What are the risks of testosterone therapy in men and women?

Risks of Testosterone Therapy in Men and Women

Testosterone replacement therapy carries several significant risks including erythrocytosis, sleep apnea, cardiovascular events, prostate issues in men, and virilization in women, requiring careful monitoring and patient selection.

Risks in Men

Cardiovascular System

• Despite common belief, evidence suggests testosterone therapy may have a neutral or possibly beneficial effect on cardiovascular risk in men, though long-term safety data remains limited 1
• One retrospective study of veterans found increased risk for all-cause mortality, myocardial infarction, and stroke in men treated with testosterone (hazard ratio 1.29) 1
• Testosterone therapy should be used cautiously in men with congestive heart failure due to potential fluid retention 1

Hematologic Effects

• Erythrocytosis is a common side effect with varying risk depending on administration route: 3-18% with transdermal formulations and up to 44% with injections 1
• Regular monitoring of hemoglobin and hematocrit levels is essential during testosterone therapy 2
• Polycythemia may increase blood viscosity and potentially increase thrombotic risk 3

Prostate Effects

• Prostate cancer risk remains controversial with unknown level of risk requiring long-term monitoring 1, 4
• Benign prostatic hyperplasia may worsen with testosterone therapy, though clinical significance is generally low 1
• Patients with benign prostatic hypertrophy may develop acute urethral obstruction requiring cessation of therapy 2

Sexual and Reproductive Effects

• Testicular atrophy and infertility are common, especially in young men, due to down-regulation of gonadotropins 1
• Priapism or excessive sexual stimulation may develop, requiring dose reduction 2
• Oligospermia may occur after prolonged administration or excessive dosage 2

Other Effects

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

Risks in Women

• Virilization effects including acne and hirsutism are common but typically mild and reversible 5
• Changes to lipid profile may occur with oral testosterone but appear less significant with transdermal formulations 5
• Short-term studies (up to 2 years) suggest no increased risk of hepatotoxicity, endometrial hyperplasia, or behavioral hostility at appropriate dosing 5
• No significant adverse cardiovascular effects have been demonstrated in women, including no changes in blood pressure, blood viscosity, or arterial vascular reactivity 5
• Data on breast cancer risk is mixed, with some experimental studies suggesting testosterone might decrease estrogen-induced breast epithelial proliferation 5

Monitoring Recommendations

Baseline Assessment

• Measure PSA and hematocrit/hemoglobin levels 1
• Perform digital rectal examination in men 1
• Assess for history of sleep apnea 1
• Evaluate voiding symptoms through history or standardized measures 1

Follow-up Monitoring

• First follow-up visit at 1-2 months to assess treatment efficacy 1
• Subsequent monitoring every 3-6 months for the first year, then yearly 1
• Regular assessment of symptomatic response, voiding symptoms, and sleep apnea 1
• Monitor for polycythemia, peripheral edema, cardiac and hepatic dysfunction 3
• Consider prostate biopsy for PSA increases of ≥1.0 ng/mL in one year 1

Common Pitfalls and Caveats

• Testosterone should not be used in men with untreated prostate or breast cancer 3
• Oral testosterone preparations should be avoided due to hepatotoxicity risk 1
• Testosterone cypionate should not be interchanged with testosterone propionate due to differences in duration of action 2
• Testosterone therapy may increase sensitivity to oral anticoagulants, requiring dose adjustments 2
• In diabetic patients, testosterone may decrease blood glucose levels and insulin requirements 2
• Despite theoretical concerns, no large-scale, long-term studies have definitively established the relationship between testosterone therapy and prostate cancer 1, 6