Testosterone Enanthate: Uses, Dosage, and Side Effects
Primary Indication
Testosterone enanthate is FDA-approved exclusively for replacement therapy in men with hypogonadism—a condition characterized by low serum testosterone levels accompanied by symptoms such as diminished libido, erectile dysfunction, decreased energy, reduced muscle mass, or depressed mood. 1
The medication treats both primary hypogonadism (testicular failure from conditions like cryptorchidism, orchitis, or orchidectomy) and secondary hypogonadism (pituitary-hypothalamic dysfunction from tumors, trauma, or radiation). 1
Dosing Recommendations
Standard Intramuscular Dosing
Start with 50-100 mg weekly via intramuscular injection, targeting mid-normal testosterone levels of 450-600 ng/dL. 2, 3
Alternative regimens include:
- 100-200 mg every 2 weeks (traditional approach, though causes more fluctuation) 2, 3
- 200 mg every 2 weeks or 300 mg every 3 weeks effectively suppresses elevated LH/FSH to normal range 4
Weekly dosing of 50-100 mg provides superior testosterone stability compared to biweekly administration and is the preferred approach. 2, 3 Peak serum levels occur 2-5 days after injection, with return to baseline by days 10-14, creating a "roller coaster" effect with less frequent dosing. 5
Maximum Safe Dosing
The maximum recommended weekly dose is 100-200 mg; doses exceeding 200 mg weekly significantly increase erythrocytosis risk and are considered supraphysiologic. 2 Research doses of 600 mg weekly cause substantial HDL reduction and are not appropriate for clinical use. 2
Subcutaneous Alternative
Subcutaneous administration at 50-150 mg weekly achieves equivalent therapeutic levels to intramuscular injection with less discomfort and easier self-administration. 3, 6, 7 This route is increasingly preferred for patient convenience. 3
Monitoring Protocol
Initial Monitoring
Measure testosterone levels at 2-3 months after initiation, checking midway between injections and targeting 450-600 ng/dL. 2, 3 This mid-cycle measurement captures representative values rather than artificial peaks or troughs. 3
Ongoing Surveillance
Once stable levels are achieved, monitor every 6-12 months: 3
- Testosterone levels (target 450-600 ng/dL)
- Hematocrit/hemoglobin at each visit (withhold therapy if hematocrit exceeds 54%) 2
- PSA and digital rectal examination 3
- Lipid profile periodically 3
- Cardiovascular symptoms assessment 8
Side Effects and Risks
Common and Serious Adverse Effects
Erythrocytosis represents the most significant dose-dependent risk, occurring in up to 44% of patients on injectable testosterone compared to 3-18% with transdermal formulations. 5 This requires regular hematocrit monitoring. 2
Additional side effects by frequency: 5
Common:
- Testicular atrophy or infertility (common, especially in young men; usually reversible with cessation) 5
- Acne or oily skin (infrequent) 5
- Injection site reactions (rare with injections, unlike 66% rate with patches) 5
Infrequent but Important:
- Sleep apnea (infrequent) 5
- Gynecomastia (rare, usually reversible) 5
- Fluid retention (rarely clinically significant) 5
- Benign prostatic hyperplasia (rarely clinically significant) 5
Cardiovascular Considerations
Existing evidence suggests testosterone has a neutral or possibly beneficial effect on cardiovascular disease, contrary to historical concerns. 5 Studies show men with higher testosterone levels may have reduced cardiovascular risk, and testosterone therapy has not demonstrated increased incidence of myocardial infarction, stroke, or angina. 5
However, injectable testosterone may carry greater cardiovascular risk than transdermal preparations due to fluctuating testosterone levels. 3 Do not initiate therapy for 3-6 months following recent cardiovascular events. 8
Lipid Profile Effects
Physiologic replacement doses show no change or minimal reduction in HDL cholesterol in most studies, with total cholesterol often reduced. 5, 8 Only supraphysiologic doses (600 mg weekly) cause significant HDL reduction. 2 Oral nonaromatizable androgens adversely affect lipids, but standard testosterone enanthate at replacement doses maintains neutral lipid effects. 8
Prostate Cancer Controversy
The relationship between testosterone therapy and prostate cancer remains controversial with unknown level of risk, requiring long-term monitoring. 5 Theoretical concerns exist regarding possible stimulation of prostate cancer, though definitive evidence is lacking. 5
Critical Safety Caveats
Never prescribe 17-alpha-alkylated androgens (methyltestosterone) due to hepatotoxicity. 8 Hepatotoxicity is limited to oral agents, which are infrequently used. 5
Counsel all patients on testosterone therapy regarding lifestyle modifications including weight loss, physical activity, and smoking cessation to optimize cardiovascular health and lipid profiles. 8 High BMI coupled with low testosterone increases cardiovascular event risk. 8
Adjust dosing to use the minimal amount necessary to achieve mid-normal testosterone levels (450-600 ng/dL), as supraphysiologic levels increase adverse event risk without additional benefit. 2, 8