Phthalate exposure among US women, NHANES 1999--2002: Relationship to serum gonadotropin levels

Phthalates are industrial chemicals used primarily as plasticizers though they and are found in a myriad of consumer goods such as children's toys, food packaging, dental sealants, cosmetics, pharmaceuticals, perfumes, and building materials. US biomonitoring data show more than 75% of the population have exposure to mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl) hexyl phthalate (MEHP), and mono-benzyl phthalate (MBZP). Reproductive toxicity from phthalate exposure in animal models has raised concerns about similar effects on fertility in humans. This dissertation research focuses on phthalate exposures in the US population and investigates the plausibility of an exposure-response relationship between phthalates and endocrine hormones essential for ovulation among US women. The objective of this research is to determine the relationship between levels of gonadotropins, follicle stimulating hormone (FSH) and leutinizing hormone (LH), and urinary phthalate monoester metabolites: MBP, MEP, MEHP, MBZP among National Health and Nutrition Examination Survey (NHANES) 1999-2002 women aged 35 to 60 years. Using biomarker data from a one-third sub-sample of NHANES participants, log transformed serum FSH and serum LH, respectively were regressed on phthalates controlling for age, body mass index, smoking, and creatinine taking into consideration the complex survey design (n=385). Models were stratified by reproductive status: reproductive (n=185), menopause transition (n=49) and post-menopausal (n=125). A decrease in FSH associated with increasing MBzP (beta=-0.094, p<0.05) was observed for all participants but no statistical association between log FSH and MBP, MEP, or MEHP was seen. A decrease in LH (beta=-0.125, p<0.05) was also observed with increasing MBzP for all participants though there was no relationship between levels of LH and MBP, MEP, or MEHP. The observed associations between FSH, LH and MBzP did not persist when stratified by reproductive status. Thus, the present study shows a change in endocrine hormones related to ovulation with increasing urinary MBzP among a representative sample of US women from 1999-2002 though this observed exposure-response relationship does not remain after stratification by reproductive status. ^