Can testosterone supplements cause cerebral hemorrhage?

From the Guidelines

There is no conclusive evidence that testosterone supplements directly cause cerebral hemorrhage in most users, but they may increase risk in certain individuals. Testosterone replacement therapy (TRT) can raise blood pressure and increase red blood cell production (erythrocytosis), potentially leading to thickened blood and increased stroke risk. This is particularly concerning for people with pre-existing hypertension, blood disorders, or cardiovascular disease. Common testosterone preparations include injectable testosterone cypionate (50-400mg every 2-4 weeks), testosterone gel (50-100mg applied daily), or testosterone patches (2-6mg daily). If using testosterone supplements, regular monitoring of blood pressure, hematocrit levels, and cardiovascular health is essential. Warning signs that require immediate medical attention include severe headache, confusion, weakness on one side of the body, vision changes, or difficulty speaking. The risk appears higher with supraphysiologic doses used for bodybuilding compared to prescribed replacement therapy. Anyone considering testosterone therapy should undergo thorough medical screening and maintain regular follow-up appointments with their healthcare provider, as suggested by the American College of Physicians in their 2020 evidence report 1.

Some key points to consider:

• The evidence for the risk of cerebral hemorrhage with testosterone supplements is limited and inconclusive 1.
• Testosterone replacement therapy may have benefits for sexual functioning and quality of life, but the evidence is of low or moderate certainty 1.
• The risk of adverse cardiovascular events, prostate cancer, thromboembolic disease, or death is not well established due to the limited power of the trials 1.
• Regular monitoring and thorough medical screening are essential for individuals considering testosterone therapy, especially those with pre-existing medical conditions 1.

Overall, while the evidence is not conclusive, it is essential to approach testosterone therapy with caution and carefully weigh the potential benefits and risks, prioritizing regular monitoring and thorough medical screening to minimize the risk of adverse events.

From the FDA Drug Label

There is a single report of acute overdosage after parenteral administration of an approved testosterone product in the literature. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident.

Testosterone supplements can cause cerebral hemorrhage in cases of acute overdosage, as evidenced by a reported case of cerebrovascular accident due to extremely high serum testosterone concentrations 2.

From the Research

Testosterone Supplements and Cerebral Hemorrhage

• The relationship between testosterone supplements and cerebral hemorrhage is complex and has been investigated in several studies 3, 4, 5, 6, 7.
• A study published in 2020 found that testosterone aggravates cerebral vascular injury by reducing plasma HDL levels, which can increase the risk of cerebral hemorrhage 3.
• Another study published in 2019 found that testosterone replacement therapy may increase the risk of cardiovascular events, including ischemic stroke and transient ischemic attack, in aging men with low testosterone levels 4.
• However, a more recent study published in 2023 found that testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events in men with hypogonadism and preexisting or a high risk of cardiovascular disease 5.
• Other studies have also investigated the association between serum testosterone levels and cardiovascular disease, including the risk of cerebral hemorrhage 6, 7.
• For example, a study published in 2021 found that lower total testosterone levels were associated with a higher prevalence of hypertension, and that both low and high levels of testosterone were associated with greater cardiovascular risk 7.

Key Findings

• Testosterone supplements may increase the risk of cerebral hemorrhage by reducing plasma HDL levels and increasing inflammation and oxidative stress 3.
• Testosterone replacement therapy may increase the risk of cardiovascular events, including ischemic stroke and transient ischemic attack, in aging men with low testosterone levels 4.
• However, the cardiovascular safety of testosterone-replacement therapy remains unclear, and more research is needed to fully understand its effects 5, 6.
• Serum testosterone levels are inversely associated with the prevalence of hypertension, but both low and high levels of testosterone are associated with greater cardiovascular risk 7.

Mechanisms

• Testosterone may increase the risk of cerebral hemorrhage by reducing plasma HDL levels, increasing inflammation and oxidative stress, and altering blood lipid profiles 3, 4.
• The effects of testosterone on the cardiovascular system are complex and may involve multiple mechanisms, including changes in blood pressure, vascular function, and cardiac structure 5, 6, 7.