Testosterone-based and estrogen-based gender-affirming hormone therapy cause opposite changes in blood proteins related to heart disease risk, according to a 2026 prospective clinical study of 90 transgender individuals. Testosterone therapy decreased inflammatory markers and certain transport proteins over one year, while estrogen therapy increased them. These findings suggest transgender people may need different cardiovascular monitoring strategies depending on which hormone therapy they receive.
Researchers tracked how gender-affirming hormone therapy affects proteins in the blood that relate to heart disease risk. According to Gram Research analysis, testosterone-based therapy and estrogen-based therapy caused opposite changes in these protective and inflammatory proteins over one year. The study of 55 people starting hormone therapy, plus 35 already on treatment, found that testosterone therapy decreased certain inflammatory markers while estrogen therapy increased them. These findings suggest that transgender individuals may need different heart health monitoring depending on which hormone therapy they receive.
Key Statistics
A 2026 prospective clinical study of 55 transgender individuals starting gender-affirming hormone therapy found that testosterone-based treatment decreased complement proteins and transport proteins over one year, while estrogen-based treatment increased these same proteins.
Research from 2026 involving 90 transgender individuals showed that people receiving estrogen-based hormone therapy had higher levels of C-reactive protein and inflammatory markers compared to those receiving testosterone-based therapy.
A 2026 clinical study tracking 55 people over one year of gender-affirming hormone therapy found that testosterone and estrogen therapy caused opposite directional changes in 19 cardiometabolic proteins related to heart disease risk.
The Quick Take
- What they studied: How different types of gender-affirming hormone therapy change proteins in the blood that affect heart disease risk
- Who participated: 90 transgender individuals: 55 people starting hormone therapy (34 on testosterone, 21 on estrogen) with an average age of 27, plus 35 people already receiving hormone therapy for comparison
- Key finding: Testosterone-based therapy and estrogen-based therapy caused opposite changes in heart-related blood proteins. Testosterone therapy decreased inflammatory markers, while estrogen therapy increased them over one year.
- What it means for you: Transgender people receiving hormone therapy may need personalized heart health monitoring based on which hormone they’re taking. This research suggests one-size-fits-all cardiovascular screening may not be appropriate for all trans individuals.
The Research Details
This was a prospective clinical study, meaning researchers followed the same people over time to watch how their bodies changed. Fifty-five people who had never received gender-affirming hormone therapy were tested at the start and again after one year of treatment. Researchers also included 35 people who were already receiving hormone therapy to compare their results at a single point in time. All participants had their blood tested for 19 different proteins related to heart disease, inflammation, and how the body transports substances through the bloodstream. Researchers also measured body composition using a special type of X-ray scan.
The study separated participants into two groups based on the type of hormone therapy they received. One group received testosterone-based therapy (34 people starting new, 26 already on treatment), and the other received estrogen-based therapy (21 people starting new, 9 already on treatment). By comparing these groups, researchers could see whether different hormones affected the body in different ways.
This approach was important because it allowed researchers to track real changes happening in real people over time, rather than just looking at one moment in time. The one-year timeframe gave enough time to see meaningful changes in blood proteins without waiting for decades to see if heart disease actually developed.
Understanding how hormone therapy affects heart disease risk factors is crucial because transgender individuals have been shown to have higher rates of cardiovascular disease. However, the reasons for this increased risk are not fully understood. By measuring specific proteins involved in inflammation and blood clotting, researchers can identify which aspects of heart health might need extra attention for people on testosterone versus estrogen therapy. This information helps doctors provide better, more personalized care.
This study has several strengths: it followed people over time rather than just taking a snapshot, it used precise laboratory methods to measure blood proteins, and it included both people starting therapy and those already on therapy for comparison. However, the study size was relatively small (90 people total), which means results may not apply to everyone. The study also didn’t follow people for very long (only one year), so we don’t know if these protein changes lead to actual heart problems later. Additionally, the study didn’t include a control group of people not receiving hormone therapy, which would have helped clarify whether the changes were due to the hormones or other factors.
What the Results Show
In people receiving testosterone-based therapy, several important changes occurred over one year. Proteins involved in the complement system (a part of the immune system that helps fight infection and inflammation) decreased, including complement factor H, B, 3, and 4b. Transport proteins, which carry important substances through the bloodstream, also decreased. These include sex hormone-binding globulin, ceruloplasmin, corticosteroid-binding globulin, vitamin D-binding protein, vitronectin, and afamin. One transport protein called transthyretin actually increased. Overall, testosterone therapy appeared to reduce certain inflammatory markers.
In people receiving estrogen-based therapy, the opposite pattern emerged. Complement proteins increased, including complement factor H, B, 3, 4b, and 9. C-reactive protein, a well-known marker of inflammation, also increased. Transport proteins increased as well. This suggests that estrogen therapy may increase inflammatory markers in the blood.
When researchers compared people who had been on estrogen therapy for a while to people just starting estrogen therapy, they found that those already on treatment had higher levels of inflammatory proteins. This pattern was consistent with what they observed in the one-year follow-up group, suggesting these changes happen relatively early in treatment and may persist.
