nolan in the department of psychiatry at 847-9488.

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