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

Objective: The impact of testosterone-based gender affirming hormone therapy (T-GAHT) on kidney function in transgender individuals assigned female at birth (AFAB) remains a matter of clinical uncertainty and debate. This study aimed to quantify through a meta-analytical approach the changes in estimated glomerular filtration rate (eGFR), a widely used clinical parameter that reflects how efficiently the kidneys filter waste products from the blood, and in secondary markers of kidney functions in this population during 24 months of GAHT. The eGFR was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, which estimates kidney filtration based on serum creatinine, age, and sex. Methods: A thorough search of MEDLINE, COCHRANE LIBRARY, SCOPUS and WEB OF SCIENCE databases was carried out to identify suitable studies. Quality of the articles was scored using the Effective Public Health Practice Project. Data were combined using random effects models and the between-study heterogeneity was assessed using Cochrane's Q and I Results: Twenty included studies provided information about an overall sample of 2380 individuals. The pooled estimates documented a significant decrease in eGFR (CKD-EPI equation) at 6 and 12 months with respect to baseline, using the attributed (female) gender. When the CKD-EPI equation was referred to the perceived (male) gender, eGFR significantly decreased after 12 months but not after 6 months of T-GAHT. The trend of eGFR values showed a transient decline during the first year of therapy, followed by stabilization at 18 and 24 months. This pattern is likely attributable to increased creatinine production due to testosterone-induced gains in muscle mass, rather than to a true decline in kidney function. Among the secondary outcomes, pooled estimates revealed significant increases of creatinine and uric acid levels at all follow-up times. On the contrary, blood urea nitrogen (BUN), a waste product filtered by the kidneys and commonly used to assess renal function, did not change significantly after either 6 months or 12 months of T-GAHT. Conclusions: The influence of T-GAHT on eGFR in the first two years in healthy, young AFAB transgender individuals appears to be statistically significant, but is likely not clinically relevant. This interpretation is supported by the stability of BUN levels and the absence of adverse renal events in the included studies, suggesting preserved kidney function despite changes in creatinine-based estimates. Further research is warranted to identify more accurate tools for evaluating kidney function in this population, particularly during the early months of treatment or in individuals with pre-existing renal conditions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024596106.