updated 4/20/2004 12:34:52 PM ET 2004-04-20T16:34:52

Women considering hormone therapy should be screened for exposure to a common chemical and a widely used drug, both of which can boost hormone activity to potentially dangerous levels, researchers suggest.

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Millions of women have faced a dilemma about whether to use hormones as they confront reports that long-term use of estrogen slightly increases the risk of stroke and possibly of dementia. The government halted the nation’s last major study of the hormone in March, a year early, because of the safety concern.

Studies also indicate that even more risk is involved in taking the two-drug combination of estrogen and progestin, which boosts the risk of breast cancer and heart attacks.

Now a research team led by Donald P. McDonnell of Duke University suggests that, for some women at least, part of the problem may be associated with prior exposure to other chemicals that can boost the activity of estrogen and progestin.

McDonnell, whose study is based on cultured human cells, mostly breast cancer cells, and on work in mice, is urging that humans be screened for exposure to the chemicals.

Dr. Jacques Rossouw of the Women’s Health Initiative at the National Institutes of Health said, however, that the research is basic and warned that it would be premature to introduce screening for women based on its results.

While the findings may add a new level of concern to women considering hormone therapy, McDonnell said, “it’s probably good news” for them. Knowing that these chemicals have an impact on the hormone action, “you may be able to parse out those women who are at higher risk for adverse effects.”

Dangerous chemicals
McDonnell and his colleagues focused on ethylene glycol methyl ether — EGME — an industrial solvent found in varnishes, paints, dyes, fuel additives and used in the semiconductor industry; and valproic acid, which has a similar chemical structure to EGME and is among the top 100 drugs prescribed in the United States. It is used to treat bipolar disorder, seizures and migraines.

Both these chemicals significantly increase the action of hormones in the body, McDonnell reports in this week’s issue of Proceedings of the National Academy of Sciences.

“Our study demonstrates that these chemicals boost the activity of estrogens and progestins inside cells eight- to 10-fold,” said McDonnell. “These data should prompt caution for patients who are exposed to either of these chemical compounds while taking any estrogen- or progesterone-containing medications, such as hormone therapy, oral contraceptives or tamoxifen for breast cancer.”

Scientists have long had misgivings about chemicals in the environment that seem to mimic estrogen, fearing that these may lead to various illnesses.

McDonnell’s study focused on two similar chemicals that were known to affect the reproductive system, reducing sperm count in men and producing irregular ovulation and spontaneous abortion in women.

What the researchers found was not that the chemicals mimic estrogen, but rather they sensitize the cells to it by inhibiting enzymes inside cells that normally slow the process of gene transcription. The result is to speed up cell activity, which potentially can fuel cell growth beyond what is normal, the researchers said.

“Estrogen produces effects inside cells in a very tightly controlled manner, so skewing that process by accelerating transcription can produce a variety of problems,” said McDonnell.

“Clearly, these chemicals are affecting the cellular environment where estrogen works, and our goal would be to identify other chemicals with the same effect and alert the public to the potential for such drug-drug interactions,” he added.

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