Effects of gender affirming hormonal therapy with testosterone on renal function of assigned female at birth transgender people: a meta-analysis

Daniele Tienforti^1*Luca Spagnolo¹Luca Piscitani²Camilla Tonni¹Vittoria Donatelli¹Giuliana Cordeschi¹Marco Giorgio Baroni¹Arcangelo Barbonetti¹

• ¹University of L'Aquila, L'Aquila, Italy
• ²ASL 1 Avezzano Sulmona L'Aquila, L'Aquila, Abruzzo, Italy

Objective:The impact of testosterone-based gender affirming hormone therapy (T-GAHT) on kidney function in transgender individuals assigned female at birth (AFAB) remains uncertain. This study aimed to evaluate, through a meta-analytical approach, changes in estimated glomerular filtration rate (eGFR)—a clinical parameter reflecting kidney filtration efficiency—and secondary renal markers over 24 months of GAHT. eGFR was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, which estimates kidney function based on serum creatinine, age, and sex.Methods:We conducted a systematic search of MEDLINE, Cochrane Library, Scopus, and Web of Science up to November 2024. Study quality was assessed using the tool developed by the Effective Public Health Practice Project. Data were synthesized using random-effects models, and heterogeneity was assessed with Cochrane’s Q and I² statistics.Results:Twenty studies were included, representing a total of 2,380 individuals. Pooled analyses showed a significant reduction in eGFR at 6 and 12 months when calculated using the coefficient for sex assigned at birth. When using the affirmed (male) gender, eGFR declined significantly only at 12 months. Overall, eGFR values decreased during the first year and stabilized at 18 and 24 months. This trend likely reflects increased creatinine production due to testosterone-induced muscle mass gain rather than actual renal impairment. Among secondary outcomes, serum creatinine and uric acid levels increased significantly at all time points, while blood urea nitrogen (BUN), a waste product filtered by the kidneys, remained stable at both 6 and 12 months.Conclusions:T-GAHT appears to influence creatinine-based kidney function estimates during the first year of treatment in AFAB individuals. However, these variations are unlikely to be clinically relevant, as supported by stable BUN levels and the absence of reported renal complications. Findings highlight the importance of careful interpretation of eGFR in transgender individuals undergoing masculinizing hormone therapy. Further studies are needed to validate alternative, sex-independent tools for assessing kidney function in this population, particularly in older individuals and those with existing renal disease.