Risks of Testosterone Therapy

Cardiovascular Risks

The American College of Cardiology suggests that testosterone therapy may have a neutral or possibly beneficial effect on cardiovascular risk in men, though long-term safety data remains limited 1, 2
Testosterone therapy is associated with an increased risk for all-cause mortality, myocardial infarction, and stroke in men, with a hazard ratio of 1.29 3
The American Heart Association recommends that testosterone therapy should be used cautiously in men with congestive heart failure due to potential fluid retention 4

Erythrocytosis is a common side effect of testosterone therapy, with varying risk depending on administration route: 3-18% with transdermal formulations and up to 44% with injections 1, 5

The American Urological Association states that prostate cancer risk remains controversial with unknown level of risk requiring long-term monitoring 1
Benign prostatic hyperplasia may worsen with testosterone therapy, though clinical significance is generally low 1

The Endocrine Society notes that testicular atrophy and infertility are common, especially in young men, due to down-regulation of gonadotropins 4

The American Academy of Sleep Medicine suggests that sleep apnea may be exacerbated or develop during testosterone therapy, particularly in men with identifiable risk factors 6, 7
Hepatotoxicity is primarily limited to oral testosterone preparations, which are infrequently used in the United States 6
Skin reactions vary by formulation: up to 66% with patches, 5% with gels, and rare with injections 4
Gynecomastia is rare and usually reversible 1

The American College of Physicians recommends measuring PSA and hematocrit/hemoglobin levels at baseline 6
A digital rectal examination should be performed in men at baseline 6
Assess for history of sleep apnea at baseline 6
Evaluate voiding symptoms through history or standardized measures at baseline 6
Consider prostate biopsy for PSA increases of ≥1.0 ng/mL in one year 6

Oral testosterone preparations should be avoided due to hepatotoxicity risk, as recommended by the National Institute of Diabetes and Digestive and Kidney Diseases 6
Despite theoretical concerns, no large-scale, long-term studies have definitively established the relationship between testosterone therapy and prostate cancer, according to the National Cancer Institute 1

The FDA has contraindicated the oral formulation of testosterone undecanoate for age-related hypogonadism, citing demonstrated increases in blood pressure, as recommended by the American College of Physicians, based on evidence from the Annals of Internal Medicine 8