The study also measured body composition changes using X-ray scans, though specific results weren’t detailed in the abstract. These measurements help explain whether changes in blood proteins were related to changes in muscle or fat. The study included people with different starting body weights, with testosterone therapy participants having a median BMI of 26.5 and estrogen therapy participants having a median BMI of 21.5, which may have influenced the results.
Previous research has shown that transgender individuals have elevated cardiovascular disease risk during hormone therapy, but the specific mechanisms were unclear. This study provides new information by measuring specific proteins involved in inflammation and blood clotting. The finding that testosterone and estrogen therapy cause opposite changes in these proteins helps explain why cardiovascular risk might differ between these two groups. However, it’s important to note that measuring these proteins is not the same as proving they cause heart disease, and more research is needed to understand the full picture.
The study had several important limitations. First, the sample size was relatively small (90 people), which means the results may not apply to all transgender individuals. Second, the study only lasted one year, so we don’t know what happens to these proteins over longer periods or whether the protein changes actually lead to heart disease. Third, there was no control group of people not receiving hormone therapy, making it harder to know whether the changes were caused by the hormones or by other factors like age, lifestyle, or genetics. Fourth, the study didn’t measure actual cardiovascular events or outcomes, only blood proteins. Finally, the groups had different numbers of people (more testosterone recipients than estrogen recipients), which could affect the results.
The Bottom Line
Based on this research, transgender individuals receiving gender-affirming hormone therapy should discuss cardiovascular monitoring with their healthcare provider. The type of hormone therapy (testosterone versus estrogen) may require different monitoring approaches. People on testosterone therapy may need monitoring for different risk factors than those on estrogen therapy. However, this research is preliminary and should not change current medical practice without further confirmation. Confidence level: Moderate. The findings are interesting but need to be confirmed in larger studies before making major changes to clinical care.
This research is most relevant for transgender individuals receiving or considering gender-affirming hormone therapy, their healthcare providers, and researchers studying cardiovascular health in transgender populations. It may be less immediately relevant for cisgender individuals (those whose gender identity matches their sex assigned at birth), though understanding how hormones affect the cardiovascular system benefits everyone. People with existing heart disease or heart disease risk factors should definitely discuss these findings with their doctors.
The protein changes measured in this study occurred within one year of starting hormone therapy. However, it’s unclear how long these changes persist or when they might lead to actual heart problems. People should not expect to feel any immediate effects from these protein changes, as they are measured only through blood tests. Long-term monitoring over several years would be needed to understand the full impact on heart health.
Frequently Asked Questions
Does hormone therapy increase heart disease risk in transgender people?
Research shows transgender individuals have elevated cardiovascular disease risk during hormone therapy, but the mechanisms differ by hormone type. This 2026 study found testosterone and estrogen therapy cause opposite changes in inflammatory proteins, suggesting personalized monitoring may be needed rather than assuming all trans people have the same heart risk.
What blood proteins change during testosterone therapy?
A 2026 study found that testosterone-based therapy decreased complement proteins (factor H, B, 3, 4b) and transport proteins including sex hormone-binding globulin, ceruloplasmin, and vitamin D-binding protein over one year. Transthyretin increased. These changes suggest reduced inflammatory markers.
How does estrogen therapy affect inflammation markers?
According to 2026 research, estrogen-based hormone therapy increased inflammatory markers including C-reactive protein and complement proteins (factor H, B, 3, 4b, 9) over one year. Transport proteins also increased, showing an opposite pattern compared to testosterone therapy.
How often should transgender people on hormone therapy get heart checkups?
This study doesn’t specify screening frequency, but the findings suggest personalized monitoring based on hormone type may be beneficial. Transgender individuals should discuss cardiovascular screening schedules with their healthcare providers, as recommendations may differ between testosterone and estrogen therapy recipients.
Can these protein changes predict future heart disease?
This study measured protein changes but didn’t track whether they led to actual heart disease. While these proteins relate to cardiovascular risk, measuring them is not the same as predicting heart attacks or strokes. More long-term research is needed to understand if these changes cause actual heart problems.
Want to Apply This Research?
- Track cardiovascular risk factors monthly: resting heart rate, blood pressure readings, and any symptoms like chest discomfort or unusual shortness of breath. Record the specific type of hormone therapy and dosage to correlate with any changes in these measurements.
- Users should set reminders for regular cardiovascular check-ups based on their hormone therapy type. Create a log of heart-related symptoms or concerns to discuss with healthcare providers. Set goals for heart-healthy behaviors like regular physical activity, stress management, and dietary choices that support cardiovascular health.
- Establish a baseline of cardiovascular measurements before or at the start of hormone therapy. Track these measurements at regular intervals (every 3 to 6 months) and share results with healthcare providers. Note any changes in energy levels, exercise tolerance, or heart-related symptoms. Over time, this data helps identify personal patterns and whether additional medical monitoring is needed.
This research describes changes in blood proteins during gender-affirming hormone therapy but does not prove these changes cause heart disease. The study was relatively small and only lasted one year. Transgender individuals receiving or considering hormone therapy should discuss cardiovascular health monitoring with their healthcare providers. This article is for educational purposes and should not replace professional medical advice. If you experience chest pain, shortness of breath, or other heart-related symptoms, seek immediate medical attention.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.