Testosterone Therapy Monitoring

Introduction to Testosterone Therapy Risks

• Elevated testosterone levels can stimulate erythropoiesis, increasing hemoglobin and hematocrit levels, which is a significant clinical concern for most individuals, requiring monitoring for specific risks including polycythemia, prostate issues, and cardiovascular effects 1
• The American Urological Association recommends baseline hemoglobin/hematocrit measurement as mandatory for risk assessment, with intervention required if hematocrit exceeds 54% (dose reduction or temporary discontinuation) 2

Hematocrit Monitoring

• Elevated testosterone stimulates erythropoiesis, increasing hemoglobin and hematocrit levels, with injectable testosterone carrying a higher risk of erythrocytosis (up to 44%) compared to transdermal forms (3-18%) 1
• Baseline hemoglobin/hematocrit measurement is mandatory, with intervention needed if hematocrit exceeds 54% 1, 2
• Hemoglobin/hematocrit measurement should be done every 3-6 months initially, then annually 1, 2

Prostate Monitoring

• PSA monitoring is essential for men over 40 years, with evidence not strongly supporting a causative role between testosterone and prostate cancer development 1, 2
• The American Urological Association (AUA) guidelines state that clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer (Strong Recommendation; Evidence Level: Grade B) 2
• Before starting testosterone therapy, baseline PSA measurement and digital rectal examination (DRE) are necessary, and men with abnormal DRE or elevated PSA should have a documented negative prostate biopsy, according to the New England Journal of Medicine 1
• During therapy, PSA monitoring should be done every 3-6 months for the first year, then annually thereafter, along with regular DRE, as recommended by the New England Journal of Medicine 1
• Consider urologic referral for biopsy if PSA increases by more than 1.0 ng/mL during the first six months or more than 0.4 ng/mL per year thereafter, as suggested by the New England Journal of Medicine 1
• The following table summarizes the PSA monitoring guidelines:

Cardiovascular Risk Assessment

• Current evidence suggests neutral or potentially beneficial effects on cardiovascular health, with no consistent evidence linking higher testosterone levels to increased cardiovascular disease risk 1
• Testosterone may improve coronary artery diameter and blood flow, although more research is needed to confirm this 1
• Evaluate both fixed risk factors (age, gender) and modifiable factors (lipids, hypertension, diabetes, smoking) for cardiovascular risk assessment 2

Lipid Profiles and Other Benefits

• Physiologic testosterone levels generally show neutral effects on lipid profiles, with only supraphysiologic doses (well above normal range) significantly reducing HDL levels 1
• Testosterone therapy may help address several issues in cancer survivors, including relief from symptoms of erectile dysfunction, improvement in problems with ejaculation or orgasm for survivors with hypogonadism, and addition of testosterone to PDE5i therapy in individuals with low serum testosterone levels may improve erectile dysfunction 3
• Benefits of testosterone therapy must be weighed against what is known about gender-affirming hormone therapy and hormone-sensitive cancers, and patient preferences should be respected, as some patients may choose to continue testosterone despite potential risks 4

Special Considerations

• For transgender and gender-diverse individuals with cancer, a tailored conversation around whether to continue gender-affirming hormone therapy should be informed by the patient, and their choices should be respected 4
• The AUA notes that testosterone therapy in men with previously treated prostate cancer should be made with caution (Moderate Recommendation; Evidence Level: Grade C) 2
• Men with radical prostatectomy with favorable pathology and undetectable PSA may be candidates for testosterone therapy, according to the AUA guidelines 2