Testosterone Initiation Therapy for Confirmed Hypogonadism
For patients with confirmed hypogonadism, the recommended first-line treatment depends on etiology, with human chorionic gonadotropin (hCG) injections (500-2500 IU, 2-3 times weekly) being the preferred first-line therapy for hypogonadotropic hypogonadism when fertility preservation is desired, while testosterone replacement therapy is recommended for primary hypogonadism or when fertility is not a concern. 1, 2
Diagnostic Confirmation Before Initiation
Before starting any treatment:
- Confirm low testosterone with two separate morning measurements below 300 ng/dL
- Document presence of symptoms (reduced energy, fatigue, decreased libido, erectile dysfunction)
- Measure luteinizing hormone (LH) levels to determine etiology (primary vs. secondary hypogonadism)
- Rule out contraindications to therapy 2
Treatment Algorithm Based on Hypogonadism Type and Fertility Concerns
For Hypogonadotropic Hypogonadism (Secondary)
If fertility preservation is desired:
If fertility is not a concern:
- Testosterone replacement therapy (see formulations below)
For Primary Hypogonadism:
- Testosterone replacement therapy (see formulations below) 2
Testosterone Replacement Therapy Formulations
Oral Testosterone Undecanoate:
- Starting dose: 200 mg twice daily with food (morning and evening)
- Adjust to minimum 100 mg once daily up to maximum 400 mg twice daily
- Monitor testosterone levels 3-5 hours after morning dose 4
Topical Gels/Solutions:
- Preferred initial option for older men
- Advantages: Steady hormone levels, ease of application
- Disadvantages: Risk of transfer to women/children, skin irritation 2
Intramuscular Injections:
- Testosterone cypionate or enanthate every 1-2 weeks
- Advantages: Lower cost, less frequent administration
- Disadvantages: Fluctuating hormone levels, injection discomfort 2
Monitoring and Dose Adjustments
- Target testosterone levels: 450-600 ng/dL (mid-normal range)
- Check testosterone levels 4-6 weeks after initiation and every 3-6 months thereafter
- Follow-up visits: 1-2 months after initiation, then every 3-6 months, yearly if stable
- Monitor for adverse effects, particularly:
Important Contraindications
Testosterone therapy is contraindicated in:
- Prostate cancer or male breast cancer
- Desire for fertility in the near future
- Severe obstructive sleep apnea
- Uncontrolled congestive heart failure
- Hematocrit >54%
- Active alcohol use disorder 2
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 2
Special Considerations for Fertility
- Exogenous testosterone administration suppresses spermatogenesis and can cause oligospermia or azoospermia
- Recovery after cessation may take months or even years
- For men interested in current or future fertility, avoid exogenous testosterone therapy and consider alternatives like hCG 1, 5
Cardiovascular Risk
- Testosterone therapy can cause blood pressure increases that may increase risk of major adverse cardiovascular events
- Before initiating therapy, consider baseline cardiovascular risk and ensure blood pressure is adequately controlled
- Periodically monitor for and treat new-onset hypertension or exacerbations of pre-existing hypertension 4
The choice of treatment should be guided by the specific type of hypogonadism, fertility desires, patient preference, and risk profile, with careful monitoring for efficacy and adverse effects.