Chemical Exposures and Pubertal Timing: New Evidence in a Complex Area.

Around the world, girls on average are entering puberty earlier, and there’s evidence that boys, too, may be trending toward changes in pubertal timing.1,2 Rising childhood obesity rates likely play a role in the trend3—but what about exposure to endocrine-disrupting chemicals such as phthalates and bisphenol A (BPA)? Experimental studies have shown plenty of evidence that higher perinatal exposures to di(2-ethylhexyl) phthalate (DEHP)4,5 and BPA6,7 can indeed hasten puberty in female rodents. However, results from human studies have been mixed.8,9,10,11 A recent study reported in Environmental Health Perspectives adds to the mix of evidence, with the data in this case indicating delayed pubertal onset in girls and earlier onset in boys in association with phthalate and BPA exposures.12

The study was led by investigators at the University of California, Berkeley, Center for Environmental Research and Children’s Health (CERCH). It involved hundreds of pregnant mothers, most of them Latina, and later their children. The researchers measured urinary concentrations of eight phthalate metabolites in the women twice during pregnancy and assessed pubertal status in the children every nine months between the ages of 9 and 13 years.

Pubertal timing tends to run in families. Many other factors may play a role, too, including weight, exercise habits, and socioeconomic status.14 Image: © iStockphoto/Alex Potemkin.

After controlling for children’s overweight or obesity status and other factors, the investigators found an overall association between higher urinary concentrations of certain chemicals in mothers and later puberty in daughters. Estimated average differences were as high as 2–3 months for some biomarkers, depending on the measure of onset used. However, when the results were stratified by weight, most of the associations were stronger in girls with normal BMI than in girls who were overweight or obese. Among boys, on the other hand, higher maternal exposures were generally associated with earlier pubertal onset, and most of the associations with earlier onset were stronger in overweight or obese boys than in normal-weight boys.

Regarding this study and the evidence base overall, senior author and CERCH associate director Kim Harley says, “It is not as clean-cut a picture as we might have expected. But we’re still seeing pretty strong associations with timing of puberty, and that gives us cause for concern.” The timing of puberty has potential implications for health during development as well as later in life. For instance, some studies have reported an increased risk of breast cancer in women and testicular cancer in men associated with earlier and later puberty, respectively.13

There are several possible explanations for why the chemicals are associated with earlier puberty more consistently in rats than in humans, Harley explains. Perhaps these chemicals act differently in humans than they do in rats, or the animal model used in research is oversimplified. Perhaps the differences reflect uncontrolled confounding, the timing of when samples were taken, or the difficulty in accurately measuring exposures to these nonpersistent compounds. Alternatively, perhaps the chemicals themselves promote obesity, and the relationship between exposure and weight in terms of sexual development still needs to be better understood.

Mary Wolff, a professor of environmental medicine and public health at the Mount Sinai Icahn School of Medicine, suggests that although the study is founded on good biology, has a strong design, and should be commended for looking at prenatal exposures, it may be hampered by its modest population size (179 girls and 159 boys) and limited exposure range. “When you have small numbers and low concentration biomarkers, anything can happen,” says Wolff, who was not involved in the study.

These challenges are common, but a pooled analysis of all existing research in the field could help iron them out, Wolff says. “If you pool studies, you have a range of concentrations, and maybe you’d get a better-focused study,” she says. “There’s a lot of flip-flop [among the results of different studies]. Someone needs to make sense of that.”

Work is sorely needed in another, more difficult area, says John Meeker, a professor of environmental health sciences at the University of Michigan, who also was not involved in the study. That area involves evaluating the combined effects on pubertal timing of exposure to endocrine disruptors found not only in plastics, foods, and consumer products, but also in pesticides and flame retardants. “That’s where the field is moving,” Meeker says. “[Toward] how to best look at mixtures, and how to do it efficiently with the sample sizes that we see with these long-term cohorts.”