What is the best treatment for hypogonadism?

Best Treatment for Hypogonadism

Testosterone replacement therapy (TRT) is the first-line treatment for hypogonadism, with intramuscular testosterone formulations recommended as the initial treatment due to their established efficacy and lower cost compared to transdermal options. 1

Diagnosis Confirmation

Before initiating treatment, diagnosis should be confirmed with:

• Morning total testosterone levels < 300 ng/dL on at least two separate occasions 1
• Comprehensive hormonal evaluation including LH and FSH measurements 1
• Assessment of baseline hemoglobin, hematocrit, and cardiovascular risk factors 1

Treatment Algorithm

First-Line Treatment: Testosterone Replacement Therapy (TRT)

1. Intramuscular testosterone formulations

   • Recommended as initial treatment due to:
     • Similar clinical effectiveness to other formulations
     • Considerably lower cost compared to transdermal options
     • Established efficacy for improving sexual function 1
   • Monitoring: Testosterone levels should be measured midway between injections 1

2. Transdermal preparations (gels and patches)

   • Alternative first-line option, especially when stable day-to-day levels are preferred 1
   • Application site for testosterone 2% gel: front and inner thighs 2
   • Low volume application may be preferred by some patients 2

3. Dose adjustment based on pre-dose morning testosterone levels:

   • 750 ng/dL: Decrease daily dose by 20-25%

   • 350-750 ng/dL: No change
   • <350 ng/dL: Increase daily dose by 20-25% 1

Alternative Treatments (When Fertility Preservation is Desired)

1. Gonadotropin therapy

   • Start with human chorionic gonadotropin (hCG) alone
   • Add follicle-stimulating hormone (FSH) if needed
   • Treatment of choice when fertility preservation is required 1, 3

2. Clomiphene citrate (CC)

   • Off-label use for hypogonadism with fertility preservation
   • Increases endogenous testosterone production 1, 3
   • Note: Data supporting efficacy on hypogonadal symptoms are insufficient 3

3. Selective estrogen receptor modulators (SERMs)

   • Alternative for functional central hypogonadism
   • Can significantly increase testosterone levels 1, 3
   • Use is off-label and should not be routine clinical practice 3

Monitoring Protocol

• Testosterone levels: After starting treatment and every 6-12 months
• Target level: Mid-normal range (450-600 ng/dL) 1
• Hemoglobin/hematocrit: Discontinue if Hct >54% 1
• PSA: Monitor according to guidelines; consider discontinuation if significant increase 1, 4
• Efficacy assessment: Evaluate symptom improvement after 3-6 months 1

Contraindications and Precautions

Absolute Contraindications

• Prostate cancer
• Breast cancer
• Desire for near-term fertility
• Severe sleep apnea
• Uncontrolled heart failure
• Recent cardiovascular events 1

Relative Contraindications

• History of hepatocellular carcinoma
• Thrombosis
• Other cardiovascular risk factors 1

Common Adverse Effects

• Erythrocytosis (dose-dependent: 2.8-17.9%)
• Suppression of spermatogenesis
• Peripheral edema
• Emotional lability 1, 4, 5
• Skin reactions (with transdermal preparations) 4, 2

Special Considerations

1. Fertility concerns:

   • TRT suppresses spermatogenesis and can cause oligospermia or azoospermia 1, 6
   • For men interested in current or future fertility, consider gonadotropins, SERMs, or aromatase inhibitors 1, 6, 7

2. Lifestyle modifications:

   • Weight loss through low-calorie diets and physical activity can reverse obesity-associated secondary hypogonadism 1
   • Consider as first-line approach for metabolic benefits
   • Combining lifestyle changes with TRT may yield better outcomes in symptomatic patients 1

3. Geriatric patients:

   • May be at increased risk for developing prostatic hypertrophy and carcinoma 5
   • Careful monitoring required in this population 8

Treatment Efficacy

• TRT provides small but significant improvements in global sexual function and erectile function 1
• Small improvements in quality of life 1
• Limited or no effect on physical functioning, depressive symptoms, energy/vitality, and cognition 1
• All approved testosterone replacement methods, when used according to recommendations, can restore normal serum testosterone concentrations and relieve symptoms in most hypogonadal men 6