April 01, 2017

ORLANDO, Florida — The first evidence that environmental exposure to commonly used pesticides — the pyrethroids — at levels that are actually present in humans is likely speeding up puberty in boys has been reported.

Jing Liu, PhD, of Zhejiang University, Hangzhou, China, and colleagues assessed pyrethroid metabolites in the urine of more than 400 Chinese boys aged 9 to 16 and demonstrated that those who had a 10% increase in such metabolites were 100% to 200% more likely to be in an advanced stage of puberty.

They also verified the mechanisms that might be causing this with additional experiments in mice.

Pyrethroids account for about 30% of global insecticide usage, Dr Liu told reporters in a press briefing on endocrine-disrupting chemicals here at ENDO 2017: The Endocrine Society Annual Meeting.

"Residues of this pesticide are often found in vegetables, in milk, and in baby food," she said, and they are also found in the indoor environment generally. So "humans are exposed to this pesticide," she stressed, noting that residues have been found in the urine of >60% of children in China, the United States, and other countries.

Concurrently, while it has been known for some time, from about the late 1990s, that there is a trend whereby girls are going through puberty earlier, it has only more recently become apparent that the same phenomenon is occurring in boys, she noted.

This is important because boys who go through puberty at a younger age have an increased risk of testicular cancer and depression compared with their peers who mature at a later age, she explained.

"Given the growing use of pyrethroid insecticides, our findings have important implications for the assessment of children's health risk from these insecticides…[and] suggest pyrethroid exposure is a potential risk factor for earlier male puberty."

Asked to comment on what could be done about endocrine-disrupting chemicals in general, doctors and scientists at the briefing told the media that it is first important for doctors and the public "to understand what additional causative actions are at play" when it comes to these ubiquitous chemicals.

Therefore, much more research is needed to investigate how these chemicals are exerting their many effects and to establish associations, said Julie Ann Sosa, MD, an endocrine surgeon and surgical oncologist from Duke University Medical Center, Durham, North Carolina.

"We need to understand that 'progress' potentially comes with a cost," Dr Sosa said, emphasizing that doctors and researchers must become advocates. "If we understand the cons, we can start to work on alternatives [that are safer]," she emphasized.

Highly Significant and Positive Link Between Pyrethroids and Puberty

Dr Liu told reporters that while the WHO has recognized that many endocrine-disrupting chemicals may affect the onset of human puberty, there are few data on pyrethroid exposure and puberty, and the mechanisms by which pyrethroids may do this "remain poorly understood."

Also, much of the prior research done on endocrine-disrupting chemicals and puberty has focused on girls rather than boys.

In their study, she and her colleagues recruited 463 boys aged 9 to 16 from a cross-sectional study in Hangzhou, China. They analyzed 3-phenoxybenzoic acid (3-PBA) — a common metabolite of pyrethroids — in the urine of the boys and recorded Tanner Stage of puberty via assessment of genitalia development and testicular volume.

A 10% increase in 3-PBA was associated with an approximate 3% increase in the boys' levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). And having anincreased urinary level of 3-BPA raised the odds of a boy being at an advanced stage of puberty by 113% to 268%

"For the first time, to our knowledge, this work reveals a highly significant and positive association between pyrethroid exposure and gonadotrophin levels in 463 Chinese boys (P < .001)," she and her colleagues explain, and an increase in 3-BPA in the urine was "associated with a significantly increased risk of earlier pubertal onset."

They then went on to study the mechanism that might be behind these effects in mice, both in vitro and in vivo, because, as Dr Liu noted, it is difficult to test the direct causality of environmental risk factors in humans.

"Consistent with the human data, our animal study shows that postnatal exposure to a widely used pyrethroid pesticide, cypermethrin, can accelerate pubertal timing and induce circulating levels of gonadotrophins and testosterone in male mice," she explained.

Indeed, their murine research revealed some potential new mechanisms by which pyrethroids could be affecting pubertal onset, including, for example, increasing testosterone synthesis through activation of certain pathways in the Leydig cells of the testes, she noted.

"This is the first study to provide evidence that environmental exposure to pyrethroids…is associated with measurable effects on male pubertal development. Given the growing use of pyrethroid insecticides, we must prudently assess these chemicals for their risks to children's health," she concluded.

Dr Liu reported no relevant financial relationships.  

ENDO 2017. April 1, 2017; Orlando, Florida. Abstract OR 15-5

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