Lower eGFR Associated With Decreased Total Testosterone in Males: Integrated Evidence From Cohorts to Real‐World Data

ABSTRACT Background Chronic kidney disease (CKD) frequently coexists with hypothalamic–pituitary–gonadal dysfunction, yet the exposure–response shape linking kidney function, testosterone, and outcomes remains unclear. Methods Based on data from five cycles of the National Health and Nutrition Examination Survey (NHANES) and the UK Biobank (UKBB), we used multivariate logistic regression models and linear regression models to explore the associations between total testosterone levels and CKD as well as estimated glomerular filtration rate (eGFR). Subsequently, we plotted restricted cubic splines (RCS) of testosterone levels against the risk of CKD and the eGFR. Finally, we further verified the association between total testosterone levels and eGFR based on the kidney transplant cohort. Results Across both populations, lower eGFR was revealed to be associated with lower total testosterone in an approximately linear fashion. RCS identified an inflection around the “borderline low” range of about 300–400 ng/dL; below that, CKD risk rose steeply, indicating a nonlinear, threshold‐like risk pattern. The logistic regression analysis based on the public databases also indicated that CKD would reduce testosterone levels (NHANES: β = −17.98, 95% CI: −29.54, −6.420, p ‐value = 3.4 × 10 −3 ; UKBB: β = −12.25, 95% CI: −14.84, −9.661, p ‐value = 1.9 × 10 −20 ), but it had no effect on estradiol. In the validation cohort of kidney transplant recipients, total testosterone increased significantly after transplantation, whereas estradiol showed no parallel rise. Conclusion Our findings demonstrate a clear linear–threshold relationship between declining eGFR and reduced testosterone levels, and show that testosterone significantly increases after renal function recovery in kidney transplant recipients.