Estrogen helps some more than others.

The so-called bad cholesterol, LDL, can come in two sizes--big, buoyant particles and small, dense ones. The latter lodge in blood vessel walls more easily.

Researchers now find that women who have the smaller form of LDL are at higher risk of heart disease but are also more likely to see cholesterol reduction from hormone-replacement therapy. Genetics determines which type of LDL predominates, says H. Robert Superko, a cardiologist at Berkeley HeartLab in San Mateo, Calif., and the Lawrence Berkeley (Calif.) National Laboratory.

In a study of 44 postmenopausal women, average age 58, Superko and his colleagues gave half of the women estrogen and half an inactive substance; after 4 months, each received the other substance for 4 months more. Estrogen cut LDL cholesterol by 15 percent among the women with the smaller form, compared with 4.6 percent for women with the larger form.

While only 8 to 10 percent of premenopausal women in the general population have the smaller form, known as pattern B LDL cholesterol, that percentage jumps to 30 to 40 percent after menopause. "Something happens during menopause where this inherited trait starts expressing itself," he says.

Estrogen is often prescribed to reduce osteoporosis risk, hot flashes, and other menopausal symptoms. Researchers have established that it also can protect against heart disease, although the mechanism by which it does so is not clearly known. The hormone may suppress the gene that influences LDL patterns and place some women at risk, Superko speculates.

This study calls into question the use of estrogen replacement strictly as a cardiovascular aid to lower LDL cholesterol in women with the larger form of LDL, or pattern A, he says.

A commercially available test to determine whether a person's LDL is pattern A or B costs about $160. Roughly 7,000 doctors routinely send blood samples to Berkeley HeartLab for this analysis, Superko says.