MEDICATIONS: STATEMENT ON THE ESTROGEN PLUS PROGESTIN TRIAL OF THE WOMEN'S HEALTH INITIATIVE

July 9, 2002 — Today, The American College of Obstetricians and Gynecologists (ACOG) is announcing the formation of a special Task Force on Hormone Replacement Therapy, a multi-specialty panel of medical experts, to make clinical practice recommendations in light of the latest research findings on estrogen/progestin use in postmenopausal women.

Chairing ACOG's Task Force will be Isaac Schiff, M.D., Chair of the Medical Advisory Board to ACOG's Managing Menopause magazine and the Chief of the Vincent Memorial Obstetrics and Gynecology Service at Massachusetts General Hospital in Boston.

ACOG's Task Force, formed in June, will expedite its research review and deliberations in light of recent study findings on the effect of combined estrogen and progestin therapy in women, including today's announcement by the National Heart, Lung and Blood Institute of the National Institutes of Health that it has stopped a major clinical trial on the risks and benefits of this combination therapy in healthy menopausal women. The trial was halted after 5.2 years of an 8-year study, due to an increased risk of invasive breast cancer.

The trial, a part of the Women's Health Initiative (WHI), also found small increases in coronary heart disease, stroke and pulmonary embolism in study participants taking estrogen plus progestin (specifically, 0.625 conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily) compared to the placebo group. While the trial found benefits to the estrogen/progestin combination, including reduced rates of hip fracture and colon cancer, overall the harm was greater than the benefit of the hormone combination. The WHI trial on estrogen use alone is continuing, as study authors report no increased risk for breast cancer in the estrogen-only study group.

A full study report will appear in the July 17, 2002, issue of The Journal of the American Medical Association (JAMA), and is also available today on the JAMA web site at www.jama.com.

The WHI population study group was 16,608 healthy women ages 50 to 79. The data indicate that if 10,000 women take the hormone combination for one year, as compared to 10,000 women not taking the hormone combination,

· 8 more will develop invasive breast cancer

· 7 more will have a heart attack or other coronary event

· 8 more will have a stroke

· 8 more will have blood clots in the lungs

However, among women receiving combination hormone therapy, as compared to the placebo group,

· 6 fewer will have colorectal cancers

· 5 fewer will have hip fractures

The increased breast cancer risk did not appear in the first four years of use. Risks for blood clots were greatest during the first 2 years of hormone use. The reduced risk of colorectal cancer emerged after 3 years of hormone use.

Until ACOG releases final recommendations from its Task Force, ACOG advises the following:

(1) Women who for a number of years have been on the combined estrogen/progestin therapy studied here should not panic, but discuss their individual situation with their physician. The WHI study authors took pains to emphasize that women should not be unduly alarmed. The increased risks in WHI applied to an entire population of women, not to increased risks for individual women — which were very small, less than a tenth of 1 percent per year. The population risks, applied over several years to millions of women, make the increased risks an important public health concern. However, as for individual women, a decision about hormone use should take into account a woman's individual risk for specific conditions that may be harmed or benefited by hormone use.

(2) With respect to women on short-term use of combination hormone therapy for relief of menopausal symptoms, the WHI authors note that although such use was not the focus of this study, it may be reasonable for women to continue use for this purpose, since the benefits are likely to outweigh the risks. Regarding a woman's short-term use of combined estrogen/progestin therapy when indicated for relief of menopausal symptoms, ACOG continues to recommend that this be a personal, individualized decision, made after consultations between a woman and her physician and taking into account a woman's individual benefits and risks from such use.