“Forever chemicals” a culprit in delayed puberty in girls

Exposure to per- and polyfluoroalkyl substances (PFAS), dubbed “forever chemicals,” may contribute to a delay in puberty through its effects on body mass index (BMI) and sex hormones, as shown in a study.

In a US cohort of 704 6-to-8-year-old girls, increasing serum concentrations of perfluorooctanoic acid (PFOA)—one of the most well-studied PFAS—was associated with a delay in the appearance of pubic hair (pubarche: hazard ratio [HR], 0.83, 95 percent confidence interval [CI], 0.70–0.99) and in the first occurrence of menstruation (menarche: HR, 0.04, 95 percent CI, 0.01–0.25). [Environ Health Perspect 2023;doi:10.1289/EHP11811]

Structural equation models showed a triangular relationship between PFOA, BMI percentile, and the age at the pubertal milestone, such that increased PFOA concentrations were predictive of lower BMI and later pubertal milestones, whereas higher BMI predicted earlier pubertal milestones.

Other PFAS such as perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) were associated with a delay in breast development or later thelarche, with Me-PFOSA-AcOH also showing association with later pubarche.

Of note, PFOA was inversely associated with DHEAS (p<0.01), estrone (p=0.04), and testosterone (p=0.03) concentrations at 6 months prior to puberty.

These PFOA-associated decreases in sex hormone concentrations represent biological biomarkers of effect consistent with the delay in onset of puberty, according to the investigators led by Dr Susan Pinney from the University of Cincinnati College of Medicine, Cincinnati, Ohio, US.

“In girls with PFAS exposure, puberty is delayed 5 or 6 months on average, but there will be some girls where it’s delayed a lot more and others where it wasn’t delayed at all. We are especially concerned about the girls at the top end of the spectrum where it's delayed more,” Pinney said.

“Puberty is a window of susceptibility. Environmental exposures during puberty, not just to PFAS, but anything, have more of a potential for a long-term health effect. What these [exposures] have done is extended the window of susceptibility, and it makes [the girls] more vulnerable for a longer period of time,” she added.

Pinney stressed that the long-term follow-up of the girls, including their reproductive hormone levels as adults in both the follicular and luteal phases of the menstrual cycle and their pregnancy outcomes, should provide additional insight into the effects of PFAS, as a disrupted endocrine environment early in life can affect reproductive health in adulthood. [Ann Oncol 2011;22:1102-108]

PFAS in Greater Cincinnati

The analysis was based data from 353 girls in the Greater Cincinnati (GC) area and 351 girls in the San Francisco Bay Area (SFBA). The mean age at thelarche and pubarche was 9.3 and 9.9 years, respectively. The average age at menarche was 12.3 years, with 81.7 percent of the girls having had their first menstruation by the end of study follow-up.

Median concentrations of PFOA significantly differed by study site: 7.3 ng/mL in GC and 5.8 ng/mL in SFBA. Notably, the PFOA serum concentrations exceeded the National Health and Nutrition Examination Survey 2005–2006 95th percentile value for children 12–19 years of age in 38.6 percent of the girls in GC and in 14 percent of the girls in SFBA.

Pinney pointed out that the higher PFAS exposure in Greater Cincinnati than in San Francisco Bay Area may be attributed to a variety of factors. Greater Cincinnati gets its supply of drinking water mainly from the Ohio River, into which a DuPont plant in Parkersburg, West Virginia, released PFAS for decades. The chemicals then flowed downstream to major water intakes on both sides of the river in eastern Hamilton County. Aside from this, firefighting foam, which contains PFAS, is used at a nearby training ground, which could contaminate the water intakes.

The present study adds to the evidence that PFAS can cause a number of serious health problems. Pinney highlighted the failure of the US to follow the precautionary principle, where steps should have been taken to reduce exposure to PFAS even if all the ways that such chemicals can harm the human body are not fully understood.

“The evidence of PFAS being dangerous goes all the way back to the 1980s when chemists were doing studies, noticed that PFAS had the same chemical structure as other dangerous chemicals and they reported on it,” Pinney said. “It’s taken a very long time for us to recognize it as a human toxin. Meanwhile, all of these toxins got into our environment, and it's going to take a long time before they leave.”