Study to Clarify Safety, Effectiveness of Hormone Therapy During Menopause

When is the best time in a woman's reproductive history to start hormone therapy? How does estrogen therapy affect a woman's cognition and mood? What is the most beneficial form of estrogen?

These are just a few important questions that researchers at the University of Wisconsin School of Medicine and Public Health hope to answer in a federally funded nationwide study, the first of its kind, on the effects of estrogen therapy with perimenopausal women.

Led by Sanjay Asthana, head of the UW Section of Geriatrics and Gerontology and director of the Geriatric Research, Education and Clinical Center, the study will be the first in the world to address the most significant questions remaining about the use of hormone therapy in women.

The study, dubbed "KEEPS" (the Kronos Early Estrogen Prevention Study), will evaluate the efficacy of four years of hormone therapy on measures of cognition and mood in 720 healthy perimenopausal women at eight different sites across the country.

The main objective of KEEPS is to answer questions at the center of the hormone therapy debate. Originally, it was believed with certainty that the Women's Health Initiative (WHI) proved that women should not use estrogen because it causes breast cancer and has no benefits for cardiovascular disease. Today, researchers understand that the WHI was not designed to address younger women entering menopause.

"There has been a tremendous amount of important and valuable research done on the positive and negative health effects of therapy using estrogen in menopausal women," says Asthana. "It is my belief that this study will go a long way in helping us understand the complexity of estrogen and related hormones in humans. It is critical that we continue to systematically address all of the clinical issues concerning estrogen treatment and its effects on diseases like Alzheimer's."

Among the many objectives of KEEPS, is whether a natural, human form of estrogen, administered via an arm patch, has more benefit and less negative effect than the commonly used oral form of estrogen that is synthesized in the laboratory from animal sources. Researchers also hope to find that with younger women, the natural form of estrogen therapy can be administered for a much shorter period, with positive gains in cognition later in life.

The study also hopes to determine the best way to counteract the adverse effects of estrogen on the lining of the uterus, which hormone therapy regimen best mimics the menstrual cycle, and the relationship, if any, between estrogen-induced changes in markers of atherosclerosis, heart disease, inflammation, and blood hypercoagulability.

The $3.4 million study, funded by the National Institutes of Health (NIH), will be administered at the University of Wisconsin-Madison and the William S. Middleton Memorial Veterans' Hospital. Recruiting will take place at eight different sites across the United States.