Association between body mass index and sex hormones among men: Evidence from cross-sectional and Mendelian randomization studies

Purpose: This study aims to investigate the association between Body Mass Index (BMI) and sex hormone levels utilizing a cross-sectional study design alongside Mendelian randomization (MR) analysis. Materials and methods: A cross-sectional study was performed based on National Health and Nutrition Examination Survey (NHANES) 2013-2016. Additionally, a two-sample MR analysis was performed, utilizing Single Nucleotide Polymorphisms (SNPs) associated with BMI identified in a genome-wide association study (GWAS) comprising 339224 individuals. Data on outcomes, including total testosterone (TT, 199569 samples), estradiol (E-2, 17134 samples), and sex hormone binding globulin (SHBG, 185211 samples), were sourced from the United Kingdom Biobank (UKB). Results: In cross-sectional analysis involving 4092 males, multivariable linear regression demonstrated that each unit increase in BMI was positively correlated with an elevated risk of testosterone deficiency (TD), increased E-2 levels, and a reduced TT, SHBG, free androgen index and TT/E-2. Subsequent quartile division of BMI revealed, through multivariable logistic regression, that higher BMI quartiles were associated with a greater TD risk, elevated E-2 levels, and reduced TT, SHBG, and TT/E-2 levels compared to quartile 1 (P for trend <0.001). In the MR analysis, a causal effect was established, with each unit increase in BMI being associated with decreased TT (beta = -0.17; 95 % CI -0.24 to -0.09) and SHBG (beta = -0.13; 95 % CI -0.21 to -0.05) levels. Conclusions: Our findings unveil a causal link between BMI and reduced TT and SHBG levels in males.