The impacts of toxic ‘forever chemicals’ aren’t the same for women, men

May 1, 2024

This story is part of a series, “Fighting ‘Forever Chemicals’: Women face pervasive PFAS risks.”

While “forever chemicals” have been linked to numerous adverse health impacts from cancers to kidney disease, they also may have disparate impacts on male and female bodies.  

“Very often you see something in one sex and not the other sex,” said Linda Birnbaum, former head of the National Institute of Environmental Health Sciences and the National Toxicology Program. 

“Forever chemicals,” or PFAS, can be found in many common household products and certain kinds of firefighting foams. Their use in manufacturing has led their proliferation in the air, water and soil, and they are estimated to be in the blood of about 97 percent of Americans. The federal government recently set the first nationwide limits on a few types of these substances in drinking water.

Some of the different ways the pervasive chemicals affect men and women are clearly tied to reproductive organs. 

PFAS exposure is associated with an increased risk of testicular cancer, for example: A panel of scientists established in 2012 that there is a “probable link” between exposure to a type of PFAS called PFOA and testicular cancer.

A January 2022 Toxicology review explored several issues related to the female reproductive system — such as birth defects, fertility and menstrual cycle changes — that could be connected to PFAS exposure. “The effects are many,” the authors found, though they said it’s not yet clear exactly how the substances target female endocrine and reproductive systems due to “a major research gap.”

A study published in September sought to narrow that gap by zooming in on sex-specific relationships between three classes of probable endocrine disruptors — including PFAS — and previous diagnoses of hormone-related cancers. The scientists observed particularly striking indications of these differences with regard to melanoma: Higher blood levels of PFAS were linked to prior diagnoses in women, but not in men. 

“Sex-specific associations between PFAS chemicals and previous melanoma diagnosis, suggest that sex-mediated mechanisms may be at play,” wrote the authors, from the University of Southern California and the University of Michigan.

While the precise mechanism behind the melanoma connection is still uncertain, the scientists surmised that because these tumor cells have estrogen receptors, environmental contaminants that mimic estrogenic activity — such as PFAS, potentially — could be fueling the cancer’s growth in women.

Similar to melanoma, other health impacts that aren’t so obviously tied to sex-specific characteristics may still affect men and women differently following exposure to environmental contaminants, such as PFAS.

High blood pressure, for instance, appears to be more pronounced in women than in men, recent studies have revealed.

Sometimes, this manifests in pregnancy-induced hypertension, which can lead to a potentially fatal condition called preeclampsia — a potential effect of PFAS exposure that Erin P. Hines, a researcher in the Environmental Protection Agency’s reproductive toxicology division, said she’s eager to see more research into.

“Having preeclampsia or having pregnancy-induced hypertension during pregnancy can change a woman’s health outcome for the rest of her life, putting her more at risk for adverse cardiovascular outcomes like stroke,” Hines said, noting that this risk is independent of PFAS exposure.

“But if you have a pregnancy where you have preeclampsia or one of these hypertensive disorders of pregnancy, over your lifetime, there are increased risks of morbidity and mortality associated [with] cardiovascular events,” she added.

Beyond the pregnancy-induced type, additional research has also identified hypertension in the PFAS-exposed female population broadly. 

A 2022 study from the American Heart Association found that middle-aged women with higher blood levels of certain types of PFAS had a greater risk of hypertension. Analyzing the annual follow-up visits of 1,058 midlife women who were initially free of hypertension from 1999 to 2017, the scientists found that 470 individuals developed this condition. The authors determined that women ages 45-56 who had high concentrations of PFOS in their blood had a 42 percent higher chance of developing high blood pressure, while those with high concentrations of PFOA had a 47 percent higher chance. Women who had high concentrations of all seven types of PFAS examined by the study had a 71 percent increased risk of getting high blood pressure.

Study author Ning Ding said PFAS exposure appears to put women at especially high risk in a broader way, as well.

“Women seem to be particularly vulnerable when exposed to these chemicals,” Ding, a postdoctoral fellow in the University of Michigan’s epidemiology department, said in a statement. “Exposure may be an underappreciated risk factor for women’s cardiovascular disease risk.”

Studies are also emerging that suggest links between PFAS and other health outcomes in girls or women, such as ADHD in girls or weight gain in women. Scientists have also linked PFAS exposure to an increased susceptibility of developing diabetes among middle-aged women. Some types of PFAS could disrupt the regulatory behavior of certain protein molecules and, in turn, raise the risk of diabetes within this cohort, according to the April 2022 study

Although the researchers stressed that evidence of sex-dependent links between PFAS and diabetes in humans is lacking, they pointed to another recent study showing that the metabolic responses of female mice to PFOA exposure were greater than those of male mice.

Meanwhile, another impact from PFAS has been shown to primarily affect boys. A 2022 study found that teen boys who are exposed to a mixture of the substances and another type of hormone-disrupting chemicals known as phthalates may have lower bone density — which makes bones weaker and more prone to fractures. 

Some vulnerabilities associated with PFAS may take root in utero. Prenatal exposure to the substances has been linked to preterm births, changes in birth weight or congenital issues that manifest later in childhood  — including ADHD or IQ effects, according to Birnbaum.

“We are seeing with PFAS — like a lot of chemicals which actually disturb hormone systems — that you do get a boy or girl difference,” she said, noting that some effects are appearing in only one sex.

“If you look at, say, baby boys and baby girls together, you might not see an effect. But if you separate out the sexes, all of a sudden you can see an effect in one of them,” Birnbaum added.

But she also acknowledged that not all researchers are open to that type of separation: “What’s interesting to me is that there are some people who don’t want to believe that. They think, well, if you don’t see it in both, you know, males and females, it can’t be happening.”

The discovery of sex-dependent health impacts often hinges upon what, exactly, scientists are looking for in their research, according to Birnbaum.

“It’s kind of the old story: If you don’t look, you don’t see. But when you start to look, you start to find.”