Early Estrogen Therapy May Reduce Cardiovascular Risks

New Haven, Conn. — A new analysis of both estrogen and estrogen plus progestin data from the Women’s Health Initiative (WHI) hormone trials in the Journal of the American Medical Association shows a 24 percent reduction in risk for coronary heart disease events in women starting hormone therapy less than 10 years after menopause.

The analysis, by researchers at Yale and eight other study centers participating in the Kronos Early Estrogen Prevention Study (KEEPS), also showed a 30 percent reduction in overall deaths among women aged 50 to 59 using hormone therapy.

However, the new study, “Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause,” also found that hormone therapy increased coronary heart disease events by 28 percent in older women, and that deaths increased by 14 percent in women aged 70 to 79. There was a slightly elevated risk of stroke at all ages studied.

The Women’s Health Initiative was halted in July 2002 due to overall elevated risks. This new analysis indicates that excess cardiovascular risk is confined to older women, which is consistent with previous research. Prior to the WHI, most data suggested that hormone therapy was associated with a high degree of protection (30 to 50 percent reductions) against coronary heart disease, all-cause mortality, and osteoporotic fractures, in addition to a small increase in breast cancer risk.

“This new analysis of WHI data seems to confirm earlier findings that estrogen may be good early, but bad late,” said Dr. S. Mitchell Harman, director of the Kronos Longevity Research Institute. The Institute is conducting the KEEPS, a randomized, controlled, double-blinded trial of 720 women designed to provide prospective data on the risks and benefits of early menopausal hormone therapy, particularly as it relates to the progression of atherosclerosis.

“In this study, hormone therapy reduced overall mortality in the younger menopausal women,” said lead investigator of the KEEPS trial at Yale, Hugh S. Taylor, M.D., associate professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences and Molecular Cellular & Developmental Biology. “It is important not to trivialize quality of life. No one should tell women to put up with hot flashes to avoid serious risk, if in reality this therapy saves lives.”

The KEEPS will also examine 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 that 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 disease.

“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, said Harman. “KEEPS is designed to provide useful new data to begin answering women’s questions and help shape future research.”

For more information on KEEPS, visit http://www.keepstudy.org or contact Diane Wall, clinical research nurse coordinator at 203-785-4739 or diane.wall@yale.edu.

In addition to Yale, the KEEPS study centers include:

• Albert Einstein College of Medicine of Yeshiva University/Montefiore Medical Center, Bronx, NY
  
• Columbia University College of Physicians and Surgeons, New York, NY
  
• Harvard Medical School/Brigham and Women’s Hospital, Boston, MA
  
• Kronos Longevity Research Institute, Phoenix, AZ
  
• Mayo Clinic College of Medicine, Rochester, MN
  
• University of California-San Francisco/Center for Reproductive Health, San Francisco, CA
  
• University of Utah School of Medicine, Salt Lake City, UT
  
• University of Washington School of Medicine, Seattle, WA

Citation: JAMA, Vol. 297, No. 13, (April 4, 2007)