Abstract
Osteoporosis and osteoporosis-related fractures exhibits a higher prevalence among females, particularly those aged 50 and above, implying a potential association between sex hormones and bone mineral density (BMD). However, the precise role of sex hormones in BMD remains elusive. Meanwhile, estradiol-to-testosterone ratio (E(2)/T ratio) or testosterone-to-estradiol ratio (T/E(2) ratio) is a new biomarker of sex hormone milieu. We investigated whether sex hormones, E(2)/T ratio and T/E(2) ratio were associated with BMD or fractures risk in US females. This study is a cross-sectional study, and the data sourced from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 cycle. This study primarily focuses on females aged 50 and above, employing weighted multivariate linear regression, restricted cubic spline (RCS) model to examine the association between sex hormones and BMD or FRAX scores. We included 1,012 females. Testosterone was not associated with BMD or fracture risk. Increasing estradiol and E(2)/T ratio were positively correlated with BMD and negatively correlated with osteoporosis-related fractures risk, while increasing T/E(2) ratio was negatively correlated with BMD and increased risk of osteoporosis-related fractures. The T/E(2) ratio showed better specificity for predicting low BMD compared to estradiol alone. These findings suggest that hormonal ratios can serve as predictive biomarkers for osteoporosis and fractures. This study highlights the potential of E(2)/T and T/E(2) ratios as biomarkers for assessing osteoporosis risk in postmenopausal women. Incorporating these ratios into clinical practice could improve early diagnosis and risk stratification for osteoporosis-related fractures. Future longitudinal studies are needed to confirm these findings and further explore the causal relationships between sex hormones and bone health.