New studies raise concerns over hormone therapy

Fosamax used for women at risk of breast cancer

Although researchers have long accepted that hormone replacement therapy (HRT) is effective in combatting osteoporosis, a dizzying number of new studies raises serious questions about when women should begin replacing estrogen and whether some women should choose an alternate therapy.

In one recent study, published in the New England Journal of Medicine (1997; 336:611-617), researchers at Boston University found a correlation between high bone density in women and breast cancer. The researchers studied 1,373 women between the ages of 47 and 80 and found that those with relatively higher bone density were as much as three times more likely to develop breast cancer than women with lower bone density.

The researchers theorize the reason for the correlation is estrogen, which stimulates bone growth. "If a woman naturally has a lot of estrogen around, she’s also probably going to have healthier bones," says Ethel Siris, MD, director of the Toni Stabile Center for the Prevention and Treatment of Osteoporosis at Columbia Presbyterian Medical Center in ew York City. "But having a lot more estrogen around might increase her long-term risk of breast cancer."

Another study, published in The Journal of the American Medical Association (1996; 276:1,404-1,408) provides further evidence, suggesting that for every standard deviation from the mean increase in bone mineral density, a woman has a 30% to 50% greater risk of developing breast cancer.

Jane A. Cauley, DrPH, associate professor in the department of epidemiology at the Graduate School of Public Health at the University of Pittsburgh, and lead author of the JAMA study says that such research is important because it allows women to make more informed choices about the use of HRT, taking into account possible negative effects. But some scientists think Cauley’s findings are nothing new.

"Bone density correlates with a woman’s estrogen environment, and we’ve long known that a small percentage of women that get breast cancer have characteristics that are associated with more estrogen exposure," says Leon Speroff, MD, professor of OB/GYN at Oregon Health Sciences University in Portland. Remember that the majority of women who get breast cancer have no such risk factors, Speroff says.

Nevertheless, women with a family history of breast cancer might consider postponing HRT until their later years, says Diane L. Schneider, MD, a professor of medicine at the University of California, San Diego. In another JAMA reported study (1997; 277:543-547), Schneider and her colleagues found that women who begin taking estrogen after the age of 60 can achieve almost the same increase in bone density as women who began HRT at menopause.

"This is something that’s been argued about by a number of people, who say, ‘Gee, if long-term estrogen use has dangers, and if you can get the same bone benefits by taking it later, why not do that?’" says Siris. Siris notes, however, that a number of other studies do not support the contention that long-term estrogen puts women at risk of breast cancer. "Some people would say that the benefit to an individual woman would probably be greatest if she takes estrogen early in menopause so that she doesn’t lose any bone to begin with, rather than jumping in after she’s already lost bone." Siris adds that it’s also important to consider studies indicating that estrogen can have positive effects for women at risk of heart disease.

Given the proliferation of studies concerning HRT, it’s not surprising that few hard and fast national guidelines exist to direct providers in the care of patients at risk of osteoporosis. At the moment, the decision of whether to recommend HRT depends largely on the circumstances of the individual patient. "For example, if you have a woman with average bone mass, an 80-year-old mother who never broke a bone, and no family history of heart attack, but there’s a maternal great aunt with breast cancer, then that woman might decide she doesn’t want to do anything right away," says Siris.

Another option

One alternative for women who choose to avoid HRT is the drug Fosamax, developed by the West Point, PA-based pharmaceutical firm Merck and Co. Fosamax won FDA approval as a treatment for osteoporosis in 1995 and is now slated to be approved for prevention of the condition.

Fosamax works by "turning off" the cells (osteoclasts) that break down bone, while not affecting osteoblasts, the cells that build bone. The result is a net increase in bone mass. Shutting down the osteoclasts is important because during the first five to seven years following menopause, women can lose up to 25% of their bone mass, says Maria Evans, manager of public affairs at Merck.

Although no evidence indicates that Fosamax increases a woman’s risk of breast cancer, the drug also has no apparent cardiovascular benefits. "It’s bone specific, and it would resolve the bone issue without having to deal with the hormone," says Siris. "But it would certainly not do any good or harm to the woman’s heart. It wouldn’t do anything at all except to her bones. Some women like that, especially if they have a family history of breast cancer."