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

Area of Science:

• Endocrinology
• Nephrology
• Public Health

Background:

• Chronic kidney disease (CKD) often co-occurs with hormonal imbalances.
• The precise relationship between kidney function and testosterone levels is not fully understood.

Purpose of the Study:

• To investigate the association between estimated glomerular filtration rate (eGFR) and total testosterone levels.
• To determine the exposure-response curve for testosterone in relation to CKD risk and eGFR.
• To validate findings in a kidney transplant recipient cohort.

Main Methods:

• Analysis of National Health and Nutrition Examination Survey (NHANES) and UK Biobank (UKBB) data.
• Multivariate logistic and linear regression models were employed.
• Restricted cubic splines (RCS) were used to visualize nonlinear relationships.
• Kidney transplant recipients served as a validation cohort.

Main Results:

• A linear association was observed between lower eGFR and lower total testosterone.
• A nonlinear, threshold-like pattern emerged, with CKD risk increasing steeply below testosterone levels of 300-400 ng/dL.
• CKD was associated with reduced testosterone levels, but not estradiol.
• Total testosterone levels significantly increased post-kidney transplantation.

Conclusions:

• A linear-threshold relationship exists between declining eGFR and reduced testosterone.
• Testosterone levels significantly improve following recovery of renal function.