Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study
Open accessAbstract
Background: Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use. Objective: To examine the incidence of these events in a cohort of transgender persons. Design: Electronic medical record-based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment. Setting: Kaiser Permanente in Georgia and northern and southern California. Patients: 2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women. Measurements: VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts. Results: Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants. Limitation: Inability to determine which transgender members received hormones elsewhere. Conclusion: The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen. Primary Funding Source: Patient-Centered Outcomes Research Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.
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The adjusted HR for VTE with estrogen use in transgender women was 3.2 (95% CI 1.5-6.5) compared to cisgender men and 2.5 (1.2-5.0) compared to ciswomen.
“The adjusted HR for VTE with estrogen use in transgender women was 3.2 (95% CI: 1.5–6.5) compared to cisgender men, and 2.5 (1.2–5.0) compared to ciswomen, which increased with longer duration of use.”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [121]
The same study found an increased risk of ischemic stroke among transwomen using estrogens, with hazard risks after 6 years of 9.9 (3.0-33.1) compared to cismen and 4.1 (1.5-11.4) compared to ciswomen.
“The researchers of the same study also found an increased risk of ischemic stroke among transwomen using estrogens, where the hazard risks after 6 years of use were 9.9 (3.0– 33.1) compared to cismen and 4.1 (1.5– 11.4) compared to ciswomen.”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [121]
In a U.S. database study of 2,842 transwomen and matched cisgender men and women, transwomen had a higher incidence of VTE than both reference populations, and risk increased over time.
“The researchers found that transwomen had a higher incidence of VTE than both reference populations, and that risk increased over time.”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [121]
The incidence of myocardial infarction was similar in transwomen compared to matched controls.
“The incidence of myocardial infarction was similar in transwomen compared to the matched controls.”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [121]
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- Authors
- Getahun, D., Nash, R., Flanders, W. D., Baird, T. C., Becerra-Culqui, T. A., Cromwell, L., Hunkeler, E., Lash, T. L., Millman, A., Quinn, V. P., Robinson, B., Roblin, D., Silverberg, M. J., Safer, J., Slovis, J., Tangpricha, V., & Goodman, M.
- Affiliations
- Kaiser Permanente (US)
- Emory University (US)
- Icahn School of Medicine at Mount Sinai (US)
- ORCID
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2018-08-21
- Volume
- 169
- Issue
- 4
- Pages
- 205-213
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC6636681
- OpenAlex
- W2865707913
- Cited by
- 431
- References
- 31
- Citations by year
- 2026: 41 · 2025: 59 · 2024: 61 · 2023: 57 · 2022: 65 · 2021: 56 · 2020: 46 · 2019: 33 · 2018: 12
- FWCI
- 49.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Patient-Centered Outcomes Research Institute (AD-12-11-4532)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD076387)
- Topics
- Social Sciences › Psychology › Social Psychology › LGBTQ Health, Identity, and Policy
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- transgender health, cross-sex hormones, estrogen, venous thromboembolism, ischemic stroke, myocardial infarction, transfeminine, transmasculine, cardiovascular risk
- MeSH terms
- Adolescent, Adult, California, Brain Ischemia, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Myocardial Infarction, Gonadal Steroid Hormones, Transsexualism, Incidence, Estradiol Congeners, Venous Thromboembolism, Young Adult, Electronic Health Records
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