Clinically relevant cardiometabolic changes associated with testosterone-based gender-affirming hormone therapy in transmasculine individuals: a systematic review and meta-analysis

Background Testosterone-based gender-affirming hormone therapy is a key component of care for many transmasculine individuals, but its cardiometabolic effects remain incompletely characterized. Routinely monitored biomarkers may provide clinically relevant information because major cardiovascular events are uncommon and difficult to interpret in available cohorts.Objective To synthesize and clinically interpret changes in BMI, hemodynamic, hematological, and lipid outcomes during testosterone therapy in transmasculine individuals.Methods EMBASE, CINAHL, MEDLINE/PubMed, Cochrane Library, and Scopus were searched from inception through April 7, 2026. Eligible studies were randomized trials or observational investigations of transmasculine individuals receiving testosterone therapy and reporting body mass index, systolic or diastolic blood pressure, hemoglobin, hematocrit, or lipid outcomes. Two reviewers independently screened studies, assessed eligibility, and extracted data. Risk of bias was evaluated with RoB 2 or ROBINS-I, and certainty of evidence with GRADE. Random-effects meta-analyses used mean differences or standardized mean changes. Laboratory units were harmonized when necessary, and pooled estimates were contextualized using clinically informed benchmarks.Results Sixty-two studies were included, of which 39 contributed to at least one meta-analysis. Testosterone therapy was associated with increased hemoglobin, hematocrit, LDL cholesterol, total cholesterol, triglycerides, systolic and diastolic blood pressure, and body mass index, and with reduced HDL cholesterol. Hematocrit and lipid changes were the most consistent findings, whereas hemoglobin and blood pressure estimates were less stable after adjustment for potential publication bias.Conclusion Testosterone therapy in transmasculine individuals is associated with measurable cardiometabolic changes, with the most consistent evidence for increased hematocrit and a directionally unfavorable lipid profile. These findings support ongoing clinical monitoring but do not permit definitive inference about long-term cardiovascular events.