What are the contraindications to testosterone therapy?

Contraindications to Testosterone Therapy

Testosterone therapy is absolutely contraindicated in men with breast cancer, known or suspected prostate cancer, men actively seeking fertility, and pregnant women (or their male partners due to transfer risk). 1, 2, 3

Absolute Contraindications

Malignancy

• Male breast cancer (active or previously treated) is an absolute contraindication due to testosterone's conversion to estradiol and limited safety data in this population 1, 2
• Known or suspected prostate cancer remains a formal FDA contraindication, though this is increasingly controversial based on emerging evidence 3
• Carcinoma of the breast in men is explicitly listed as an FDA contraindication 3

Fertility Concerns

• Men actively seeking fertility should not receive testosterone therapy, as it suppresses spermatogenesis and can cause azoospermia 1, 2
• The suppressive effect on sperm production may be reversible short-term but potentially has long-term impacts that should be discussed with patients interested in future fertility 1

Pregnancy and Transfer Risk

• Pregnancy is an absolute contraindication—testosterone gel can cause virilization of female fetuses through direct exposure or skin-to-skin transfer from treated male partners 3
• Women who are pregnant must avoid contact with unwashed or unclothed application sites on men using topical testosterone 3

Relative Contraindications and High-Risk Situations

Prostate Conditions

• Severe lower urinary tract symptoms (LUTS) warrant caution, though testosterone therapy does not significantly worsen LUTS or prostate volume in men with mild-to-moderate symptoms 1, 4
• Men with benign prostatic hyperplasia (BPH) should be monitored for worsening signs and symptoms, though multiple studies show safety in this population except with severe baseline symptoms 1, 4, 3

Cardiovascular and Hematologic Concerns

• Recent cardiovascular events (myocardial infarction, stroke) represent a relative contraindication, as patients with recent events were typically excluded from trials, limiting safety data 2
• Baseline hematocrit >54% requires intervention before initiating therapy, as testosterone increases red blood cell mass and venous thromboembolism risk 3

Sleep Disorders

• Severe untreated obstructive sleep apnea may be exacerbated by testosterone therapy, though combined CPAP and testosterone gel showed better outcomes than CPAP alone in one study 1, 2

Organ Dysfunction

• Renal insufficiency requires caution due to fluid retention risk 2
• Hepatic disease necessitates caution, particularly with oral testosterone formulations which have been associated with hepatotoxicity (intramuscular and transdermal preparations appear safer) 2

Acute Illness

• Active acute illness is a contraindication—testosterone testing and therapy should be avoided during acute medical conditions 2

Special Populations and Emerging Evidence

Prostate Cancer Survivors

• While historically contraindicated, recent high-quality evidence challenges this absolute prohibition 1, 2
• The TRAVERSE trial (2025) showed no difference in prostate cancer incidence between testosterone and placebo groups at 33-month follow-up 1, 2
• For prostate cancer survivors, safety data remain limited, and meta-analyses suggest no increased recurrence risk, though evidence quality is poor 1
• Testosterone therapy should be avoided in advanced prostate cancer, but may be considered in select men definitively treated for localized disease with thorough counseling about unknown long-term effects 1, 5
• Men with prostate cancer on active surveillance or androgen deprivation therapy should not receive testosterone 2

Inappropriate Use

• Eugonadal men (men with normal testosterone levels) should not receive testosterone therapy 1
• Age-related hypogonadism has not established safety and efficacy data 3
• Testosterone should not be used for weight reduction, cardiometabolic enhancement, or to improve cognition, vitality, and physical strength in aging men 1

Monitoring Requirements Before Initiation

Mandatory Baseline Assessments

• PSA testing and digital rectal examination in men over 40 years before starting therapy to exclude prostate cancer 2, 4
• If PSA is elevated, obtain a second test to rule out spurious elevation 4
• Hematocrit/hemoglobin measurement at baseline 4, 3
• Cardiovascular risk factor assessment 4
• Confirm diagnosis with morning serum testosterone measured on at least two separate days, both below normal range 3

Critical Monitoring During Treatment

• Follow-up at 3 months when sexual symptoms typically improve, then every 3-6 months for the first year, then annually 2
• Hematocrit >54% requires dose reduction, temporary discontinuation, or phlebotomy in high-risk cases 1, 3
• PSA monitoring with biopsy indicated for PSA increase of ≥1.0 ng/mL in any year, or 0.7-0.9 ng/mL with further increase in 3-6 months 2

Critical Safety Warnings

Secondary Exposure Prevention

• Children and women must avoid contact with unwashed or unclothed application sites, as secondary exposure has caused virilization in children (enlarged genitalia, pubic hair development, increased erections, aggressive behavior, advanced bone age) 3
• Patients must wash hands immediately after application and cover application sites with clothing after gel dries 3
• Wash application sites thoroughly with soap and water before any anticipated skin-to-skin contact 3

Drug Interactions

• PDE5 inhibitors are contraindicated with nitrates due to dangerous blood pressure decreases—relevant when combining testosterone with erectile dysfunction treatment 2