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

Treatment for Symptomatic Low Testosterone (Hypogonadism)

Testosterone replacement therapy (TRT) is the recommended treatment for men with symptomatic hypogonadism who do not desire fertility preservation, while clomiphene citrate is preferred for men who wish to maintain fertility. 1

Diagnostic Confirmation

Before initiating treatment:

• Confirm hypogonadism with morning serum testosterone measurements on at least two separate days showing levels below normal range 2, 3
• Ensure symptoms are present (decreased sexual desire/libido, erectile dysfunction, fatigue, etc.) 4
• Consider measuring sex hormone-binding globulin in men with total testosterone levels near the lower limit 4

Treatment Options

1. For Men Without Fertility Concerns: Testosterone Replacement Therapy

TRT provides:

• Moderate-certainty evidence for small but significant improvements in sexual function (SMD 0.35) and erectile function (SMD 0.27) 1
• Low-certainty evidence for improvements in quality of life (SMD 0.33 lower on AMS scale) and energy/vitality (SMD 0.17) 1
• Small improvements in depressive symptoms (SMD 0.19 lower) 1

Dosing and Administration:

• Starting dose: 40.5 mg testosterone gel (1.62%) applied topically once daily to shoulders and upper arms 2, 3
• Dose adjustment: Based on pre-dose morning serum testosterone levels at 14 and 28 days after starting treatment 2, 3

  • 750 ng/dL: Decrease dose by 20.25 mg

  • 350-750 ng/dL: Maintain current dose
  • <350 ng/dL: Increase dose by 20.25 mg
• Target testosterone levels: 450-600 ng/dL 1

Monitoring:

• Check testosterone levels 4-6 weeks after treatment initiation and every 3-6 months thereafter 1
• Monitor hematocrit/hemoglobin every 3-6 months (discontinue TRT if hematocrit >54%) 1

2. For Men With Fertility Concerns: Clomiphene Citrate

• Works as a selective estrogen receptor modulator (SERM) to increase endogenous testosterone production 1
• Preserves fertility and may improve sperm parameters, unlike exogenous testosterone 1
• Suitable for young men with hypogonadism, patients with secondary hypogonadism, and men with low testosterone accompanied by low/normal LH levels 1

Contraindications to TRT

• Prostate cancer
• Male breast cancer
• Desire for fertility in the near future
• Severe obstructive sleep apnea
• Uncontrolled congestive heart failure
• Hematocrit >54% 1

Potential Adverse Effects of TRT

• Suppression of spermatogenesis (major concern for men desiring fertility)
• Erythrocytosis (higher risk with intramuscular injections at 43.8% vs. transdermal at 5.5-15.4%)
• Peripheral edema
• Emotional lability
• Potential cardiovascular effects 1

Special Considerations

1. Age-related hypogonadism: Safety and efficacy of testosterone gel in men with "age-related hypogonadism" have not been established 2, 3

2. Diabetic patients: Testosterone therapy should only be considered in diabetic men with confirmed hypogonadism characterized by symptoms like decreased sexual desire and erectile dysfunction 1

3. Administration route: Consider patient preference for topical vs. injectable formulations 1

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
• Using testosterone for "age-related hypogonadism" without structural or genetic etiology 1