Two Compounds Disrupt Female Hormones

Their influence could cause miscarriage, breast cancer, study suggests

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HealthDay Reporter

MONDAY, April 19, 2004 (HealthDayNews) -- An industrial solvent and a medication often used for seizures and bipolar disorder increase the activity of female hormones inside cells, which might lead to miscarriages and breast cancer in women, a new lab study suggests.

The effects could be especially pronounced in women who are also taking hormones in the form of oral contraceptives or hormone replacement therapy.

The industrial solvent is ethylene glycol methyl ether (EGME), used in the paint and semiconductor industries, while the drug is valproic acid or Depakote. Both are short-chain fatty acids.

"It's not a major alarm. It's basically another piece in the puzzle" of hormones' effects on women, said Donald P. McDonnell, senior author of the study appearing in this week's issue of the Proceedings of the National Academy of Sciences. McDonnell is a professor of pharmacology and cancer biology at Duke University School of Medicine.

The findings so far have only been documented in a laboratory setting, leading some experts to question the significance of the research.

"Depakote has been out there for 20 years. It's one of the oldest branded products on the market," said Catherine Bryan, a spokeswoman for Abbott Laboratories, which makes the drug. "We have 20 years of patient experience and there's no evidence of breast cancer. This can't be extrapolated to humans."

"It [the finding] is interesting... but remember that these are reports of tissue cultures and cells in Petri dishes," added Dr. Steven Goldstein, a professor of obstetrics and gynecology at New York University School of Medicine. "These are not clinical trials. I don't want to read too much into this."

Hormone replacement therapy has received a lot of attention lately, largely due to the publication of results from the U.S. government-funded Women's Health Initiative, which found postmenopausal women taking the therapy have an increased risk for breast cancer.

The authors of the new study wanted to see if there were environmental factors that might affect how humans respond to hormones.

"We designed assays in cells to screen for chemicals that would change the way that cells would see estrogen," raising the specter of potential health problems, McDonnell explained. "What we found rather dramatically in the first half of the study was EGME increases the activity of estrogen and progestin up to tenfold."

Because valproic acid has a similar chemical structure to EGME, the authors tested that compound next. "It did exactly the same thing," McDonnell said. "It functioned to boost the ability of cells to respond to estrogen and progestin."

McDonnell is careful to point out that it's not clear whether this is a good or bad thing, only that "this is a confounding factor in the decision as to how a woman is going to respond to hormones." Any effect would be exaggerated in women taking oral contraceptives or hormone replacement therapy, he said.

Dr. Gina Solomon, a senior scientist at the Natural Resources Defense Council, said, "This study really shows how industrial chemicals and drugs may interact and how industrial chemicals and our own hormones can interact. That makes everything much more complicated."

Although McDonnell downplayed the alarm factor, he does believe the findings should be acted upon right away. "It's going to add another piece of information to a physician when he's trying to work out with the patient the relative risks and benefits" of hormone therapy or oral contraceptives, McDonnell said. "It should be taken into account right now."

Solomon said screening tests that analyze chemicals' effects on humans should take into account the type of compounds used in the study. "There was a focus [in screening tests] on chemicals that bind to a hormone receptor and the authors point out quite rightly that these chemicals [used in the study] would probably not be picked up in initial screens recommended under the screening program... We need to figure out a way to plug this gap in terms of routinely screening chemicals," she explained.

"I would definitely want to talk to my doctor but I wouldn't recommend that people make changes in their medications based on this study without first having a good, long talk with their doctor," Solomon added.

More information

For more on hormone therapy, visit the National Institutes of Health or the National Women's Health Information Center.

SOURCES: Donald P. McDonnell, Ph.D., professor, pharmacology and cancer biology, Duke University School of Medicine, Durham, N.C.; Steven Goldstein, M.D., professor, obstetrics and gynecology, New York University School of Medicine, New York City; Gina Solomon, M.D., senior scientist, Natural Resources Defense Council, San Francisco; Catherine Bryan, spokeswoman, Abbott Laboratories, Abbott Park, Ill.; April 19-23, 2004, Proceedings of the National Academy of Sciences

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