Endogenous sex steroid hormones and measures of chronic kidney disease (CKD) in a nationally representative sample of men

Abstract

Context Sex steroid hormones may play a role in the pathogenesis of chronic kidney disease (CKD). Objective To determine whether sex steroid hormone concentrations are associated with kidney function or kidney damage in men in the general US population. We hypothesized that lower serum testosterone and E₂ concentrations are associated with CKD. Design patients and measurements Serum sex steroid hormones were measured by electrochemiluminescence immunoassays for 1470 men who attended the morning session of Phase I of the Third National Health and Nutrition Examination Survey (NHANES III). We used two measures of CKD, estimated glomerular filtration rate (eGFR) < 60 ml/min/1·73 m² calculated using serum creatinine or cystatin C levels and the abbreviated Modification of Diet in Renal Disease Study formulae and urinary albumin : creatinine ratio (UACR) ≥ 17 mg/g. Results Mean free testosterone concentration was higher in men with an eGFR < 60 ml/min/1·73 m² than in men with a higher eGFR. In multivariable adjusted models, the odds of an eGFR < 60 ml/min/1·73 m² or UACR ≥ 17 mg/g did not differ across tertiles of hormones with the exception of free E₂; those in the highest vs. lowest tertile had an elevated odds of decreased eGFR (OR: 3·04, 95% CI (1·22, 7·57); P-trend = 0·02). Conclusions In a nationally representative sample of US adult men, higher free E₂ concentration was significantly associated with an eGFR < 60 ml/min/1·73 m² as assessed by serum creatinine or cystatin C even after multivariable adjustment. These findings are in contrast to the hypothesis that oestrogens may protect against CKD, though reverse causation cannot be ruled out. Longitudinal investigation of the role of oestrogens in kidney haemodynamics, function, and pathophysiology is warranted.