Designer Estrogens

Science News, Oct 16, 1999 by Damaris Christensen

As the baby boomers reach retirement age, the need to judge the costs and benefits of hormone-replacement therapy presses on more women than ever before. If the promise of designer estrogens comes true, a woman's decision about whether to take a drug to combat postmenopausal health problems could become much simpler. Researchers agree, however, that there is no perfect designer estrogen--yet.

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RELATED ARTICLE: Closing the gender gap

Men needn't feel left out as pharmaceutical companies pursue novel designer estrogens. Many companies hope to develop a designer estrogen, or selective estrogen receptor modulator (SERM), that men can take to prevent heart disease. First, though, scientists need to develop an estrogen that does not promote breast growth--a side effect few men are willing to tolerate.

"Men have a higher risk of heart disease, and this is presumably related to a lack of estrogen," says JoAnn E. Manson of Harvard Medical School in Boston. "SERMs might have a role in narrowing the heart-disease gap between men and women."

The basic molecular biology of the estrogen receptors seems to hold true for other hormone receptors, says Donald P. McDonnell of Duke University Medical Center in Durham, N.C. This means that researchers can create designer drugs with selective effects on these receptors, he says.

Some scientists are considering androgen, the male sex hormone. Selective androgens that build muscle and bone--but avoid the unwanted hair growth triggered by natural androgen--could help treat the muscle wasting caused by cancer or AIDS, says McDonnell. A few studies have suggested that small amounts of androgen may increase a woman's libido. Because androgens can trigger prostate cancer, it's important to ensure that any designer androgen prescribed to men has little effect in the prostate, says Andres Negro-Vilar of Ligand Pharmaceuticals in San Diego.

Researchers are also looking to design variations on glucocorticoids, which physicians often prescribe to reduce inflammation in chronic diseases like arthritis in both sexes. Natural glucocorticoids increase a patient's risk of developing hypertension, diabetes, and osteoporosis.

Finally, progesterone, a female sex hormone frequently prescribed to women as a contraceptive, has several unwanted side effects. It can trigger mood swings, fluid retention, and breast tenderness. Drug companies hope to develop selective progesterone-receptor modulators with none of these side effects.

Designer androgens, glucocorticoids, and progesterones have just begun to be tested in people, but Negro-Vilar is optimistic. After all, he says, "once we learned it could work for the estrogen receptor, why not for others?"

--D. C.