Association between circulating sex hormone levels and diabetic kidney disease in men and postmenopausal women with type 2 diabetes mellitus

BACKGROUND Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease. The disease characteristics, morbidity, and renal function progression rate of patients with DKD are all related to sex. This suggests that sex hormones may play an important role in changing renal function in patients with diabetes. There have been only a few studies on the correlation between sex hormones and DKD, which have contradictory conclusions. AIM To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS This retrospective cross-sectional study included 356 patients with T2DM. Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices. By adjusting for age, body mass index, systolic blood pressure, diastolic blood pressure, duration of diabetes, use of sodium-glucose cotrasporter-2 inhibitor, use of glucagon-like peptide-1 receptor agonist, hypertension, use of angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, diabetic retinopathy, diabetic peripheral vascular disease, triglyceride, uric acid, and hemoglobin A1c, multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio (UACR) and DKD. RESULTS In men, dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors regression coefficient (β) = -0.691, 95% confidence interval (CI): -1.241 to -0.141 for quartile 4 vs quartile 1; P = 0.006 for trend. Elevated levels of estradiol were positively associated with DKD odds ratio (OR) = 3.097, 95%CI: 1.083-8.856 for quartile 4 vs quartile 1; P = 0.041 for trend, and higher luteinizing hormone (LH) levels were similarly associated with DKD (OR = 4.164, 95%CI: 1.30-13.330 for quartile 4 vs quartile 1; P = 0.048 for trend). In postmenopausal women, LH levels were positively correlated with log-transformed UACR and DKD (β = 1.039, 95%CI: 0.284-1.794 for quartile 4 vs quartile 1; P = 0.006 for trend and OR = 15.117, 95%CI: 2.191-104.326 for quartile 4 vs quartile 1; P = 0.004 for trend). Follicle-stimulating hormone (FSH) levels were also positively associated with DKD (OR = 9.588, 95%CI: 1.680-54.709 for quartile 4 vs quartile 1; P = 0.014 for trend). CONCLUSION In men with T2DM, elevated levels of estradiol and LH levels were positively associated with increased risk of DKD. In postmenopausal women with T2DM, high FSH and LH levels were positively associated with increased risk of DKD.