Incidence of malignant and premalignant conditions in LGBTQIA+ individuals on gender-affirming hormone therapy: A systematic review and meta-analysis.

Abstract

e22580 Background: LGBTQIA+ individuals comprise approximately 7.1% of the U.S. population. Gender-affirming hormone therapy (GAHT) is integral to transition for many but has been linked—though inconclusively—to increased risks of certain malignancies, such as breast and prostate cancer. Large-scale studies for this topic are limited, particularly for non-binary individuals. Moreover, cancer screening rates in this population are low, highlighting the need for robust epidemiological data and improved clinical awareness among healthcare professionals. Methods: We searched PubMed from inception to January 27, 2025, per PRISMA guidelines. Included studies were RCTs and observational studies on malignancies in LGBTQIA+ individuals on GAHT, excluding case reports, series, reviews, and non-English studies. Outcomes were analyzed using a random-effects model in RevMan 5.4 and a P value < 0.05 was considered significant. Results: Among 292 studies, 18 met the inclusion criteria, comprising 112,108 patients. Among these, 96% underwent male-to-female (MTF) transition, 3.5% female-to-male (FTM), and 0.2% identified as non-binary/queer.Feminizing therapy was received by 96% of patients, while 3.7% received masculinizing therapy. The overall incidence of cancer and precancerous lesions was 0.075%. GAHT had no significant impact on cancer risk (relative risk (RR) = 0.55, 95% CI 0.22-1.39, p = 0.21). Subgroup analyses based on feminizing or masculinizing therapy and type of cancer studied (breast or cervical) also showed no significant difference (p = 0.08, 0.62 respectively). Conclusions: Our study, the largest review on GAHT and cancer risk, found no significant association but highlights key gaps in research and clinical practice. While current evidence does not confirm increased cancer risk, study heterogeneity limits definitive conclusions. These findings emphasize the need for standardized long-term cohort studies to better assess cancer risk across different GAHT regimens, durations, and individual risk factors.