8 National Centers Begin Recruitment for the Kronos Early Estrogen Prevention Study.

PHOENIX -- Eight national study centers are now recruiting for the Kronos Early Estrogen Prevention Study (KEEPS), which is being coordinated by Phoenix-based Kronos Longevity Research Institute (KLRI). The study focuses on the effects of hormone therapy (HT) as it relates to the progression of atherosclerosis (hardening of the arteries) in recently menopausal women. Participating centers include:

--Albert Einstein College of Medicine/Montefiore Medical Center (New York City)

--Columbia University College of Physicians and Surgeons (New York City)

--Harvard Medical School/Brigham and Women's Hospital (Boston)

--Mayo Clinic (Rochester, MN)

--University of California, San Francisco Medical Center

--University of Utah School of Medicine (Salt Lake City)

--University of Washington School of Medicine/VA Puget Sound Health Care System (Seattle/Tacoma, WA)

--Yale University School of Medicine (New Haven, CT)

KEEPS is a randomized, placebo-controlled, double-blind trial of 720 women designed to provide prospective data on the risks and benefits of HT on recently menopausal women, particularly as it relates to heart disease. The results of the Women's Health Initiative (WHI) estrogen plus progestin trial, which was halted by the NIH in July 2002, prompted a consortium of health researchers to study the risks and benefits of HT on a younger subset of women who recently entered menopause. Prior to the WHI, most data suggested that HT was associated with a high degree of protection (30 to 50 percent reductions) against heart disease, all-cause mortality and osteoporotic fractures, in addition to a small increase in breast cancer risk.

KEEPS is designed to explore issues raised by the WHI, specifically:

Age of Participants - The study will explore whether beginning HT in recently menopausal women (six months to three years since last menses) protects against atherosclerosis. WHI participants were postmenopausal, with a mean age of 62.7, yet most women begin HT much younger, at the onset of menopausal symptoms.

Transdermal Application - KEEPS also will study whether the natural human estrogen, estradiol, delivered through the skin via a patch is equally effective as and potentially safer than oral estrogen. Researchers have speculated this method may be safer since transdermal estrogen does not go to the liver in high concentrations and has been shown to have little or no effect on clotting. On the other hand, transdermal estradiol may be less effective since it does less to increase HDL-cholesterol levels.

"There are a lot of data that suggest that estrogen is good early and bad late," said Dr. S. Mitchell Harman, director of KLRI. "The WHI was instrumental in providing a roadmap for the next phase of research to examine whether estrogen protects younger women from cardiovascular disease, as earlier observational studies indicated. KEEPS is designed to provide useful new data to begin answering women's questions and help shape future research."

Study Design

KEEPS will recruit 720 healthy, recently menopausal women ages 42 to 58. Study participants will be divided into three groups. The first group will receive an oral tablet containing conjugated equine estrogens (Premarin(R), 0.45 mg daily) and a placebo skin patch. The second group will receive an oral placebo tablet and a skin patch delivering estradiol (Climara(R), 50 mcg/day). The third group (control) will receive a placebo tablet and a placebo skin patch. Women receiving active estrogen also will use progesterone (Prometrium(R), 200 mg daily for first 12 days of each month) to protect the uterine lining from overgrowth. Subjects not receiving active estrogens will take placebo capsules.

Visit www.keepstudy.org or call [phone] for more info.