Do testosterone injections in transgender males increase the risk of cardiac disease?

From the Guidelines

Testosterone injections in transgender males do not significantly increase the risk of cardiac disease, according to the most recent and highest quality evidence. The evidence from studies such as 1 and 1 suggests that the risk of adverse cardiovascular events is low and does not differ significantly between testosterone-treated and placebo groups.

Key Findings

• Low-certainty evidence from 14 trials showed a small increase to no difference in adverse cardiovascular events (Peto odds ratio, 1.22 [CI, 0.66 to 2.23]) 1.
• Moderate-certainty evidence from 8 trials found no evidence of increased risk for serious adverse events or withdrawals due to adverse events with testosterone treatment 1.
• Testosterone treatment improved vitality and fatigue by a less-than-small amount, and showed a less-than-small improvement in depressive symptoms, although most men in the studies did not have baseline depression 1.

Clinical Implications

• Regular cardiovascular monitoring is essential, including blood pressure checks every 3 months during the first year and then annually, along with lipid profiles and hematocrit levels.
• Transgender men with pre-existing cardiovascular disease, uncontrolled hypertension, or a history of thromboembolism should receive careful evaluation before starting testosterone and may require lower doses or alternative administration methods.
• Maintaining healthy lifestyle habits such as regular exercise, balanced diet, avoiding smoking, and limiting alcohol consumption can help mitigate these risks.

Administration and Monitoring

• Transgender men typically receive testosterone in forms such as intramuscular injections (testosterone cypionate or enanthate at 50-100mg weekly or 100-200mg biweekly), transdermal gels (50-100mg daily), or patches (2-6mg daily) 1.
• These treatments can lead to changes in cardiovascular risk factors including increased red blood cell count (erythrocytosis), decreased HDL cholesterol, increased LDL cholesterol, and elevated triglycerides.

From the FDA Drug Label

1. 6 Cardiovascular Risk Long-term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy (5.6).

The use of testosterone injections in transgender males may increase the risk of cardiac disease, as some studies have reported an increased risk of major adverse cardiovascular events (MACE) in association with testosterone replacement therapy in men. However, it is essential to note that the evidence is inconclusive, and long-term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use testosterone injections 2 2.

• Key points:
  • Inconclusive evidence regarding the risk of cardiac disease
  • Some studies report an increased risk of MACE
  • Patients should be informed of the possible risk
  • Long-term clinical safety trials are needed to assess cardiovascular outcomes

From the Research

Testosterone Injections and Cardiac Disease in Transgender Males

• The relationship between testosterone injections and the risk of cardiac disease in transgender males is complex and not fully understood.
• A study published in 2019 3 found that gender-affirming hormone therapy in transgender men can impair lipid profiles, increase homocysteine and leucocytes count, and lead to changes in body composition, which could increase cardiovascular risk.
• Another study from 2019 4 discussed the association between serum levels of endogenous testosterone and cardiovascular disease, but noted that the cardiovascular safety of testosterone replacement therapy remains unclear due to a lack of trials designed to assess cardiovascular events.
• Research from 2014 5 suggested that testosterone deficiency is associated with an increased risk of cardiovascular disease, but also noted that high-dose testosterone can be associated with an increased risk of cardiovascular-related events.
• A review of cardiovascular health in transgender people published in 2018 6 found that trans men on hormone therapy may have an increased risk of cardiovascular disease, including myocardial infarction and stroke, although the evidence is not conclusive.
• A more recent narrative review from 2023 7 found that the administration of cross-sex hormones to transgender people may increase the risk of cardiovascular events, but the evidence is insufficient to guarantee the long-term safety of cross-sex hormone treatment on the cardiovascular system, particularly for transgender men receiving androgen administration.

Key Findings

• Testosterone therapy can lead to changes in metabolic and inflammatory parameters, which could increase cardiovascular risk 3.
• The relationship between testosterone levels and cardiovascular disease is complex, and high-dose testosterone can be associated with an increased risk of cardiovascular-related events 5.
• Transgender men on hormone therapy may have an increased risk of cardiovascular disease, including myocardial infarction and stroke 6.
• The long-term safety of cross-sex hormone treatment on the cardiovascular system is not well established, and further research is needed to fully understand the risks and benefits 7.

Implications for Transgender Males

• Transgender males receiving testosterone injections should be aware of the potential risks and benefits of hormone therapy on their cardiovascular health.
• Regular medical monitoring and appropriate intervention for risk factors of cardiovascular events are necessary to maintain and improve the health of transgender people 7.
• Further research is needed to fully understand the relationship between testosterone injections and cardiac disease in transgender males, and to establish evidence-based guidelines for the safe and effective use of hormone therapy in this population.