Testosterone Replacement Therapy for Male Hypogonadism

Diagnostic Criteria

• The American College of Endocrinology recommends confirming biochemical hypogonadism with two separate morning total testosterone measurements <300 ng/dL, and measuring LH and FSH to distinguish primary from secondary hypogonadism 1
• Primary symptoms justifying treatment include diminished libido and erectile dysfunction, while secondary symptoms include diminished vitality, though evidence for improvement is weaker 1, 2

Treatment Guidelines

• The Endocrine Society recommends starting with 50-75 mg subcutaneous testosterone cypionate or enanthate weekly, adjusting based on week 6 trough levels, with a target trough testosterone of 500-600 ng/dL 1
• Subcutaneous testosterone offers more stable serum testosterone levels with smaller peak-trough fluctuations compared to IM injections every 2-4 weeks 3

Monitoring and Follow-up

• The American Urological Association recommends measuring testosterone at 2-3 months after initiation or dose change, and monitoring hematocrit periodically, withholding treatment if >54% 1, 4
• Monitor PSA in men >40 years, and discontinue treatment at 12 months if no improvement in sexual function 1, 4

Expected Clinical Outcomes

• The American College of Physicians recommends discussing realistic expectations upfront, including small but significant improvements in sexual function and libido, and modest improvements in quality of life 5, 1
• Testosterone replacement therapy has little to no effect on physical functioning, energy/vitality, depressive symptoms, or cognition 5, 1

Special Populations

• For men with secondary hypogonadism who may desire future fertility, the European Association of Urology recommends first-line gonadotropin therapy to stimulate endogenous testosterone production and preserve spermatogenesis, as testosterone is absolutely contraindicated if fertility is desired 1