Objective

To examine (1) the incidence of acute cardiovascular events and cancers and the prevalence of mental health conditions among transgender and cisgender people; and (2) perceived benefits of gender-affirming therapies such as hormones or surgery among transgender people

Study Design

Design Elements	Description
Design	Observational: cohort study Observational: cross-sectional study
Population	Cohort study: EHRs for 6,459 transgender members and 127,668 cisgender members enrolled in 3 Kaiser Permanente integrated healthcare systems in Georgia and Northern and Southern California Cross-sectional study: survey responses of 697 transgender enrollees
Interventions/ Comparators	Not applicable
Outcomes	Cohort study: incidence of acute cardiovascular events and cancers, prevalence of mental health conditions Cross-sectional study: perceived body image, transgender congruence, and satisfaction with gender-passing status
Timeframe	Cohort study: up to 10-year follow-up for study outcomes Cross-sectional study: not applicable

Although there are guidelines for the clinical care of transgender patients, many issues in transgender health and gender-affirmation therapy remain unresolved because of a lack of evidence. The researchers conducted a cohort and cross-sectional study to help fill these gaps.

For the cohort study, researchers used International Classification of Diseases, Ninth Revision codes and keyword searches of free-text clinical notes within electronic health records (EHRs) to identify 6,459 transgender people ages 3–86 enrolled in Kaiser Permanente integrated healthcare systems in Georgia and California between January 1, 2006, and November 30, 2016. Researchers categorized each cohort member as transfeminine or transmasculine and noted whether each had received hormones, surgery, or other gender-affirming therapies. Within the transgender cohort, 54% were transfeminine and 63% had gender-affirming therapy noted in their EHRs. Researchers matched the transgender cohort to 127,668 cisgender members on birth year, race/ethnicity, and enrollment in the same health system during the same time. Researchers compared rates of cardiovascular and cancer events and the prevalence of mental health conditions in both cohorts.

For the cross-sectional study, researchers mailed survey invitations to 2,136 adult transgender enrollees with evidence of gender-affirming care in their EHRs. Researchers examined the association between reported receipt of gender-affirming therapies and body image perceptions in 697 completed surveys.

A stakeholder advisory group including clinicians, healthcare executives, and transgender people and advocates provided input on the study design and data analysis.

Results

• Incidence of acute cardiovascular events. After more than six years from estrogen initiation, transfeminine enrollees who used oral estrogen were at higher risk of blood clots than cisgender males (95% confidence interval [CI] 2.0, 29.8) and females (95% CI 2.8, 39.5). Transfeminine enrollees who used oral estrogen had a higher stroke risk than cisgender males (95% CI 1.6, 28.1); this difference was most notable after six to seven years of follow-up.
• Incidence of cancer. Compared with cisgender males, transfeminine enrollees were at lower risk for prostate cancer (95% CI 0.2, 0.9) but higher risk for endocrine gland cancers (95% CI 1.8, 15.1) and viral infection-induced cancers (95% CI 1.0, 3.9). Transfeminine enrollees were also at higher risk for lymphatic and hematopoietic cancers (95% CI 1.4, 6.3) than cisgender females.
• Prevalence of mental health conditions. Nearly all mental health diagnoses examined were more common among transgender children, adolescents, and adult enrollees than cisgender enrollees. The prevalence of suicidal ideation (95% CI 17.8, 150.0) and self-inflicted injuries (95% CI 8.5, 559.1) was significantly higher for transfeminine enrollees ages 10–17 than cisgender males of the same age. The prevalence of suicidal ideation (95% CI 21.9, 80.7) and self-inflicted injuries (95% CI 32.9, 577.2) was significantly higher for transmasculine enrollees ages 10–17 than cisgender males of the same age.
• Perceived body image, transgender congruence, and satisfaction with gender-passing status. Scores on body image, transgender congruence, and satisfaction with gender-passing status scales were significantly higher among transgender enrollees who had completed their gender affirmation than those who reported fewer or no therapies (p<0.01). Satisfaction with gender-passing status was significantly higher for transmasculine than transfeminine enrollees (p<0.05).

Limitations

Because this study was an observational data analysis of an EHR cohort and a cross-sectional survey, the results do not establish causality. Results may be different in other health systems or for uninsured people. For the survey, researchers were able to contact only enrollees whose Kaiser Permanente EHR had evidence of transgender-related care.

Conclusions and Relevance

Clinicians may want to monitor transgender people receiving gender-affirming therapies for blood clots, strokes, certain types of cancer, and mental health needs.

Future Research Needs

Collecting longitudinal data from a larger group of patients in other health systems could add to the evidence about the effects of gender-affirming therapies.