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EGME/Depakote Boost Estrogen/Progestin In Cells

Solvent and Common Drug Raise Breast Cancer Risk

Researchers have identified an industrial solvent in the environment, EGME, and a frequently prescribed drug, valproic acid, as compounds that so potently boost estrogen and progestin activity inside cells that they likely trigger the reproductive failures-and potentially even breast cancers-seen among women exposed to these chemicals.

Ethylene glycol methyl ether (EGME) is an industrial solvent found in varnishes, paints, dyes, fuel additives and the semiconductor industry.

Valproic acid (trade name Depakote) has a similar chemical structure as EGME and is among the top 100 drugs prescribed in the U.S., used to treat bipolar disorder, seizures and migraines.

Moreover, many women who are unknowingly exposed to these compounds could be at increased risk for hormonally related cancers, miscarriages and irregular ovulation, said the researchers from the Duke Comprehensive Cancer Center and the department of pharmacology and cancer biology at Duke University Medical Center.

Their findings suggest that estrogen and progestin alone may not be the sole triggers for the increased risk of invasive breast cancers in postmenopausal women who take hormone replacement therapy.

Rather, it may be that select women who are exposed to hormone-sensitizing compounds are put at higher risk for cancer and cardiovascular events.

In fact, there may be dozens or even hundreds of similar compounds throughout the environment that can sensitize cells in the body to hormones such as estrogen, progestin and even testosterone, said Duke pharmacologist Donald McDonnell, Ph.D.

Such compounds are known as "endocrine disrupters" because they alter the normal course and behavior of hormones in the body.

McDonnell is principal investigator of a study describing these results, which were published in the Proceedings of the National Academy of Sciences. The lead author is Michelle Jansen, Ph.D., pharmacology research associate at Duke.

"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."

McDonnell said the activities of these compounds wouldn't necessarily be deleterious in all cases, but they do mandate vigilance by the medical community because the duration of exposure to estrogens, progestins and androgens is associated with increased risks of breast, ovarian and prostate cancers.

SOURCES: Proceedings of the National Academy of Sciences, April 19, 2004 Duke University Medical Center (http://www.duke.edu)

Thanks to Artemis, Johns Hopkins newsletter, 5/04

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