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 therapies to change their bodies to match their gender identity. For transgender women, therapy may include taking hormones such as estrogen.
This research project earlier showed that transgender women who took estrogen had a higher risk of blood clots and strokes than men and women who weren’t transgender. In this study, the research team looked further to learn how different types of hormone therapy affect those risks. The team looked at whether taking estrogen as a pill, a shot, or a patch affected the risk. They also looked at the risks of taking estrogen along with different medicines that decrease testosterone.
What were the results?
Overall, transgender women who took estrogen had a higher risk of blood clots and strokes than men and women who weren’t transgender.
Compared with men and women who weren’t transgender, the risk of blood clots was
- Higher in transgender women who took estrogen as pills
- About the same in transgender women who took estrogen as shots or patches
- Lower in transgender women who took spironolactone rather than other medicines used to lower testosterone
Also, the risk of strokes was
- Higher in transgender women who took estrogen as pills, shots, or patches
- About the same no matter which medicine transgender women took to lower testosterone
Who was in the study?
The research team looked at the health records of 3,325 transgender women and 62,033 men and women who weren’t transgender. All were members of Kaiser Permanente health systems in California. Of these, 55 percent were White, 12 percent were Asian, and 6 percent were Black. Also, 20 percent were Hispanic, and 64 percent were ages 18–36.
What did the research team do?
Using health records, the research team compared the risk of blood clots and strokes in transgender women taking hormone therapy versus men and women who weren’t transgender.
Transgender people, advocates, doctors, and health system staff worked with the research team during the earlier study.
What were the limits of the study?
This study looked at health records from patients in one health system in one state. Hormone therapy may vary across people and health providers. As a result, findings may differ for other patients.
Future research could continue to look at the risks of blood clots and strokes among transgender women. Studies could look at standardized hormone therapy.
How can people use the results?
Transgender women and their doctors can consider the results when starting hormone therapy. They can also look for signs of blood clots and strokes when taking hormone therapy.
Professional Abstract
Objective
To estimate the risk of venous thromboembolism (VTE) and ischemic stroke (IS) in transfeminine people receiving gender-affirming hormone therapy compared with matched cisgender men and women
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | EHRs for 3,325 transfeminine enrollees receiving hormone therapy and 62,033 cisgender male and female enrollees in 2 Kaiser Permanente integrated healthcare systems in Northern and Southern California |
| Interventions/ Comparators |
Not applicable |
| Outcomes | Incidence of VTE and IS |
| Timeframe | Up to 14-year follow-up for study outcomes |
This study expands on an earlier investigation, which found that transfeminine people receiving hormone therapy were at higher risk of VTE and IS than cisgender men and women. The present observational cohort study examined the risk of VTE and IS for various specific hormone therapy regimens, including
- Oral estrogen
- Parenteral estrogen via injection or patches
- Spironolactone plus estrogen
- Other testosterone-suppressing medications plus estrogen
Researchers used electronic health records (EHRs) to identify a cohort of 3,325 transfeminine people, including transgender women and non-binary people, who initiated hormone therapy at two Kaiser Permanente healthcare systems in Southern and Northern California. Researchers matched the transfeminine cohort to 62,033 cisgender members by birth year, race, ethnicity, and enrollment in the same health system during the same time. Researchers compared rates of VTE and IS, controlling for history of cardiovascular events as well as smoking, body mass index, blood pressure, and cholesterol level. Data on hormone use among cisgender members were not available.
Among those included in the analysis, 55% were White, 12% were Asian, and 6% were Black. Also, 20% were Hispanic; 64% were ages 18–36.
Clinicians, healthcare executives, transgender people, and advocates provided input on the previous study, which informed the present study.
Results
Rates of both VTE and IS were higher among transfeminine people who had initiated hormone therapy compared with cisgender males or females.
VTE
- Transfeminine people who started and continued oral estrogen had higher rates of VTE than cisgender males (hazard ratio [HR]: 1.9; 95% confidence interval [CI]: 1.0, 3.5) and females (HR: 2.5; 95% CI: 1.4, 4.5).
- Transfeminine people who started and continued parenteral estrogen had similar rates of VTE as cisgender males (HR: 1.0; 95% CI: 0.4, 2.4) and females (HR: 1.1; 95% CI: 0.4, 2.6).
- Transfeminine people taking testosterone-suppressing medications and estrogen had a less elevated risk of VTE when they took spironolactone rather than other testosterone-suppressing medications such as finasteride or leuprorelin.
IS
- Transfeminine people who started and continued oral estrogen had higher rates of IS than cisgender males (HR: 2.4; 95% CI: 1.2, 4.8) and females (HR: 3.2; 95% CI: 1.5, 7.0).
