Abstract 072: Medroxyprogesterone Prevents the Decline in Renal Health Due to Estradiol

Abstract

We previously published that estradiol (E2) treatment initiated immediately after midlife ovariectomy (OVX) for 80 days in female Long Evans rats exerted negative effects on renal health. Medroxyprogesterone (MPA) is a progesterone derivative commonly used in menopausal hormone therapy to oppose the uterotrophic effects of E2. Therefore, our goal was to determine if coadministration with MPA opposed the negative effects of E2 on renal health. Female retired breeders underwent OVX at 11 months of age and received an implant of E2, E2+MPA or vehicle for 40 days. Body weights, blood pressure and urine were measured pre- and post-treatment along with tissue weights. Systolic blood pressure was not altered from baseline in any treatment group (Veh: 144±4 vs.135±5; E2: 143±4 vs.143±6; E2+MPA: 147±4 vs.143±5 mmHg; ns). Kidney hypertrophy was significantly increased following E2+MPA treatment (Veh: 2.73±0.1; E2: 3.03±0.9; E2+MPA: 3.42±0.2 g/kg body wt; P=0.002), while body and heart weights were comparable between groups. Coadministration of MPA prevented the E2-induced increase in proteinuria (Veh: 0.27±0.07; E2: 3.53±1.16; E2+MPA: 1.20±0.58 mg/mg creatinine; P=0.01) and decline in glomerular filtration rate (Veh: 0.51±0.02; E2: 0.24±0.05; E2+MPA: 0.39±0.05 ml/min; P=0.001). Our results show that even short-term E2 exerts a negative effect on renal health in midlife, but coadministration with MPA prevents E2-mediated damage, possibly via compensatory hypertrophy of the kidney. Therefore, midlife hormone therapy containing MPA may protect the kidneys against unopposed E2-mediated damage and provide a beneficial effect for menopausal women.