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"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 tradeoff: an elevated risk of breast cancer.

All three studies appear in the Nov. 6 1997.
Journal of the American Medical Asociation (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 (PEPl) 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 cornmon 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 PEP1 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 onsmokers, but both smokers and non-smokers 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 menses like 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 lnsogna 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.” J. Raloff

High Bone Mass Hints At Breast Cancer Risk 

Although long suspected, the link between high estrogen levels and breast cancer risk has never been proven -in part because long-term estrogen levels are difficult to measure. New data collected from the Framingham Study show that bone mineral density may be a marker for cumulative estrogen exposure and breast cancer risk in postmenopausal women.

While measuring bone densities of 1,373 women (ages 47 to 80) during a four-year period, researchers found that breast cancer risk doubled among women with bone mineral density levels in the highest quartile of bone mass as compared to women in the lowest quartile. High bone mass density is related to high estrogen levels. Forty-four women in the highest bone density quartile developed breast cancer, whereas only 12 women in the lowest quartile did.

The study did not include family history of breast cancer as a risk factor. Women with such family histories are two to three times more likely to develop breast cancer than other women. Research results are particularly significant for women with genetic risk factors whose breast cancer risk may increase if they take estrogen replacements. Conversely, women with a family history of osteoporosis and no breast cancer may want to consider some form of estrogen replacement.

Principal investigator Yuqing Zhang, Ph.D., says, “Although the biological mechanisms  linking bone mass to the risk of breast cancer are not fully understood, cumulative exposure to estrogen may have a role.” Further studies measuring long-term estrogen levels are needed to affirm Zhang’s hypothesis. -New England Journal of Medicine Feb. 27, 1997.
Nutrition Science News l May 1997 -Vol. 2, No. 5 213

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