Results Summary
What was the research about?
People who are transgender have a gender identity that differs from the male or female sex assigned to them at birth. Some transgender people get gender-affirming therapies to change their bodies to match their gender identity. Examples of gender-affirming therapies include surgery or taking hormones such as estrogen or testosterone.
The research team wanted to learn about health outcomes for transgender people. To do this, the team compared certain health measures among people who are transgender with the same measures among people who aren’t transgender. The study also looked at health outcomes for transgender people who did and didn’t receive gender-affirming therapies.
What were the results?
- Mental health. Nearly all mental health conditions the research team looked at, such as depression, were more common among transgender people than people who aren’t transgender. Self-harm and thoughts about suicide were more common among transgender youth ages 10 to 17 years than nontransgender youth of the same age.
- Cancers. Compared with men who aren’t transgender, transgender women had a lower risk of prostate cancer and a higher risk of cancers that arise from endocrine glands, such as thyroid cancer.
- Blood clots and strokes. Transgender women who received estrogen had a higher risk of blood clots and strokes compared with men and women who aren’t transgender. Their risk for blood clots and strokes increased over time.
- Body image. Transgender people who received more gender-affirming therapies reported that they felt better about how their bodies looked and how other people saw them compared with transgender people who received fewer or no therapies.
Who was in the study?
The research team looked at health records for 6,459 transgender people and 127,668 nontransgender people. All were members of three Kaiser Permanente health systems in Georgia and California. In addition, 697 transgender members took a survey.
What did the research team do?
Using health records for transgender and nontransgender people from three health systems over 10 years, the team compared the risk of blood clots or strokes. The team also looked at other health outcomes, such as cancer and mental health conditions.
The team sent a survey to transgender people whose health records showed that they had received gender-affirming therapies. The survey asked transgender people about the therapies they received. It also asked how they felt about the way their bodies looked after receiving any therapies.
A group of transgender people, advocates, doctors, and health system staff worked with the research team during the study.
What were the limits of the study?
This study looked at records from patients in three health systems in two states. Results may be different for patients in other health systems or for people without health insurance. The research team can’t say for sure that the risks for blood clots and strokes found among transgender patients in the study are a result of hormone therapy. Other health problems may have led to the blood clots and strokes.
Future research could look at other health benefits and risks of gender-affirming therapies for transgender patients.
How can people use the results?
These results can help transgender people who get gender-affirming therapies and their doctors be more aware of possible health problems, such as blood clots or strokes. Doctors may also want to ask transgender patients about possible mental health needs. Transgender women and their doctors may also want to be on the lookout for thyroid and some other cancers.
Professional Abstract
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
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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.
Final Research Report
View this project's final research report.
Journal Citations
Article Highlight: This study examined the largest cohort of transgender people in research to date. The researchers reported in Annals of Internal Medicine that transgender women who receive estrogen treatments may face a higher risk for stroke and dangerous blood clots than previously thought. In a guest blog post, the project lead and a stakeholder partner discuss the findings and what additional research could help transgender people make informed decisions about their health.
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also confirms that the research has followed PCORI’s Methodology Standards. During peer review, experts who were not members of the research team read a draft report of the research. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. Reviewers do not have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve how the research team analyzed its results or reported its conclusions. Learn more about PCORI’s peer-review process here.
In response to peer review, the PI made changes including
- Specifying in the abstract that although there was increased risk of venous thromboembolism (VTE) and ischemic stroke (IS) after 6 years of estrogen therapy for transgender females compared to cisgender males, the overall rate of these events was relatively low, with a wide distribution in the risk estimates.
- Expanding the description of the difficulties that the researchers experienced in completing the portion of the study within the Veterans’ Administration (VA) system. Reviewers gave varied advice about how to deal with this part of the study, and the researchers felt it was important, especially since this was part of the original protocol, to present the VA findings and their insights into dealing with difficulties of data collection.
- Removing the presentation of analyses and results associated with a within-group analysis among transgender females based on when they started hormone therapy. The researchers found that using the hormone therapy as a basis for inclusion in the analysis, and then also differentiating within the group by when patients received the therapy, led to concerns about the complexity and the validity of those analyses.
- Acknowledging in the Discussion that the transgender population captured in the insured cohort used in this study may not reflect the transgender population of the United States, particularly in relation to income and insurance access. This limited the generalizability of the findings.
Finally, reviewers acknowledged that a key strength of this study was the incorporation of both risks and benefits of gender affirmation care in their study. Per reviewers’ request, the researchers expanded the discussion of the benefits of such care in the report.