- Transfeminine people who started and continued parenteral estrogen had higher rates of IS than cisgender males (HR: 2.8; 95% CI: 1.4, 5.6) and females (HR: 4.1; 95% CI: 1.9, 8.7).
- The choice of testosterone-suppressing medication did not affect the risk of IS.
Limitations
Because this study was observational, results do not establish causality. Hormone therapy is not currently standardized. Forming homogenous therapy groups reduced statistical power and limited ability to draw conclusions about therapy formulation and dose.
Conclusions and Relevance
This study confirmed findings that transfeminine people receiving hormone therapy were at higher risk of VTE and IS than cisgender men and women.
Future Research Needs
Future research could examine the risk of thrombotic events among transfeminine people receiving hormone therapy using standardized protocols.
COVID-19-Related Study
COVID-19 Testing, Infections, and Hospital Admissions among People Who Identify as Transgender
Results Summary
In response to the COVID-19 public health crisis in 2020, PCORI launched an initiative to enhance existing research projects so that they could offer findings related to COVID-19. The initiative funded this study and others.
What was this COVID-19 study about?
People who are transgender have a gender identity that differs from the male or female sex assigned to them at birth. The COVID-19 pandemic may affect transgender people differently than others. For example, transgender people often face barriers to receiving timely care, which may delay a COVID-19 diagnosis. Also, transgender people who take gender-affirming hormone therapy may have a higher risk for blood clots if they contract COVID-19.
In this study, the research team wanted to learn about how the COVID-19 pandemic affected transgender people. The team looked at rates of testing, infections, and hospital admissions due to COVID-19. The team compared people who are transgender with people who aren’t transgender.
What were the results?
Compared with people who aren’t transgender, people who are transgender had:
- Higher rates of COVID-19 testing
- Lower rates of having a COVID-19 diagnosis
- No difference in rates for hospital admissions due to COVID-19, including for transgender people who took hormone therapy
Who was in the study?
The research team looked at health records for 11,381 people who are transgender and more than 220,000 people who aren’t transgender. Of the transgender people, 55 percent were White, 10 percent were Asian, 6 percent were Black, 23 percent were Hispanic, and 6 percent were a different or unknown race or ethnicity. About 60 percent were transgender male, and 40 percent were transgender female. Also, 63 percent of transgender people had prescriptions for gender-affirming hormones. All were members of Kaiser Permanente health systems in California.
What did the research team do?
Using health records, the research team compared COVID-19 testing, infections, and hospital stays for transgender people versus people who aren’t transgender. The team matched each record of a person who is transgender to records of 10 men and 10 women who aren’t transgender. Matching was based on traits such as age and race.
What were the limits of the study?
This study looked at records from patients in two health systems in one state. Results may differ for patients in other health systems and states or for people without health insurance.
How can people use the results?
Doctors can use the results to help communicate the risks of COVID-19 to transgender patients.
Professional Abstract
In response to the COVID-19 public health crisis in 2020, PCORI launched an initiative to enhance existing research projects so that they could offer findings related to COVID-19. The initiative funded this study and others.
Background
People who are transgender may be disproportionately affected by the COVID-19 pandemic. For example, transgender people often face barriers to receiving timely care, which may delay a COVID-19 diagnosis. Also, transgender people who take gender-affirming hormone therapy may have a higher risk of blood clots if they contract COVID-19, which may increase risks for hospitalization.
Objective
To characterize the impact of the COVID-19 pandemic on transgender people, as reflected in rates of COVID-19 testing and diagnosis and likelihood of hospitalization due to COVID-19, especially when using gender-affirming hormone therapy
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | EHRs for 11,381 transfeminine and transmasculine members and more than 220,000 cisgender members enrolled in Kaiser Permanente integrated healthcare systems in Northern and Southern California |
| Outcomes | Rate of COVID-19 testing, incidence rate of COVID-19, likelihood of hospitalization due to COVID-19 |
| Data Collection Timeframe | January 1, 2020–July 31, 2021 |
This retrospective observational cohort study compared rates of COVID-19 testing, diagnosis, and hospitalization among transgender and cisgender people.
Researchers used electronic health records (EHRs) to identify 11,381 transgender members enrolled in Kaiser Permanente plans in California. Researchers matched each transgender cohort member to 10 cisgender males and 10 cisgender females by birth year, race and ethnicity, study site, and calendar year of enrollment in the health plan.
Among transgender people in the study, 55% were White, 10% were Asian, 6% were Black, 23% were Hispanic, and 6% were a different or unknown race or ethnicity. Also, 60% were transmasculine, and 40% were transfeminine; 63% received gender-affirming hormone therapy.
