Cheng Guan, Wen Jiahui, Zhang Feng, Qu Rui, Deng Zhimin, Dai Fangfang, Xiao Yanfei, Dai Mengyang, Yin Tailang, Yan Jie, Zhang Yan
Department of Clinical Laboratory, institute of translational medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
Reprod Toxicol. 2025 Oct;137:109023. doi: 10.1016/j.reprotox.2025.109023. Epub 2025 Aug 6.
Brominated flame retardants (BFRs) are endocrine-disrupting contaminants; however, the impact of BFR mixtures on sex steroid hormone levels in adults remains unclear.
This study included 2513 male and female adults from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Weighted linear regression was employed to examine the associations between individual BFR exposures and total testosterone(TT), estradiol(E2), sex hormone binding globulin (SHBG), free androgen index (FAI), and TT/E2. The generalized additive model (GAM) was used to explore the nonlinear associations between BFRs and sex steroid hormones. Additionally, weighted quantile sum (WQS) regression and Quantile G-computation (QGC) were applied to evaluate the overall effects of BFRs mixtures on these five sex hormone biomarkers and to identify key contributing chemicals. We also explored potential effect modifications by age, BMI and educational level.
The weighted linear regression results indicated that, after adjusting for covariates, PBDE209 was significantly negatively associated with SHBG in males (β = -8.495, 95 % CI: -15.915, -1.073), while PBB153 and PBDE85 were negatively associated with female TT/E2 (β = -0.718, 95 % CI: -1.362, -0.075) and E2 (β = -2.910, 95 % CI: -5.126, -0.693), respectively. The Generalized Additive Model (GAM) revealed nonlinear associations between certain BFRs and TT, E2, FAI, and TT/E2 in both males and females. WQS regression analysis showed a significant negative association between the WQS index and male SHBG (β = -1.919, 95 % CI: -3.706, -0.133), which was consistent with the results from the weighted linear regression. However, no significant associations were observed between mixed BFR exposure and female sex hormone levels. Further confirmation of the WQS regression findings was provided by QGC analysis. Notably, PBDE209 was identified as the primary BFR influencing SHBG levels.
Exposure to mixed BFRs significantly affects SHBG levels in adult males, while no significant impact on sex steroid hormone levels was observed in adult females. Further studies are required to evaluate the potential long-term health consequences.
