Boning up on postmenopausal hormones.

Postmenopausal hormone supplements fight a woman's risk of osteoporosis-a potentially crippling, age-related embrittlement of the bones-better than had been expected, two new studies find. A related study concludes, however, that maintaining sturdy bones beyond a woman's childbearing years may require a troubling trade-off: an elevated risk of breast cancer.

All three studies appear in the Nov. 6 Journal of the American Medical Association (JAMA).

At menopause, a woman's body dramatically cuts its production of estrogen. Besides launching an uncomfortable period of physical adjustment, this change accelerates bone loss and triggers changes in the blood's lipids that heighten the risk of heart disease. The federally funded Postmenopausal Estrogen-Progestin Interventions (PEPI) trial was designed to assess in nearly 900 women age 45 to 64 how well hormone supplements arrest bone loss.

One group received tablets with no active agents. The rest received estrogens-alone or with a progestin, another female sex hormone, in one of three common formulations.

Designers of PEPI hoped the 3-year treatments would halt the rapid bone loss that occurs early in menopause, notes Joan McGowan of the National Institute of Arthritis and Musculoskeletal Diseases in Bethesda, Md. "But PEPI showed that you more than stabilize bone loss," notes McGowan, a coauthor of one of the JAMA reports. "There is actually an increase in the bone at the spine and the hip," she says-the areas most vulnerable to debilitating fractures.

All four hormone treatments increased bone density in the spine by 3.5 to 5 percent and in the hip by 1.7 percent. Smokers derived the most benefit. Untreated smokers lost 3.5 percent of their spinal bone, about twice as much as untreated nonsmokers, but both smokers and nonsmokers on the hormonal therapy gained the same amount of bone.

In a related study, physicians financed by the Parke-Davis Pharmaceutical Research Division of Warner-Lambert tested various doses of an experimental postmenopausal estrogen-progestin mix. They found that low doses of the same two hormones found in most oral contraceptives increased bone at least as well as the available drugs used in PEPI. However, notes study leader Leon Speroff of the Oregon Health Sciences University in Portland, unlike most postmenopausal therapies, the experimental combo does not cause menseslike bleeding in users. He says this drug pair could be marketed next year.

Researchers following almost 7,000 women age 65 and older as part of a fracture risk study decided to look at breast cancer incidence. In the third JAMA article, they report that cancer risk increased in lockstep with bone density. Women who had the most bone in hip or spine showed 2.5 times the risk of women with the least bone.

Though the women were not taking supplemental hormones during the study, the researchers worry that hormone therapy might elevate breast cancer risk, which has been associated with lifetime estrogen exposure (SN: 8/5/95, p. 94).

However, cautions Karl Insogna of the Yale University School of Medicine, coauthor of a commentary in JAMA, "we should not jump to the conclusion that it is estrogen" that links bone density and cancer risk. Until this hypothesis is tested directly, one can't rule out other possibilities, he says.

With the link between hormone therapy and breast cancer unproven, he told Science News, "the take-home message for women on standard hormone-replacement therapy is not to quit."