What is the recommended treatment regimen for testosterone therapy in individuals with hypogonadism?

Testosterone Therapy for Hypogonadism

For individuals with confirmed hypogonadism, testosterone replacement therapy should be initiated with a starting dose of testosterone gel 1.62% at 40.5 mg applied topically once daily in the morning to the shoulders and upper arms. 1, 2

Diagnosis Confirmation

• Measure morning total testosterone concentration between 8 AM and 10 AM on at least two separate days to confirm hypogonadism 1, 3
• Measure free testosterone by equilibrium dialysis and sex hormone-binding globulin, especially in obese patients 1, 3
• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1, 3
• For secondary hypogonadism, additional tests include serum prolactin, iron saturation, pituitary function testing, and MRI of sella turcica 3

Treatment Options

Topical Formulations (First-Line)

• Testosterone gel 1.62%: Start with 40.5 mg (2 pump actuations or a single 40.5 mg packet) applied once daily in the morning to clean, dry, intact skin of shoulders and upper arms 1, 2
• Dose adjustment: Can be adjusted between 20.25 mg (minimum) and 81 mg (maximum) based on pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment 2
• Advantages: Provides stable day-to-day testosterone levels, fewer skin reactions than patches, higher patient satisfaction 4, 5
• Important safety note: Wash hands immediately after application and cover application site with clothing after gel has dried to prevent secondary exposure 2

Injectable Formulations

• Intramuscular testosterone injections (cypionate or enanthate): Administered every 2-3 weeks 1
• Peak serum levels occur 2-5 days after injection, with return to baseline usually observed 10-14 days after injection 1
• For patients receiving testosterone injections, levels should be measured midway between injections, targeting a mid-normal value (500-600 ng/dL) 1
• Testosterone undecanoate injections (newer formulation): One injection every 3 months, providing more stable serum testosterone levels 4

Alternative Therapies (For Fertility Preservation)

• For men desiring fertility preservation, testosterone therapy is contraindicated as it suppresses spermatogenesis 6, 7
• Alternative options include:
  • Human chorionic gonadotropin (hCG) 8
  • Combination of hCG and FSH (for secondary hypogonadism) 8
  • Selective estrogen receptor modulators (SERMs) like clomiphene citrate (off-label) 7, 9

Monitoring and Follow-up

• Measure testosterone levels 2-3 months after treatment initiation and after any dose adjustment 1, 3
• Once stable levels are achieved, monitor every 6-12 months 1, 3
• Monitor for potential adverse effects:
  • Erythrocytosis (elevated hematocrit) - higher risk with injectable forms 1
  • PSA elevation in men over 40 years 1, 3
  • Fluid retention, especially in patients with cardiac, renal, or hepatic disease 2
  • Emotional lability, hypertension, and contact dermatitis 3

Important Considerations

• Do not use testosterone therapy in eugonadal men 6
• Contraindications include prostate cancer, breast cancer, uncontrolled congestive heart failure, severe lower urinary tract symptoms, and erythrocytosis 3, 2
• For obesity-associated secondary hypogonadism, weight loss through low-calorie diets and physical activity can improve testosterone levels 6, 3
• Consider discontinuing therapy after 3-6 months if target testosterone levels are achieved but symptoms don't improve 3
• Long-term efficacy and safety data are limited, particularly for men aged 18 to 50 years with hypogonadism 6

Treatment Algorithm

1. Confirm diagnosis with repeated morning testosterone measurements
2. Determine primary vs. secondary hypogonadism with LH/FSH levels
3. Assess fertility desires:
   • If fertility desired: Use gonadotropin therapy (hCG ± FSH) 8
   • If fertility not a concern: Proceed with testosterone replacement therapy 1
4. Select formulation based on patient preference and clinical factors:
   • First choice: Testosterone gel 1.62% (40.5 mg daily) for stable levels and convenience 1, 2
   • Alternative: Intramuscular injections if cost is a concern 1
5. Monitor testosterone levels at 2-3 months, then every 6-12 months once stable 1, 3
6. Adjust dose based on testosterone levels and symptom response 2