Unveiling mechanisms underlying kidney function changes during sex hormone therapy.

Summary

Feminizing therapy increased mGFR and renal perfusion while reducing tubular injury markers without raising glomerular pressure. Masculinizing therapy was associated with elevations in urine YKL-40 and plasma TNFR-1. Proteomics highlighted estradiol-associated kidney-protective proteins and testosterone-associated opposing profiles, supporting sex-specific renal physiology.

Key Findings

• Feminizing therapy increased mGFR by +3.6% and renal perfusion by +9.1% (P < 0.05) without increasing glomerular pressure.
• Tubular injury biomarkers (urine NGAL, EGF, MCP-1, YKL-40) decreased by 42–58% during feminizing therapy.
• Masculinizing therapy showed stable mGFR/perfusion but increased urine YKL-40 (+134%) and plasma TNFR-1 (+8%).
• Proteomics identified 49 vs 356 differentially expressed proteins in feminizing vs masculinizing therapy, with estradiol positively associated with kidney-protective proteins (e.g., SFRP4, SOD3, TSG-6, agrin).

Clinical Implications

Monitor renal function and tubular injury biomarkers during sex hormone therapy; estradiol appears renoprotective whereas testosterone may increase injury-related signals, suggesting tailored monitoring and risk mitigation strategies.

Limitations

• Small sample size (n=44) and short follow-up (3 months) limit long-term inference.
• Observational design with potential residual confounding (e.g., antiandrogen types, dosing heterogeneity).

Future Directions

Longer-term, larger cohorts to assess renal outcomes and dose–response; interventional studies testing hormone modulation or adjunct renoprotective strategies.