ESPE Abstracts (2019) 92 P1-260

A Case-Control Study of Exposure to Bisphenol-A and Phthalates in Girls with Early Onset of Puberty

Annalisa Deodati1,2, Giorgia Bottaro1, Cinzia La Rocca3, Sabrina Tait3, Francesca Maranghi3, Roberta Tassinari3, Luca Busani3, Fabrizia Carli4, Veronica Della Latta4, Emma Buzzigoli4, Amalia Gastaldelli4, Stefano Cianfarani1,2,5

1Bambino Gesù Children's Hospital, DPUO, Endocrinology Unit, rome, Italy. 2Tor Vergata University, rome, Italy. 3National Institute of Health, rome, Italy. 4Institute of Clinical Physiology, CNR, Pisa, Italy. 5Department of Women's and Children's Health, Karolinska Institutet, stockolm, Sweden

Background: Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. Several factors including genetic predisposition, psychosocial and socio-economic conditions, diet and ethnicity may have contributed to this phenomenon. Epidemiological and animal studies have shown that the exposure to BPA and DEHP may be associated with early onset of puberty in girls.

Objective: To investigate the association between the exposure to BPA, DEHP's metabolites in girls with idiopathic premature thelarche (IPT) or idiopathic central precocious puberty (ICPP).

Methods: A case-control study was conducted in 97 girls, subdivided into 3 groups: 31 with ICPP (mean age 7.3±0.07), 39 with IPT (mean age 6.56 ± 1.6) and 27 controls (mean age 6.67± 2.3).

Urine BPA and DEHP metabolites were measured by gas chromatography and high-performance liquid chromatography (LC–MS/MS). Metabolic and hormone levels were assessed. Individual environmental exposure was evaluated through "ad hoc" questionnaires providing data on life styles, diet and other potential determinants of exposure.

Results: Our findings showed the presence of measurable concentrations of the EDCs in all girls, including the control group. These data demonstrate the widespread exposure to these compounds. ICPP and IPT girls showed no significantly difference in EDCs levels neither compared to controls nor compared to each other. In IPT group, a significant positive correlation between DEHP levels and FSH peak was found, suggesting that phthalates could potentially cause self-limited breast development without progression to true ICPP (P<0.05). Furthermore, in IPT group significant negative correlations were found between DEHP metabolites, KISS serum levels and AMH hormone (r= -0.4, P= 0.01; r= -0.37, P= 0.02, respectively). Since no significant difference in the exposure was found between cases and controls, we considered that the association between life style data derived from questionnaires and exposure corresponded to data from general pediatric population. Briefly, higher levels of phthalates were associated with: i) use of disposable plastic; ii) use of plastic containers in microwave; iii) playing many hours a day with plastic toys including electronic toys. The use of disposable plastic was also associated with higher levels of BPA.

Conclusions: Our findings suggest that concentrations of urine BPA and DEHP's metabolites are measurable in all girls. The use of plastic exposes girls to a higher contamination from both BPA and DEHP. These results warrant further experimental and prospective clinical investigations to clarify the potential role of EDCs in modulating the timing of puberty in girls.