What is the clinical evidence from this study?

Study design: Other. Population: Aging and feminizing hormone therapy. Intervention: 17β-estradiol (E2) supplementation plus castration (CTX) vs. Control. Primary outcome: Renal function, renal injury, and activation of the renin angiotensin system.

May 21, 2026

Chronic estrogen supplementation in the aging castrated male rat is not associated with renal injury or activation of the renin angiotensin system

Key Result

Feminizing hormone therapy with 17β-estradiol and castration in aging male rats reduced proteinuria and glomerular injury without increasing inappropriate activation of the renin angiotensin system.

Key Points

The study aimed to determine the effects of chronic estrogen supplementation on renal function and injury in aging male rats.
Experimental model using 17β-estradiol supplementation and castration in male Sprague Dawley rats aged 13-15 months.
Assessment of renal function through creatinine excretion, clearance, and biomarkers over a 9-month period.
Comparison of renal injury markers and RAS activation between control and estrogen-treated groups.
No significant difference in 24-hour creatinine excretion or creatinine clearance between E2+CTX and control groups.
Proteinuria and urinary KIM-1 were significantly reduced in E2+CTX compared to control, indicating less renal injury.
Renal angiotensinogen mRNA expression decreased in E2+CTX, suggesting no activation of the renin angiotensin system.

Structured PICO

Does 17β-estradiol supplementation plus castration impair renal function and cause renal injury in aging male rats?

Population

Male Sprague Dawley rats starting at 13-15 months of age

Intervention

17β-estradiol (E2) (5 mg/kg, s.c.) supplementation plus castration (CTX) for 9 months

Comparator

Control rats

Outcome

Renal function and renal injury associated with activation of the renin angiotensin system (RAS)surrogate

Chronic estrogen supplementation and castration in aging male rats is not associated with increased renal injury or inappropriate activation of the renin-angiotensin system.

Limitations

Whether renal function is altered remains unclear

Abstract

The biological effects of chronic estrogen supplementation on renal function and injury with aging in men are unknown. Using an experimental model of feminizing hormone therapy (FHT) induced by 17β-estradiol (E2) (5 mg/kg, s.c.) supplementation plus castration (CTX) in the male Sprague Dawley rat starting at 13-15 months of age, equivalent to a late thirty- to forty-year-old man, we tested the hypothesis that FHT is associated with impaired renal function and renal injury with aging associated with activation of the renin angiotensin system (RAS). However, 24-hour creatinine excretion, plasma creatinine, and creatinine clearance did not differ in E2+CTX compared to Control by 22-24 months of age, or following 9 months of FHT. Lean mass was significantly reduced in E2+CTX versus Control, but creatinine clearance adjusted to lean mass did not differ. Serum cystatin C, a more reliable biomarker for renal function, was unchanged; urinary cystatin C was reduced, suggesting no renal impairment. However, cystatin C clearance was reduced in E2+CTX versus Control, suggesting decreased renal filtration. Proteinuria, urinary KIM-1 (a marker of proximal tubule injury), and glomerular injury score were significantly reduced in E2+CTX versus Control; however, albuminuria did not differ. Renal angiotensinogen mRNA expression was significantly decreased in E2+CTX, whereas urinary angiotensinogen, renal renin, and renal angiotensin type 1 receptor mRNA expression did not differ. Collectively, these results suggest that the biological effects of FHT in the aging male are not associated with increased renal injury or inappropriate activation of the RAS; whether renal function is altered remains unclear.

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