Perfluorooctanoic acid (PFOA) and Pubertal Maturation in Young Girls

Susan M. Pinney 1, Gayle C. Windham2, Frank M. Biro3 ,4, Larry H. Kushi5, Lusine Yaghjyan1, Antonia Calafat6, Kayoko Kato6, Paul Succop1, M. Kathryn Brown1, Ann Hernick1, Robert Bornschein1
1University of Cincinnati College of Medicine, Dept. of Environmental Health, Cincinnati, OH, USA, 2Environmental Health Investigation Branch, California Department of Public Health, Richmond, CA, USA, 3University of Cincinnati College of Medicine, Dept. of Pediatrics, Cincinnati, OH, USA, 4Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, 5Division of Research, Kaiser Permanente, Oakland, CA, USA, 6Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA

Background: Polyfluoroalkyl compounds (PFCs) and their salts, such as perfluorooctanoic acid (PFOA), have been reported to change mammary gland structure and function in laboratory animals. We explored the relationship between serum PFOA concentration and timing of pubertal maturation in young girls.

Methods: Within the NIH Breast Cancer and the Environment Research Centers (BCERC), we conducted a study of multiple environmental biomarkers, including PFOA and other PFCs in serum of young girls (age 6-7 years at entry) from two sites (N=689 girls). Pubertal staging (breast (B) and pubic hair (PH)) has been conducted by clinicians or trained research staff, every year or more frequently, for as long as four years.  After calculating adjusted geometric means for all PFCs, we examined the relationship between PFOA serum concentration at the beginning of the study with body mass index (BMI) and pubertal Stage 2 at baseline and one year follow-up. 

Results:  Detectable serum levels of five PFCs, including PFOA, were found in >95% of the girls.   The PFOA median was 6.4 ng/ml (range < LOD 0.1 to 55.9 ng/ml), with 24.9% having values above the 95th percentile for children 12-19 years (NHANES 2003-2004 population (8.6 ng/ml)).  At the follow-up visit, 28.3% of girls had reached Tanner stage B2+, 19.2% were PH2+ and 30.3% had a BMI percentile for age >85. In analyses where serum PFOA was modeled as a continuous variable, we found a direct relationship with pubertal breast status and an inverse relationship with BMI percentile at the follow-up visit, with adjustment for age, race, site and caregiver education. 

Conclusions: It appears that PFOA acts as an endocrine disruptor although perhaps not by the usual mechanism. Although the relationship with BMI was inverse, there was a direct relationship with breast maturation.  We continue to explore these complex relationships in models including other covariates.