Chemical Endocrine Disruptors Linked to Early Menopause

Nancy A. Melville

November 05, 2012

SAN DIEGO, California — Women who have been exposed to some well known endocrine disrupting chemicals (EDCs) in the environment show signs of menopause at a significantly earlier age than those who have not been not exposed, according to research presented here at the American Society for Reproductive Medicine (ASRM) 68th Annual Meeting.

Researchers evaluated data collected from 1999 to 2002 on 5708 women in the National Health & Nutrition Examination Survey (NHANES) database. They found that the last menstrual cycle of women who had been exposed to polychlorinated biphenyls (PCBs) was 2.5 years earlier than if they had not been exposed (= .025); if they had been exposed to phthalates, it was 2.3 years earlier (P = .045).

No relation was found between follicle-stimulating hormone levels in menstruating women, the other primary outcome, and any exposure to EDCs. The researchers attributed this to variability in FSH throughout the cycle.

All of the women in the study were 18 years of age or older, were not currently pregnant or breast-feeding, were not using estrogen therapies, and had both ovaries intact.

Women were considered to have been exposed to EDCs (dioxin, PCB, phthalate, and phytoestrogen) if lipid-adjusted serum or urine values fell above the 90th percentile. Adjustments were made for race, ethnicity, body mass index, tobacco and alcohol consumption, parity, and breast-feeding history.

Dioxin and Phytoestrogen Not Related to Early Menopause

Two of the chemicals tested, dioxin and phytoestrogen, showed no association with an earlier age of menopause.

In previous research, EDCs were shown to interfere with the synthesis and metabolism of reproductive hormones. However, evaluation of their role in ovarian function has been lacking.

"This is the first study to demonstrate the potential effect of [EDCs] on ovarian reserve," the researchers write.

"PCBs and phthalates, products known for their long half-lives and worldwide human exposure through diet and plastics, are associated with a significantly earlier age of menopause," they conclude.

Mechanisms Unclear

The actual mechanisms that alter when a woman experiences menopause remain unclear, said lead author Amber R. Cooper, MD, MSCI, from the division of reproductive endocrinology and infertility at Washington University in St. Louis, Missouri.

"The thought is that [EDCs] disturb normal endocrine systems in the body, and menopause is just one of them," she told Medscape Medical News.

Whether the actual mechanism involves changing a receptor in a hormone or something at a cellular level is just not clear, and it could be that some chemicals work in different ways than others, she explained.

Validation Studies Underway

More research is needed to better understand those mechanisms. Dr. Cooper and her team are working to validate their findings in nearly 10,000 women.

"We know there is very much an inheritable, genetic factor in determining the age of menopause, but if we are seeing earlier menopause due to exposure to a broad number of environmental toxins, we definitely need to research this in much more detail, prospectively, and with larger databases," Dr. Cooper noted.

Rebecca Z. Sokol, MD, president-elect of the ASRM, agrees that the findings, although intriguing, are inconclusive.

"The key word with this research is trend, which tells us that it did not meet statistical significance," said Dr. Sokol, who is professor of obstetrics and gynecology and medicine at the Keck School of Medicine, University of Southern California, in Los Angeles.

"I always caution people that it is important to understand that these are associations — not cause and effect. We can't say that these women had early menopause because they had all these chemicals in their urine," she noted.

Determining the true nature of the risk will likely require not only larger numbers, but longer periods of time, Dr. Sokol explained.

"The ideal method would be case–control studies of thousands of subjects, and then follow-up on a regular basis to look at reproductive outcomes. It could take 20 years, but that would be a more cause-and-effect kind of study than cross-sectional," she said.

This study was supported by an ARC grant. Dr. Cooper and Dr. Sokol have disclosed no relevant financial relationships.

American Society for Reproductive Medicine (ASRM) 68th Annual Meeting. Abstract O101. Presented October 22, 2012.