Cardiovascular Risk in Transmasculine Individuals Receiving Testosterone Therapy: Evidence from the Expanded STRONG Cohort Restricted; Files Only

Abstract

Background: Venous thromboembolism (VTE), ischemic stroke (IS), and myocardial infarction (MI) in transmasculine (TM) persons may be related to testosterone use, yet prior research has been limited by insufficient statistical power to draw definitive conclusions.

Objective: To examine the incidence of VTE, IS, and MI in a large, expanded cohort of transmasculine (TM) individuals relative to matched cisgender reference groups, and to assess whether testosterone initiation is associated with elevated acute cardiovascular event (ACVE) risk.

Design: Electronic medical record-based matched cohort study.

Setting: Kaiser Permanente health systems in Georgia, Mid-Atlantic States, Northern California, and Southern California.

Participants: 17,946 TM individuals and 327,212 matched cisgender referents (164,503 women; 162,709 men) in the overall cohort; 9,088 TM individuals with testosterone initiations and 137,587 referents matched with the testosterone initiation subcohort.

Measurements: VTE, IS, and MI ascertained from ICD-9 and ICD-10 diagnostic codes. Follow-up extended to a maximum of 18 years. Adjusted hazard ratios (HR) and the corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by matched set.

Results: TM individuals had significantly elevated rates of VTE relative to both reference women (HR = 1.52; 95% CI 1.18, 1.95) and reference men (HR = 1.42; 95% CI 1.10, 1.84) in the overall cohort; findings were similar in the testosterone initiation subcohort. The rate of IS was elevated but not statistically significant relative to reference women (HR = 1.35; 95% CI 0.99, 1.84) and was not elevated relative to reference men. MI rate was markedly lower compared with reference men (HR = 0.50; 95% CI 0.30, 0.83) and similar to reference women, suggesting MI risk among TM remains within the female-typical range despite testosterone exposure.

Limitations: Cholesterol was missing for a large proportion of younger participants. Hormone use outside the Kaiser Permanente system could not be ascertained.

Conclusions: TM individuals face elevated VTE risk relative to both cisgender reference groups, and suggestive but non-significant elevation in IS risk relative to cisgender women, consistent with partial masculinization of vascular risk. MI risk remains female-typical. These findings underscore the importance of long-term cardiovascular monitoring in TM persons receiving testosterone.

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Abstract

Cover Page

Introduction ............................................................. 1 Methods ................................................................... 4 Study Design and Setting ........................................ 4 Cohort Ascertainment ............................................. 5 Follow-Up ................................................................. 6 Testosterone Exposure .......................................... 6 Outcomes ................................................................ 7 Covariates ............................................................... 7 Statistical Analysis .................................................. 8 Results ..................................................................... 9 Characteristics of Study Participants ................. 9 Venous Thromboembolism ................................... 11 Ischemic Stroke ...................................................... 13 Myocardial Infarction ........................................... 15 Discussion ............................................................. 17 Comparison with Other Research ..................... 20 Conclusions ......................................................... 23

References ................................................................. 24

Tables and Figures ................................................... 29

Table 1. Baseline Characteristics ....................... 29

Figures 1–6. Kaplan-Meier Curves ..................... 30

Table 2. Cox Proportional Hazards Models ...... 32

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health
Keyword	transmasculine testosterone cardiovascular
Committee Chair / Thesis Advisor	Michael Goodman, Emory University

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