Gender-affirming hormone treatment (GAHT) is associated with increased cardiovascular disease risk, particularly during feminising GAHT, with distinct metabolic changes between masculinising and feminising treatments, though no increased risk for type 2 diabetes was observed in transgender cohorts.
Key Findings
Results
No increased risk for type 2 diabetes was found in transgender cohorts undergoing gender-affirming hormone treatment.
Finding based on narrative review of available data from transgender cohorts
Both masculinising and feminising GAHT were considered in this assessment
Despite metabolic changes observed with both forms of GAHT, type 2 diabetes risk was not elevated
Results
Masculinising GAHT increases lean body mass while feminising GAHT is associated with higher fat mass and insulin resistance.
These represent differential effects of sex hormones on body composition in transgender individuals
Feminising GAHT-associated fat mass increase was linked to insulin resistance
These findings parallel known differential effects of sex hormones on metabolism in cisgender people
Results
The risk of cardiovascular disease (CVD) is increased in transgender cohorts, especially during feminising GAHT.
CVD risk elevation was identified as a key concern across transgender populations
Feminising GAHT showed a particularly elevated CVD risk compared to masculinising GAHT
Feminising GAHT is associated with pro-coagulant changes and lower HDL-cholesterol
The review draws parallels to sex hormone replacement in hypogonadism, which is associated with higher vascular risk, especially in ageing individuals
Results
Masculinising GAHT is associated with a more adverse lipid profile, higher haematocrit, and increased blood pressure.
These cardiovascular risk markers were identified through narrative review of available cohort data
The adverse lipid profile, elevated haematocrit, and increased BP represent distinct cardiovascular risk factors from feminising GAHT
These changes contrast with the pro-coagulant and HDL-lowering effects seen in feminising GAHT
Results
Assigned male sex at birth, higher age at initiation of GAHT, and use of cyproterone acetate are separate risk factors for adverse CVD markers.
Three independent risk factors for adverse cardiovascular outcomes were identified
Cyproterone acetate, used as an anti-androgen in feminising GAHT, was specifically identified as a risk factor
Higher age at GAHT initiation mirrors findings in cisgender populations where sex hormone replacement in ageing individuals carries higher vascular risk
Assigned male sex at birth was identified as an independent contributor to CVD risk
Discussion
Metabolic and CVD outcomes may improve during gender-affirming care due to reduction in minority stress, improved lifestyle, and closer surveillance leading to optimised preventive medication.
Transgender identity is noted to be often associated with gender dysphoria and minority stress
Potential beneficial mechanisms include reduction in minority stress, improved lifestyle, and closer medical surveillance
Optimised preventive medication, including statins, was cited as an example of how outcomes may improve
This finding suggests that overall gender-affirming care context may partially offset hormonal cardiovascular risks
Conclusions
GAHT should be individualised according to individual risk factors including drug choice, dose, and form of administration, with discussion of lifestyle and preventive medications.
Recommendations based on narrative review methodology
Individualisation should account for drug type, dose, and route of administration
Physicians are advised to discuss lifestyle modifications and preventive medications to modify metabolic and CVD risk
Follow-up programmes should address usual cardiovascular risk markers while considering that biological age and sex may influence individual risk profiling
Mental health, lifestyle, and novel cardiovascular risk markers during GAHT should be incorporated into follow-up