Women benefit from low dose of estrogen.

Even as evidence accumulates that hormone-replacement therapy increases the risk of breast cancer and heart attack, stroke, and other vascular problems, one benefit of giving estrogen to older women has remained untainted: bone preservation.

Scientists now report that even a tiny dose of estrogen can boost bone density in elderly women significantly better than no dose at all. Moreover, the small dose apparently doesn't cause an increase in the kinds of adverse effects that have driven women away from hormone therapy. On the other hand, aside from fewer headaches, this dose of estrogen didn't provide relief from postmenopausal symptoms, such as bloating and breast tenderness. The new findings appear in the Aug. 27 Journal of the American Medical Association.

The researchers enlisted 167 healthy women over age 65 and randomly assigned 83 of them to get a pill containing one-quarter the typical dose of estrogen and 84 to receive an inert pill. All participants also took vitamin D and calcium daily.

In addition, except for women who had previously undergone a hysterectomy, the study volunteers received the female hormone progesterone for 2 weeks every 6 months. Although this results in a dose of progesterone considerably smaller than that typically given in combined progesterone-estrogen therapy, it prevented the abnormal thickening of the uterine lining that can arise from estrogen-only therapy, says Karen M. Prestwood of the University of Connecticut Health Center in Farmington.

Over 3 years, the women getting the inert pill had a 1 percent increase in bone density, while women taking estrogen averaged a 2.3 percent increase, a significant difference.

Blood and urine samples revealed that the women on estrogen had lower amounts of two chemicals associated with bone degradation.

Meanwhile, adverse effects from the estrogen therapy were minimal over the 3 years. For example, the women receiving the hormone and those receiving the inert pills had roughly the same incidence of abnormal mammograms.

"There's been a wave of discontinuation of estrogen [therapy] across the country," says Robert P. Heaney of Creighton University in Omaha, Neb. These and other findings may cast the hormone in a new light, he says. "I'm quite sure the pendulum is going to swing back."

Heaney suspects that taking estrogen orally is part of the problem. Whereas naturally produced estrogen spreads gradually throughout the body, a pill produces a hormone surge that has strong effects on the liver. The surge might induce the organ to make blood-coagulation factors, he says, which contribute to vessel blockages, heart attack, and stroke. Estrogen delivered by a skin patch largely bypasses the liver, Heaney says. In the Aug. 9 Lancet, French scientists report that postmenopausal women taking estrogen by patch have less clogging in their veins than those taking the hormone orally do.

Oral estrogen also seems to enhance the liver's synthesis of C-reactive protein, a compound implicated in heart disease, Prestwood says. Further tests should investigate ultralow-dose estrogen delivered by patch and should compare bone-fracture rates in women on estrogen versus those on a placebo, she says.