DEDHAM, MASS. — Has the backlash against hormone therapy gone too far? Should doctors take yet another look at the evidence and find selective uses for HT that maximize its benefits and minimize its risks?

The answer to both questions is yes, according to Isaac Schiff, M.D., professor of gynecology at Harvard Medical School and chief of the ob.gyn. service at Massachusetts General Hospital. At a symposium on bone health sponsored by Boston University School of Medicine, Dr. Schiff recommended discussing HT with select patients as a double-duty medication for bone health and menopausal symptoms.

“Just as the pendulum went too far in the early 1990s—when all the retrospective studies suggested estrogens prevented heart disease, osteoporosis, Alzheimer's disease—after the Women's Health Initiative [WHI], the pendulum swung way too far to the other side, suggesting that estrogens are too risky,” Dr. Schiff said.

News reports about the WHI trial tended to focus on the risks of HT and to overlook benefits. Estrogen therapy is “certainly one of the most potent agents we have available” for preventing hip, vertebral, and wrist fractures, he said.

When the National Institutes of Health announced the landmark findings of the WHI trial, HT prescriptions declined precipitously. “Overall health risks [of HT] exceeded benefits,” investigators concluded after they stopped the trial early (JAMA 2002;288:321–33).

According to the WHI findings, therapy with estrogen plus progestin was associated with a major increase in the relative risk of several serious health problems. For example, it was tied to a 29% increased risk of coronary heart disease (CHD), a 41% increased risk of stroke, a twofold increased risk of pulmonary embolism (PE), and a 26% increased risk of breast cancer.

Many observers found the absolute risks less alarming, however. According to the WHI data, if 10,000 women took estrogen plus progestin for 1 year, there would be an excess risk of seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers. There would be no extra deaths. Among women with no uterus taking estrogen only, there would be 12 more strokes (JAMA 2004;291:1701–12).

HT would also confer some benefits among those 10,000 women. There would be six fewer colorectal cancers and five fewer hip fractures. Among women with no uterus taking estrogen, there would be six fewer hip fractures. The WHI did not state whether HT would relieve menopausal symptoms.

Dr. Schiff termed the findings on fracture prevention “quite impressive.” Citing the reductions in relative risk, he noted that women taking progestin plus estrogen had a 29% reduction in lower forearm fractures and a 33% reduction in hip fractures. In the estrogen-only arm of the study, there was a 39% decrease in hip fractures and a 38% decrease in vertebral fractures.

Studies of other drugs designed to prevent and treat osteoporosis have had difficulty showing a reduction in hip fractures. The effect of medium-dose HT on fractures “is equivalent to bisphosphonates,” he said.

Hidden amid the WHI data is information on the impact of low-dose estrogens that might help clinicians balance benefits and risks of HT therapy, Dr. Schiff suggested.

At low doses, estrogens increased bone mineral density by 2.4% and 3.9% at the femoral neck and spine, respectively.

Dr. Schiff did not provide evidence from WHI to show that low-dose estrogens were associated with fewer fractures, however. As the NIH noted in a 2000 consensus statement on osteoporosis, improvements in bone density do not always translate to a decrease in fractures. “The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap, but are not identical” (NIH Consens. Statement 2000;17[1]:1–36).

Still, Dr. Schiff said that there is enough evidence to support prescribing low-dose estrogen for the prevention of devastating hip fractures.

Citing data on low-dose oral contraceptives in relatively young, healthy women, Dr. Schiff said that, in theory, lower doses of estrogen should yield fewer health risks in the middle-aged and elderly. And “even very-low-dose estrogen is quite effective at maintaining bone density.”

That said, patients must be thoroughly informed about their individual risk profile regarding HT so they can make informed decisions. “A woman of age 50 is not worried about a hip fracture at age 80,” he said. “She is worried about the potential for breast cancer at age 55.”

And the data on estrogens and breast cancer are mixed. Some studies show an increased risk, some do not. “I tell my patients I personally have major concerns about the long-term risk” of breast cancer associated with estrogen therapy, he said.

In general, Dr. Schiff said that he prescribes estrogens for the minority of women with very severe hot flashes. For vaginal dryness topical estrogen therapy can help. Very-low-dose estrogen will also help with urogenital symptoms.

Don't Write Off Low-Dose HT for Bone Health : Low-dose HT should be considered to reduce fracture risk and menopausal symptoms in certain patients.