What is the initial step to start testosterone replacement therapy for hypogonadism?

Starting Testosterone Therapy for Hypogonadism

The initial step to start testosterone replacement therapy for hypogonadism is to confirm the diagnosis with two morning total testosterone measurements below the normal range, along with symptoms consistent with hypogonadism. 1

Diagnostic Confirmation

Before initiating testosterone therapy, follow these steps:

1. Confirm low testosterone with laboratory testing:

   • Measure morning total testosterone levels on at least two separate days 2
   • Both measurements must be below the normal range
   • Consider free testosterone or sex hormone-binding globulin levels in patients with borderline total testosterone 3

2. Document hypogonadism symptoms:

   • Sexual symptoms (decreased libido, erectile dysfunction)
   • Physical symptoms (fatigue, decreased energy, reduced muscle mass)
   • Psychological symptoms (depressed mood, cognitive issues)

3. Determine hypogonadism type:

   • Primary hypogonadism: Low testosterone with high FSH/LH
   • Secondary hypogonadism: Low testosterone with normal/low FSH/LH

4. Rule out contraindications:

   • Active prostate or breast cancer 2
   • Hematocrit >50% 3
   • Severe untreated sleep apnea
   • Uncontrolled heart failure
   • Recent cardiovascular events (within 3-6 months) 3
   • Desire for fertility in near future 1

Pre-Treatment Evaluation

Before starting therapy:

1. Baseline laboratory tests:

   • Complete hormone panel (total testosterone, free testosterone, LH, FSH)
   • Hematocrit/hemoglobin
   • PSA (in men >40 years)
   • Liver function tests
   • Lipid profile (if cardiovascular risk factors) 3

2. Physical examination:

   • Digital rectal examination (in men >40 years) 1
   • BMI and waist circumference 1
   • Blood pressure

3. Address modifiable factors:

   • Evaluate for medications that may interfere with testosterone production 1
   • Address obesity and metabolic disorders 1
   • Consider lifestyle modifications (weight loss, exercise) 3

Treatment Selection

The recommended initial approach:

1. Starting dose:

   • Topical gel: 40.5 mg of testosterone (2 pump actuations) applied once daily in the morning to shoulders and upper arms 2
   • Injectable testosterone: 50-100 mg weekly (testosterone cypionate/enanthate) 3

2. Application instructions for gel formulations:

   • Apply to clean, dry, intact skin of shoulders and upper arms only
   • Do not apply to abdomen, genitals, chest, armpits, or knees
   • Wash hands thoroughly after application
   • Cover application site with clothing once dry
   • Avoid swimming/showering for at least 2 hours after application 2

Monitoring and Follow-up

1. Initial follow-up:

   • Check testosterone levels at approximately 14 days and 28 days after starting treatment 2
   • Adjust dose based on pre-dose morning testosterone levels:
     • If >750 ng/dL: Decrease dose
     • If 350-750 ng/dL: Maintain dose
     • If <350 ng/dL: Increase dose 2

2. Regular monitoring:

   • Testosterone levels
   • Hematocrit (discontinue if >54%)
   • PSA (consider biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year)
   • Evaluate for symptom improvement 3

Important Considerations and Pitfalls

1. Fertility concerns:

   • Testosterone therapy is contraindicated in men seeking fertility 1
   • For secondary hypogonadism with fertility desires, consider gonadotropin therapy (hCG) instead 1
   • Recovery of spermatogenesis after testosterone cessation may take months or years 1

2. Age-related considerations:

   • FDA has not approved testosterone for "age-related hypogonadism" 2
   • Evidence for benefits in older men with age-related decline is limited 1

3. Safety monitoring:

   • Watch for polycythemia (most common adverse effect)
   • Monitor for sleep apnea symptoms
   • Be alert for signs of cardiovascular events 3

4. Target testosterone levels:

   • Aim for mid-normal range (450-600 ng/dL) 3
   • Avoid supraphysiologic levels

By following these steps, you can safely initiate testosterone replacement therapy while minimizing risks and optimizing benefits for patients with confirmed hypogonadism.