Testosterone Cypionate Dosing for Male Hypogonadism
Standard Starting Dose
For adult males with confirmed hypogonadism, start testosterone cypionate at 50-100 mg intramuscularly every week, or alternatively 100-200 mg every 2 weeks, with the FDA-approved range being 50-400 mg every 2-4 weeks. 1, 2 However, weekly dosing of 50-100 mg provides significantly more stable testosterone levels and reduces the risk of adverse effects compared to biweekly administration. 2
Dosing Regimen Selection
Weekly dosing (50-100 mg) is strongly preferred over biweekly dosing because it minimizes fluctuations in serum testosterone levels, which reduces erythrocytosis risk and potentially cardiovascular complications. 2
The evidence demonstrates that:
- 200 mg every 2 weeks effectively suppresses elevated LH and FSH to normal range while maintaining physiologic testosterone levels 3
- Biweekly injections of 200 mg cause wide fluctuations, with testosterone peaking 2-5 days post-injection (often reaching supraphysiologic levels) and returning to baseline by days 13-14 4
- Many patients achieve androgen concentrations above normal range between days 2-7 with 200 mg biweekly dosing, with some reaching several times the upper limit of normal 4
Administration Route and Site
Administer deep intramuscular injection into the gluteal muscle, though subcutaneous injection is an equally effective and increasingly preferred alternative. 1, 5
Subcutaneous administration offers several advantages:
- Achieves therapeutic testosterone levels equivalent to intramuscular administration with doses of 50-150 mg weekly 5
- Effective across a wide BMI range (19.0-49.9 kg/m²) 5
- Patients demonstrate marked preference for subcutaneous over intramuscular injections (20 of 22 patients in one study) 5
- Can be self-administered in the thigh, improving patient autonomy 2
For intramuscular injections, use 21-23 gauge, 1-1.5 inch needles, with longer needles (1.5 inch) for gluteal injections and shorter needles (1 inch) potentially sufficient for thigh injections in leaner patients. 6
Target Testosterone Levels and Monitoring
Target mid-normal testosterone levels of 450-600 ng/dL, measured midway between injections (days 5-7 for weekly dosing, days 7-10 for biweekly dosing). 6, 2, 7
Critical monitoring parameters:
- Measure testosterone levels 2-3 months after treatment initiation or any dose change 6, 2
- Once stable, monitor every 6-12 months 6, 2
- Monitor hematocrit at each visit—withhold treatment if >54% and consider phlebotomy 6, 7
- Monitor PSA in men over 40 years, with urologic referral if PSA increases >1.0 ng/dL in first 6 months or >0.4 ng/dL per year thereafter 6
Dose Adjustment Algorithm
If testosterone levels are measured midway between injections:
- If levels <450 ng/dL AND clinical response is suboptimal: increase dose by 25-50 mg per injection 6
- If levels 450-600 ng/dL with adequate clinical response: continue current dose 6
- If levels >1000 ng/dL: reduce dose by approximately 50% regardless of symptoms, as supraphysiologic levels increase erythrocytosis and cardiovascular risk 6
Critical Safety Considerations
Injectable testosterone carries significantly higher risk of erythrocytosis compared to transdermal preparations—43.8% with intramuscular injections versus 15.4% with transdermal patches. 2 This occurs due to supraphysiologic peak levels and fluctuating testosterone concentrations. 2
Testosterone therapy is absolutely contraindicated in men seeking fertility preservation, as it causes azoospermia. 6, 7 For these patients, gonadotropin therapy (hCG plus FSH) is mandatory. 6
Additional contraindications include:
- Active or treated male breast cancer 6, 7
- Recent cardiovascular events within past 3-6 months 7
- Hematocrit >54% 6
- Untreated severe obstructive sleep apnea 6
Common Pitfalls to Avoid
Never draw testosterone levels at peak (days 2-5) or trough (days 13-14), as this leads to inappropriate dose adjustments. 6 Peak measurements show supraphysiologic levels that don't reflect average exposure, while trough measurements may prompt unnecessary dose escalation. 6
Never continue supraphysiologic dosing (>400 mg every 2 weeks or >200 mg weekly) even if the patient reports feeling well, as this dramatically increases adverse event risk without additional benefit. 6
Never start testosterone without confirming the patient does not desire fertility, as suppression of spermatogenesis can be prolonged even after discontinuation. 6