Postmenopausal hormone replacement improves proteinuria and impaired creatinine clearance in type 2 diabetes mellitus and hypertension

Objective To determine whether hormone replacement therapy can reverse esta blished renal microvascular damage in type 2 diabetes and hypertension. Design Prospective, single centre clinical. trial. Setting Outpatient clinics. Participants Sixteen diabetic and hypertensive postmenopausal women (age 47 -57 years) Methods Administration of a cyclic combination of oestradiol and norgestrel orally for 3.5 monthly cycles. Results Comparing the baseline values, mean (SD) 24-hour urine protein excr etion was reduced from 0.452 g (0.039) to 0.370 g (0. 047) (P < 0.01) and c reatinine clearance was increased from 1/6 mL/sec (0.11) to 1.77 ml/sec (0. 08) (P < 0.05). Fasting plasma glucose also improved from 6.92 mmol/L (0.47 ) to 6.51 mmol/L (0.28) (P < 0.05), as did serum total cholesterol from 7.2 6 mmol/L (0.28) to 6.65 mmol/L (0.14) (P < 0.05). Blood pressure did not ch ange significantly. Univariate linear regression analysis showed no signifi cant correlation between the individual changes in blood pressure, fasting plasma glucose or serum cholesterol and the individual changes in proteinur ia or creatinine clearance. Conclusions This study shows that hormone replacement therapy may reduce pr oteinuria, and even improve creatinine clearance, in diabetic and hypertens ive postmenopausal women. These effects are additive to nephroprotective th erapy, and the mechanisms appear unrelated to conventional risk factors for vascular complications, such as high blood pressure, elevated plasma gluco se or serum cholesterol.