Does a perimenopausal female on testosterone (hormone replacement therapy) for gender affirmation have an increased risk for pulmonary embolism (PE)?

From the Guidelines

Perimenopausal females on testosterone for transgender purposes may have an increased risk for pulmonary embolism (PE), although the evidence is not as robust as for estrogen therapy in transgender women. The risk of venous thromboembolism, including PE, is a concern with hormone replacement therapy (HRT), as seen in studies on estrogen and progestin therapy 1. Testosterone can potentially increase clotting factors, red blood cell count (erythrocytosis), and blood viscosity, all of which may contribute to thrombotic risk. This risk may be further complicated during perimenopause, when hormonal fluctuations are already occurring.

Key Considerations

• The risk appears to be dose-dependent, with higher doses of testosterone potentially carrying greater risk.
• Healthcare providers typically monitor hematocrit and hemoglobin levels regularly, aiming to keep hematocrit below 50% to minimize this risk.
• If levels become elevated, dose adjustments or temporary discontinuation of testosterone may be necessary.
• Other risk factors such as smoking, obesity, personal or family history of clotting disorders, and sedentary lifestyle can compound this risk.

Recommendations

• Transgender individuals on testosterone therapy should be aware of PE symptoms including sudden shortness of breath, chest pain, rapid heart rate, and coughing up blood, and seek immediate medical attention if these occur.
• Regular monitoring and management of risk factors are crucial to prevent PE in perimenopausal females on testosterone therapy.
• The most recent and highest quality study on this topic should be consulted for the most up-to-date recommendations, however, based on available data, testosterone therapy in perimenopausal transgender females should be approached with caution and careful monitoring due to the potential increased risk of PE 1.

From the FDA Drug Label

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), have been reported in patients using testosterone products. The use of testosterone products, including in a perimenopausal female on testosterone for transgender, may have an increased risk for pulmonary embolism (PE) due to the reported cases of venous thromboembolism (VTE) in patients using these products 2.

From the Research

Risk of Pulmonary Embolism in Perimenopausal Females on Testosterone Therapy

• The risk of pulmonary embolism (PE) in perimenopausal females on testosterone therapy for transgender individuals is a concern due to the potential thrombogenic effects of testosterone 3, 4.
• A study published in 2005 found that the addition of testosterone to hormone therapy regimens improved sexual function scores for postmenopausal women, but also resulted in a significant decrease in high-density lipoprotein (HDL) cholesterol levels 5.
• However, there is limited evidence on the specific risk of PE in perimenopausal females on testosterone therapy, and more research is needed to fully understand this risk 6, 7.
• A narrative review published in 2023 noted that transgender individuals using masculinizing hormone therapy, such as testosterone, may be at increased risk of polycythemia and cardiovascular disease, including myocardial infarction and stroke 6.
• Another study published in 2024 found that transgender patients assigned female at birth (AFAB) on testosterone therapy may be at risk of cardiovascular disease and stroke, although the evidence is inconsistent and more research is needed 7.

Thrombogenic Effects of Testosterone

• Testosterone has been shown to have thrombogenic effects, increasing the risk of venous thromboembolism (VTE) and pulmonary embolism (PE) in some individuals 3, 4.
• A case report published in 2023 described a 19-year-old male who developed multiple pulmonary emboli and deep vein thrombosis after using testosterone for one month 4.
• The exact mechanism of the thrombogenic effects of testosterone is not fully understood, but it is thought to involve changes in blood clotting factors and platelet function 3.

Clinical Implications

• Clinicians should be aware of the potential risks of testosterone therapy in perimenopausal females, including the risk of PE and cardiovascular disease 6, 7.
• Regular monitoring of blood clotting factors and cardiovascular risk factors is recommended for individuals on testosterone therapy 6, 7.
• Further research is needed to fully understand the risks and benefits of testosterone therapy in perimenopausal females and to develop evidence-based guidelines for its use in this population 6, 7.