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NIH Conference Addresses Hormone Therapy Issues

Kate Traynor

National Institutes of Health (NIH) Director Elias A. Zerhouni recently summed up the reaction of the public and the medical community to the unexpected finding this past summer that one type of hormone replacement therapy seems to do more harm than good.

"Contrary discoveries are more unsettling than others, and I think we are experiencing that," Zerhouni said at the close of the October 23–24 NIH workshop >on menopausal hormone therapy.

The workshop was held to address concerns that arose from a Women’s Health Initiative (WHI) study (see August 15, 2002, AJHP News) on the disease prevention benefits of combination estrogen–progestin therapy. The study was halted suddenly this summer—three years before the planned end date—because of evidence that the treatment had increased the participants’ risks of breast cancer, stroke, and myocardial infarction.

Before the publication of data from the WHI study, long-term hormone therapy had been widely prescribed to millions of women for the prevention of cardiovascular disease as well as for relief from menopausal symptoms. But WHI data indicated that combination hormone therapy increased a woman’s risk of having a stroke by 41%. The treatment also conferred a 29% increase in the risk of myocardial infarction and a 26% increase in the risk of invasive breast cancer.

Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, reminded workshop attendees that "no estrogen or progesterone product has ever been approved for the prevention of cardiovascular disease or for hormone replacement."

"The indications for which drugs have been approved by the FDA for menopausal conditions," Woodcock said, "are the symptomatic treatment of vasomotor symptoms—hot flashes, they’re called—the treatment of vulvar [and] vaginal atrophy, and the prevention of osteoporosis."

The NIH conference was held about a week after the U.S. Preventive Services Task Force (USPSTF) released its new recommendations on combined hormone therapy. During the NIH conference, task force Vice Chair Janet D. Allan, dean of the University of Maryland School of Nursing in Baltimore, summarized USPSTF’s opinion: "The harmful effects of estrogen and progestin are likely to exceed the chronic disease prevention benefits in most women."

Noting that USPSTF did not evaluate the use of estrogen–progestin therapy to alleviate menopausal symptoms, Allan said that "the balance of benefits and harms for an individual woman will be determined by her personal preferences, individual risks for specific chronic diseases, and the presence of menopausal symptoms."

Because data from the WHI study had indicated that combination hormone therapy reduced women’s risk for hip fracture and colorectal cancer, Allan said some women might decide that the treatment is worthwhile for them.

"We are recommending that clinicians use a shared decision-making approach with women to address the issues of preventing chronic diseases such as fracture, cardiovascular disease, and cancer," Allan said. Nevertheless, she added, "we are urging clinicians to discuss other effective strategies for preventing osteoporosis and fractures."

The WHI study evaluated one combination hormone product, Wyeth Ayerst’s Prempro, containing 0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate. Prempro’s labeling has already been changed to reflect information gleaned from the WHI study. FDA’s Woodcock said her agency is examining the implications of the WHI study on the labeling of the assortment of estrogen–progestin products on the market.

"When we look at a specific product, there is an issue of composition, and there is an issue of dose," Woodcock said. Prempro, she added, contains a mixture of estrogens that have not been pharmacologically well characterized and differs in composition from other hormone therapy products.

"The WHI results provide important additional risk information on estrogen–progestin combinations, leading us to evaluate the whole area," she said. "But quantitative extrapolation to similar products, unfortunately, is not possible."