Estrogen: friend or foe? - includes related article

FDA Consumer, April, 1995 by Marilynn Larkin

"Sperm counts down worldwide." "Environmental estrogens linked to reproductive abnormalities and cancer."

These and other startling--and possibly misleading--headlines are based largely on results of recent research that appears to show an association between estrogen-like compounds in the environment to everything from "feminized" wildlife to reproductive problems in humans. While some scientists believe these findings are cause for concern, other researchers are convinced such fears are exaggerated.

"I know of no evidence that any industrial products are affecting human health," says Dan Sheehan, Ph.D., a research biologist in FDA's National Center for Toxicological Research. "There is some evidence for adverse effects to wildlife in highly polluted sites. But this hypothesis needs to be tested very carefully before any conclusions can be drawn."

Environmental estrogens come from many sources, Sheehan explains. One source is industrial products and byproducts, such as chemicals used to make plastic packaging, or those contained in pesticides. Estrogens and estrogen-like compounds may also be used as ingredients in cosmetics. Phytoestrogens are naturally occurring compounds in plants. And, of course, millions of women take estrogen pills for birth control and menopausal hormone replacement therapy.

Environmental estrogens, also known as "estrogen mimics" or "estrogen modulators," may be ingested, breathed in from the air, or absorbed through the skin. Some are considered "estrogenic"--meaning they imitate or enhance the effects of estrogen in the body; others are "anti-estrogenic"--they block or interfere with the body's use of estrogen (see accompanying article). The estrogen-like compounds bind to estrogen receptors in cells, which may lead to changes in the cells, tissues or organs.

Medical Uses of Estrogen

Millions of women increase the estrogen in their bodies when they take oral contraceptives or pills to relieve symptoms associated with menopause, such as hot flashes, sweating, and vaginal dryness. Certain estrogen drugs (Premarin, Ogen, and Estrace tablets, and Estraderm patch) also are approved to prevent osteoporosis. In addition, estrogens may be used to treat some forms of infertility and menstrual disorders.

Estrogen drugs may cause side effects such as bloating, weight gain, breast tenderness, and nausea. Women who take estrogen to treat menopausal symptoms should be closely monitored by a physician, and all women age 50 or older are advised to have regular mammograms, according to Enid Galliers, an FDA consumer safety officer.

The pills should be taken only when there is a "well-defined need," she says. "If a woman is not at high risk for osteoporosis and doesn't have unmanageable symptoms," she should carefully weigh the risks and benefits of estrogen in consultation with her health-care provider before making a decision about estrogen. She adds that estrogen drugs may increase the risk of uterine cancer in postmenopausal women who have not had a hysterectomy.

Do oral contraceptives promote or accelerate breast cancer? "The jury is still out," says Galliers. "If a woman has a family history of breast cancer, she might want to use another birth control method or be monitored closely by a physician."

Pregnant women should not take drugs containing estrogen because of the "potential harm of estrogen to the fetus, including a greater risk of birth defects in the reproductive system," she notes. It is this concern that is behind some scientists' belief that estrogen-like chemicals in the environment may have similar harmful effects, FDA's Sheehan adds. However, the effects of drugs that contain estrogen occur at therapeutic doses; levels of environmental estrogens may be much lower.

DES

"Because of what happened with [pregnant women taking] DES, we're concerned about the potential developmental toxicity of all estrogen-like chemicals, whether they are naturally occurring or industrial products," Sheehan says. "We must ask the question, 'Can this chemical have adverse effects on the fetus?' Right now, our database in this area is woefully inadequate. It is critical that more studies be done."

DES (diethylstilbestrol) is a drug that mimics a specific type of natural estrogen hormone called estradiol. DES, like other estrogen drugs, may be prescribed to treat advanced breast and prostate cancer, but is no longer recommended for use in healthy women. Potential side effects are the same as for other estrogen drugs.

In the 1950s and 1960s, DES was prescribed to millions of women in the United States and Europe to prevent miscarriage. This use was abandoned when it was learned that the children of women who took the drug during pregnancy have a high incidence of reproductive tract abnormalities and may be at increased risk for various types of cancer. Some researchers consider what happened to these children a model of what may happen to others who are exposed to estrogenic chemicals during intrauterine life.

Pesticides