Testosterone Replacement Therapy for Secondary Hypogonadism
Testosterone replacement therapy (TRT) is appropriate for secondary hypogonadism when symptoms are present and testosterone deficiency is confirmed through laboratory testing, with special considerations for fertility preservation when needed. 1
Diagnosis and Assessment
- Secondary hypogonadism must be confirmed through both persistent specific symptoms (decreased libido, erectile dysfunction, fatigue) and laboratory confirmation of decreased morning total testosterone levels 1
- Assessment should include:
- Evaluation for pituitary disorders, surgical history, comorbidities, and medications affecting the hypothalamic-pituitary-gonadal axis 1
- Morning total testosterone concentration drawn between 8-10 AM 1
- Free testosterone level by equilibrium dialysis and sex hormone-binding globulin level, especially in obese patients 1
- Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements to confirm secondary (pituitary-hypothalamic) hypogonadism 1
Treatment Approach
For Patients NOT Seeking Fertility
- TRT is the first-line treatment for symptomatic secondary hypogonadism when fertility is not an immediate concern 1
- TRT is strongly recommended as first-line treatment for hypogonadal patients with mild erectile dysfunction 1
- For more severe erectile dysfunction, consider combination of TRT with phosphodiesterase type 5 inhibitors 1
For Patients Seeking Fertility
- TRT is contraindicated in men seeking fertility as it suppresses spermatogenesis 1
- Gonadotropin therapy is the standard treatment for secondary hypogonadism when fertility preservation is desired 1, 2
- Combined human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) therapy provides optimal outcomes for fertility 1, 2
Treatment Options
Testosterone Formulations
- Multiple testosterone formulations are available, with selection based on clinical characteristics, availability, and patient preferences 1
- Transdermal preparations (gel, patch) provide relatively stable testosterone levels but may have variable absorption and potential for transfer to others 1
- Intramuscular injections offer less frequent administration but can cause fluctuating testosterone levels 1
- Implantable pellets provide long-term treatment but require a procedure for implantation 1
Gonadotropin Therapy (for fertility preservation)
- Combination of hCG and FSH for 12-24 months promotes testicular growth and spermatogenesis 2
- Success rates: approximately 80% for spermatogenesis and 50% for pregnancy 2
- Gynecomastia is the most common side effect due to increased estradiol secretion 2
Special Considerations
Obesity-Related Secondary Hypogonadism
- Functional hypogonadism commonly correlates with obesity and metabolic disorders 1
- Weight loss through diet and physical activity can reverse obesity-associated secondary hypogonadism 1
- Lifestyle modifications should be recommended but may yield modest testosterone increases (1-2 nmol/L) 1
- Consider combining lifestyle changes with TRT for better outcomes in symptomatic patients 1
Contraindications and Cautions
- Active or treated male breast cancer (absolute contraindication) 1
- Desire for fertility in the near future 1
- Prostate cancer (use with caution, especially in advanced disease) 1
- Severe lower urinary tract symptoms (use with caution) 1
- Cardiovascular disease (consider individual risk assessment) 1
Monitoring
- Follow-up monitoring should include:
Pitfalls to Avoid
- Don't use TRT in eugonadal men (strong recommendation) 1
- Don't use TRT to reduce weight or enhance cardiometabolic status as primary goal 1
- Don't use TRT to improve cognition, vitality, or physical strength in aging men without documented hypogonadism 1
- Don't test testosterone levels during acute illness as they may be falsely low 1
- Don't overlook fertility concerns when initiating TRT in men of reproductive age 1