The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney Function: A Systematic Review and Meta-Analysis

Background and objectives: Gender-affirming hormone therapy modifies body composition and lean muscle mass in transgender persons. We sought to characterize the change in serum creatinine, other kidney function biomarkers, and GFR in transgender persons initiating masculinizing and feminizing gender-affirming hormone therapy.

Design, setting, participants, & measurements: We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to September 16, 2020 for randomized controlled trials, observational studies, and case series that evaluated the change in serum creatinine, other kidney function biomarkers, and GFR before and after the initiation of gender-affirming hormone therapy in adult transgender persons. Two reviewers independently screened and abstracted data, and disagreements were resolved by a third reviewer. A random effects meta-analysis was performed to determine the change in outcomes over follow-up of 3, 6, and 12 months.

Results: Of the 4758 eligible studies, 26 met the inclusion criteria, including nine studies that recruited 488 transgender men and 593 women in which data were meta-analyzed. There was heterogeneity in study design, populations, gender-affirming hormone therapy routes, and dosing. At 12 months after initiating gender-affirming hormone therapy, serum creatinine increased by 0.15 mg/dl (95% confidence interval, 0.00 to 0.29) in 370 transgender men and decreased by -0.05 mg/dl (95% confidence interval, -0.16 to 0.05) in 361 transgender women. No study reported the effect of gender-affirming hormone therapy on albuminuria, proteinuria, cystatin C, or measured GFR.

Conclusions: Gender-affirming hormone therapy increases serum creatinine in transgender men and does not affect serum creatinine in transgender women. The effect on gender-affirming hormone therapy on other kidney function biomarkers and measured GFR is unknown.

Clinical trial registry name and registration number: Change in Kidney Function Biomarkers in Transgender Persons on Gender Affirmation Hormone Therapy-A Systematic Review and Meta-Analysis, CRD42020214248.