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

Abstract

Objective To determine whether hormone replacement therapy can reverse established renal microvascular damage in type 2 diabetes and hypertension.Design Prospective, single centre clinical trial.Setting Outpatient clinics. ParticipantsMethods Administration of a cyclic combination of oestradiol and norgestrel orally for 3.5 monthly cycles. ResultsComparing the baseline values, mean (SD) 24-hour urine protein excretion was reduced from 0.452 g (0-039) to 0.370 g (0-047) (P c 0.01) and creatinine clearance was increased from 1-68 d s e c (0.11) to 1.77 d s e c (0-08) (P < 0.05). Fasting plasma glucose also improved from 6.92 mmoVL (0.47) to 6.51 mmoVL (0.28) ( P c 0.05), as did serum total cholesterol from 7.26 mmol/L (0.28) to 6.65 mmoVL (0.14) (P < 0.05). Blood pressure did not change significantly.Univariate linear regression analysis showed no significant correlation between the individual changes in blood pressure, fasting plasma glucose or serum cholesterol and the individual changes in proteinuria or creatinine clearance.Conclusions This study shows that hormone replacement therapy may reduce proteinuria, and even improve creatinine clearance, in diabetic and hypertensive postmenopausal women. These effects are additive to nephroprotective therapy, and the mechanisms appear unrelated to conventional risk factors for vascular complications, such as high blood pressure, elevated plasma glucose or serum cholesterol.Sixteen diabetic and hypertensive postmenopausal women (age 47-57 years)

Estrogens and the diabetic kidney

“…These observations imply an association between onset of sexual maturity and the development and progression of diabetic nephropathy. Short-term administration of estrogen alone 55,56 or together with norgestrel (a synthetic progestin) was found to reduce proteinuria and improve creatinine clearance in diabetic and hypertensive postmenopausal women. 57 Short-term treatment with raloxifene limits the progression of albuminuria in postmenopausal women with type 2 DM.…”

The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats

“…14,15 According to this data, short-term administration of estrogen was found to improve proteinuria and creatinine clearance in diabetic and hypertensive postmenopausal women. 16 Another study supports the beneficial effect of estrogens on insulin action, which was demonstrated to be greater in premenopausal women. 17,18 In this study, an animal model of ovariectomy with sepsis and diabetes was used to investigate the effects on immunologic response, mortality, and tissue oxidant status.…”

Effects of Estrogen Replacement Therapy to the Renal Function in Postmenopausal Women

“…Vasküler sistemle iliflkili olan renal mikrovasküler sistem üzerine s›n›rl› bilgi olup, özellikle cerrahi menopoz sonras› östrojen eksikli¤inin veya farmakolojik dozlarda östrojen replasman tedavisinin (ERT) bu sistem üzerine etkisi tam olarak bilinmemektedir (25) .…”

“…Hiperkolesterolemik ‹mai ratlarda yap›lan çal›flmaya ters olarak obez Zucker ratlarda ise anormal proteinürinin, ooferektomi sonras› normale döndü¤ü gösterilmifltir (24) . (25) .…”