What is the primary treatment for hypogonadism (low testosterone)?

Treatment for Low Testosterone (Hypogonadism)

Testosterone replacement therapy (TRT) is the primary treatment for hypogonadism, specifically indicated for men with confirmed testosterone deficiency due to primary hypogonadism or hypogonadotropic hypogonadism. 1, 2

Diagnostic Confirmation

Before initiating treatment:

• Confirm diagnosis with morning testosterone measurements on at least two separate days showing levels below normal range 3, 1
• Determine the cause of hypogonadism (primary vs. secondary)
• Rule out contraindications to therapy

Treatment Options

FDA-Approved Formulations

1. Transdermal Preparations

   • Testosterone gel 1.62% applied daily to shoulders and upper arms
   • Starting dose: 40.5 mg testosterone (2 pump actuations or single 40.5 mg packet)
   • Dose can be adjusted between 20.25-81 mg based on serum levels 1
   • Advantages: stable hormone levels, ease of application
   • Caution: risk of secondary exposure to women and children

2. Intramuscular Injections

   • Testosterone cypionate or enanthate
   • Typically administered every 1-4 weeks
   • Advantages: cost-effective, reliable absorption
   • Disadvantages: fluctuating testosterone levels, injection discomfort 2, 4

3. Other Formulations

   • Buccal, nasal, and subdermal preparations 5
   • Oral testosterone undecanoate (newer formulation with improved bioavailability) 6

Monitoring and Dose Adjustment

• Check testosterone levels 4-6 weeks after treatment initiation 3
• Follow-up every 3-6 months initially, then yearly if stable 3
• Target testosterone levels: 450-600 ng/dL (mid-normal range) 3
• Adjust dose according to serum levels and symptom response (see table below) 1

Pre-Dose Morning Testosterone	Dose Adjustment
>750 ng/dL	Decrease daily dose by 20.25 mg
350-750 ng/dL	No change
<350 ng/dL	Increase daily dose by 20.25 mg

Expected Benefits

TRT provides:

• Small but significant improvements in sexual function (moderate-certainty evidence) 7, 3
• Small improvements in quality of life (low-to-moderate certainty evidence) 7
• Potential improvements in bone mineral density and muscle strength (low-certainty evidence) 3
• Little to no effect on physical functioning, energy/vitality, or cognition 7

Contraindications

TRT is contraindicated in men with:

• Prostate cancer
• Male breast cancer
• Desire for fertility in the near future
• Severe obstructive sleep apnea
• Uncontrolled congestive heart failure
• Hematocrit >54% 3
• Active alcohol use disorder (particularly for oral alkylated testosterone) 3

Potential Adverse Effects

• Erythrocytosis (dose-dependent: 2.8-17.9%)
• Suppression of spermatogenesis
• Peripheral edema
• Emotional lability
• Potential cardiovascular effects (long-term safety uncertain) 7, 3

Important Considerations

• TRT is specifically indicated for documented hypogonadism, not for "age-related hypogonadism" or "late-onset hypogonadism" where safety and efficacy have not been established 1
• Application site and dose are not interchangeable between different testosterone products 1
• Long-term efficacy and safety data beyond 1 year are limited 7
• For men desiring fertility preservation, alternative approaches that stimulate endogenous testosterone (selective estrogen receptor modulators, gonadotropins, aromatase inhibitors) may be considered 8

Common Pitfalls to Avoid

• Diagnosing hypogonadism based on a single testosterone measurement
• Failing to measure free testosterone in obese patients
• Overlooking secondary causes of hypogonadism
• Initiating therapy without proper baseline evaluation
• Not monitoring for adverse effects, particularly hematocrit elevation and blood pressure increases
• Using testosterone for "age-related hypogonadism" without structural or genetic etiology 3