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

Testosterone-based gender affirming hormone therapy (T-GAHT) produced a significant decrease in eGFR calculated using the attributed (female) gender at both 6 and 12 months from baseline.

• The eGFR was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation based on serum creatinine, age, and sex.
• 20 included studies provided information about an overall sample of 2380 individuals.
• The pooled estimates documented a significant decrease in eGFR at 6 and 12 months with respect to baseline when using the attributed (female) gender.
• Data were combined using random effects models with between-study heterogeneity assessed using Cochrane's Q and I2.

When eGFR was calculated using the perceived (male) gender in the CKD-EPI equation, the significant decrease was observed at 12 months but not at 6 months of T-GAHT.

• The CKD-EPI equation incorporates sex as a variable, so results differed depending on whether attributed (female) or perceived (male) gender was used.
• At 6 months, the decrease in eGFR using perceived (male) gender was not statistically significant.
• At 12 months, the decrease remained statistically significant even when using perceived (male) gender.

The trend of eGFR values showed a transient decline during the first year of T-GAHT, followed by stabilization at 18 and 24 months.

• eGFR values declined during months 1–12 but stabilized at the 18- and 24-month follow-up time points.
• This pattern is likely attributable to increased creatinine production due to testosterone-induced gains in muscle mass rather than a true decline in kidney function.
• The meta-analysis covered up to 24 months of follow-up.

Creatinine and uric acid levels were significantly increased at all follow-up time points during T-GAHT.

• Pooled estimates revealed significant increases of creatinine and uric acid levels at all follow-up times examined.
• Elevated creatinine was interpreted as reflecting testosterone-induced muscle mass gains rather than renal impairment.
• These were classified as secondary outcomes in the meta-analysis.

Blood urea nitrogen (BUN) did not change significantly after either 6 or 12 months of T-GAHT.

• BUN is a waste product filtered by the kidneys and commonly used to assess renal function.
• No significant change in BUN was found at the 6-month follow-up.
• No significant change in BUN was found at the 12-month follow-up.
• The stability of BUN levels supports the interpretation that kidney function was preserved despite creatinine-based eGFR changes.

No adverse renal events were reported in any of the included studies during up to 24 months of T-GAHT.

• The absence of adverse renal events across all 20 included studies supports the conclusion that kidney function was preserved.
• This finding, combined with stable BUN levels, suggests the eGFR changes are not clinically relevant.
• The study population consisted of healthy, young AFAB transgender individuals.

The meta-analysis included 20 studies with a combined sample of 2380 AFAB transgender individuals receiving T-GAHT.

• A thorough search of MEDLINE, COCHRANE LIBRARY, SCOPUS, and WEB OF SCIENCE databases was carried out.
• Quality of the articles was scored using the Effective Public Health Practice Project tool.
• The study was prospectively registered on PROSPERO (identifier CRD42024596106).
• Data were combined using random effects models.