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

ABSTRACT

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 (E2, 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 E2 levels, and a reduced TT, SHBG, free androgen index and TT/E2. Subsequent quartile division of BMI revealed, through multivariable logistic regression, that higher BMI quartiles were associated with a greater TD risk, elevated E2 levels, and reduced TT, SHBG, and TT/E2 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 (ß = -0.17; 95 % CI -0.24 to -0.09) and SHBG (ß = -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.