Feminizing Hormone Therapy in the Male Spontaneous Hypertensive Rat Impairs Accuracy of Estimated Renal Filtration

The biological effects of feminizing hormone therapy (FHT), 17β-estradiol (E2) with testosterone suppression, on renal filtration and injury in the male is unclear. The prevalence of hypertension, a major risk factor for renal disease, is 31% in men aged 18 to 39 years. Thus, this study tested the hypothesis that preexisting hypertension in the male who undergoes FHT heightens renal risk. Using the male spontaneous hypertensive rat (SHR), a well-characterized model of essential hypertension and renal injury, E2 (5 mg/kg, subcutaneously) was chronically administered starting at 19 weeks of age up to 32 weeks of age in the male SHR. Circulating E2 was significantly elevated; circulating testosterone and lean mass were significantly decreased in male E2-SHR compared to male controls. The 24-hour creatinine clearance was decreased, whereas serum creatinine was elevated in male E2-SHR; findings mimicked by cystatin C, a biomarker less influenced by muscle mass. Yet, 24-hour creatinine excretion and albuminuria adjusted to body weight or total lean mass did not differ, suggesting FHT in the male SHR is not associated with a reduction in renal filtration. Proteinuria was significantly reduced, but albuminuria, a more accurate marker for renal injury, was unchanged; NGAL and KIM-1 excretion and histological assessment were also unchanged in E2-SHR. To summarize, this study demonstrated that FHT in the hypertensive male was not associated with further impairment in renal filtration or worsened renal injury compared to control counterparts. However, FHT in males may affect the accuracy of biomarkers for estimation of renal filtration unless adjusted for lean mass.