Results
COVID-19 testing. Transgender people had a higher rate of COVID-19 testing compared with cisgender people.
- Transfeminine people had an 18% higher rate than cisgender women (hazard ratio [HR]=1.18; 95% confidence interval [CI]: 1.13, 1.24) and a 51% higher rate than cisgender men (HR=1.51; 95% CI: 1.44, 1.59).
- Transmasculine people had a 34% higher rate than cisgender women (HR=1.34; 95% CI: 1.29, 1.40) and a 74% higher rate than cisgender men (HR=1.74; 95% CI: 1.68, 1.81).
COVID-19 incidence rate. Transgender people had a lower risk of a COVID-19 diagnosis than cisgender people.
- Transfeminine people had a 36% lower rate than cisgender women (HR=0.64; 95% CI: 0.56, 0.73) and a 29% lower rate than cisgender men (HR=0.71; 95% CI: 0.62, 0.81).
- Transmasculine people had a 41% lower rate than cisgender women (HR=0.59; 95% CI: 0.53, 0.66) and a 33% lower rate than cisgender men (HR=0.67; 95% CI: 0.60, 0.75).
Hospitalization due to COVID-19. After controlling for sociodemographic factors, vaccination, and comorbidities, the risk of hospitalization due to COVID-19 was not significantly different between transgender people and cisgender people, regardless of whether transgender people received gender-affirming hormone therapy.
Limitations
This study was a retrospective observational analysis of an EHR cohort in two integrated healthcare systems within one state. Results may differ in other healthcare systems and states or for people without health insurance.
Conclusions and Relevance
In this study, transgender people had higher rates of COVID-19 testing and lower rates of COVID-19 diagnosis than cisgender men and women. Hospitalization rates did not differ. Use of gender-affirming hormone therapy did not increase risks associated with COVID-19 for transgender people.
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 assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot 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 descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- Reviewers asked the researchers why they included two different cisgender participant comparison groups, one of males and one of females, rather than one cisgender group comprised of both males and females. The researchers explained that they used two different cisgender groups because male and female healthcare utilization is very different. In addition, they wanted to have hormone serum concentration measurements for comparison from cisgender men and cisgender women because hormone levels in transgender persons may range considerably.
- The reviewers requested more information on what counted as evidence of feminizing or masculinizing gender affirming hormone therapy (GAHT) for the purposes of this study. The researchers added information to the report to explain that they used prescription fill data to determine whether an individual diagnosed with COVID-19 was taking GAHT at the time of diagnosis.
- The reviewers asked whether incidence of thrombotic events was measured and analyzed as a mediator for participants receiving GAHT. The researchers stated that they did not track thrombotic events in this study because their previous studies had shown that the rate of such events was quite low, so they would have been very underpowered to determine whether venous thromboembolism or ischemic stroke mediated rates of COVID-19 infection for their transgender participants. The researchers acknowledged that with a larger number of cases they could conduct these analyses in the future.
- The reviewers asked how the researchers differentiated individuals identifying as gender fluid, gender neutral and nonbinary from individuals identifying as transgender men or women, given that the study used binary categories for transgender status. The researchers admitted that they were unable to distinguish transgender women and transgender men from gender-fluid or non-binary individuals because sexual orientation and gender identity information is often missing in electronic medical records. They used the terms transgender and gender diverse to avoid the differentiation.
- The reviewers asked how hospital admissions due to COVID-19 were separated from all other causes for hospitalizations. The researchers stated that there was reason given in the medical records for hospitalization, but they decided that hospitalization within 30 days of a COVID-19 diagnosis would be assumed related to the virus rather than other causes.
Final Enhancement Report
View this COVID-19 study's final enhancement report.
DOI - Digital Object Identifier: 10.25302/03.3023.ADSS.4532-C19
Final Research Report
View this project's final research report.
More to Explore...
Related PCORI-Funded Research Project
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 assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot 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 descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- A reviewer expressed concern that this project did not seem to formally engage with stakeholders, including transgender women. The researchers explained that this project is a relatively modest extension of the Examining Health Outcomes for People Who Are Transgender research study, which was driven by stakeholder input. The researchers felt that the data analysis undertaken for this report did not require a separate stakeholder engagement component. Instead, they discussed the analysis plans for this project with the advisory group for the original research study, which includes four transgender women.
- A reviewer noted that there are very few studies that examine the effects of hormone therapy on health in the transgender or gender non-conforming communities and said the data in this report could be presented in ways that would be clearer to such patients. The researchers agreed about the dearth of such studies and noted that an advantage of the original research study is that it allows for additional studies to address multiple research questions. While this report was written for a scientific audience, the researchers said they will begin to disseminate their findings to the broader stakeholder community using a different type of communication.