Five-Year Fracture Rate for Transgender and Gender Diverse Patients on Gender-Affirming Hormone Therapy

Gender-affirming hormone therapy (GAHT) is a cornerstone of gender-affirming care for transgender and gender diverse (TGD) patients, with a direct biological role on bone metabolism. However, a paucity of data describes how GAHT influences fracture rate over time. The study's primary objective was to describe the 5-year all-cause fracture incidence rate (IR) among TGD patients initiating estrogen-based GAHT (E-GAHT) or testosterone-based GAHT (T-GAHT), compared with TGD patients not using GAHT (non-GAHT).

This retrospective cohort study of TGD adults aged 18 to 65 years used insurance data from the Merative MarketScan Commercial Database (MarketScan) from January 1, 2009, to December 31, 2019. The main outcome was IR (IR with 95% confidence intervals [CIs]) of all-cause fracture after up to 5 years of follow-up. The IR ratio was estimated by comparing E-GAHT and T-GAHT groups with the non-GAHT group. Cox proportional hazards regression models estimated the hazard ratio (HR) of fracture after adjusting for age, comorbidity status using Charlson Comorbidity Index (CCI), recent fractures, and study start year.

Nine thousand six hundred ninety-six TGD adults (E-GAHT [n = 1,131]; T-GAHT [n = 1,046]; non-GAHT [n = 7,519]) were identified using clinical and enrollment criteria. No differences in age (mean age [SD], 33.4 [13.2] years, 30.8 [11.7] years, and 33.2 [13.6] years, respectively) and CCI (percent with CCI = 0 [%CCI = 3+]; 86.7% [2.2%], 84.9% [1.4%], and 85.3% [1.9%]) were observed by group. The fracture IR was 13.9 (95% CI, 9.1 to 18.8) for E-GAHT, 15.3 (95% CI, 10.1 to 20.4) for T-GAHT, and 19.2 (95% CI, 16.9 to 21.4) for non-GAHT. Compared with non-GAHT, the crude IR ratio and fully adjusted HR was 0.73 (95% CI, 0.51 to 1.04) and 0.71 (95% CI, 0.49 to 1.02), respectively, for E-GAHT and 0.80 (95% CI, 0.56 to 1.14) and 0.78 (95% CI, 0.55 to 1.12), respectively, for T-GAHT.

Based on United States commercial claims data, the use of GAHT was not associated with 5-year all-cause fracture IR.

III.