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Stroke and Blood Clot Risk in Transgender Women Taking Hormones

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Results Summary and Professional Abstract

Results Summary
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Results Summary

Ongoing COVID-19 Project Enhancement

This study received additional funding in 2020 to quickly initiate new research related to COVID-19. The additional research is in progress. PCORI will post the research findings on this page once the results are final.

COVID-19 may affect transgender people more than others. For example, barriers to timely care may delay diagnosis. Also, transgender people who take gender affirming hormone therapy may have a higher risk for blood clots, which are a sign of severe COVID-19.

With this enhancement, the research team will use data from health records to

  • Compare rates of COVID-19 testing in transgender men and women by age, race, and ethnicity
  • Determine the number of COVID-19 cases among transgender and cisgender people who were tested
  • Look at the severity of COVID-19 among transgender and cisgender people
  • Assess whether gender-affirming therapy affects how COVID-19 progresses and patient health outcomes

Enhancement Award Amount: $494,296

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

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.

This project's final research report is expected to be available by November 2021.

Related PCORI-funded Research Project

Examining Health Outcomes for People Who Are Transgender

More on this 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.

Conflict of Interest Disclosures

The COI disclosure form  for this project will be posted here soon.

Project Details

Principal Investigator
Michael Goodman, MD, MPH
Project Status
Completed; PCORI Public and Professional Abstracts Posted
Project Title
Acute Thrombotic Events Following Feminizing Hormone Therapy
Project End Date
December 2022
Organization
Emory University
Year Awarded
2018
State
Georgia
Year Completed
2021
Project Type
Research Project
Health Conditions  
Mental/Behavioral Health
Gender Dysphoria
Intervention Strategies
Drug Interventions
Other Clinical Interventions
Populations
LGBTQ
Low Income
Veterans
Funding Announcement
Addressing Disparities
COVID-19-Related Project Enhancement
Project Budget
$817,383
Page Last Updated: 
April 12, 2021