What is the approach to diagnosing and treating male hypogonadism?

Diagnosis and Treatment of Male Hypogonadism

The diagnosis of male hypogonadism requires both clinical symptoms consistent with testosterone deficiency and unequivocally low morning testosterone levels measured on at least two separate occasions. 1, 2, 3

Diagnostic Approach

Initial Evaluation

• Clinical symptoms suggesting hypogonadism:
  • Decreased sexual desire (libido) or activity
  • Erectile dysfunction
  • Decreased energy and well-being
  • Reduced muscle mass and strength
  • Decreased body and facial hair
  • Hot flashes
  • Gynecomastia 1, 2

Laboratory Testing

1. Morning total testosterone level (drawn between 8-10 AM) is the initial test 2, 4

   • Normal range: 300-800 ng/dL
   • Total testosterone <150 ng/dL: Highly specific for hypogonadism 5
   • Total testosterone <200 ng/dL: Clear indication of hypogonadism 6
   • Total testosterone 200-350 ng/dL: Requires additional testing 5, 6

2. Confirmatory testing:

   • Repeat morning total testosterone measurement on a different day 4, 3
   • For borderline results or suspected SHBG abnormalities: Measure free testosterone 1, 2
   • Free testosterone should be measured by equilibrium dialysis or calculated using accurate formulas that include total testosterone, SHBG, and albumin 1, 3

3. Further evaluation to determine etiology:

   • Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) 1, 2, 7
     • High LH/FSH: Primary hypogonadism (testicular failure)
     • Low/normal LH/FSH: Secondary hypogonadism (pituitary/hypothalamic disorder)
   • Measure prolactin if testosterone is low with low/normal LH 1
   • Consider pituitary MRI if total testosterone <150 ng/dL with low/normal LH 1
   • Measure estradiol in men with breast symptoms/gynecomastia 1

Treatment Approach

Testosterone Replacement Therapy (TRT)

• Indications: Symptomatic men with confirmed low testosterone levels 1, 3
• Benefits: Improved sexual function, increased well-being, increased lean body mass, decreased body fat, improved bone mineral density 1, 2

Formulations

1. Transdermal preparations (gels, patches):

   • Starting dose for 1.62% gel: 40.5 mg (2 pump actuations) applied once daily to shoulders and upper arms 4
   • Advantages: More stable day-to-day testosterone levels 2
   • Dose adjustment: Based on morning testosterone levels at 14 and 28 days 4

2. Injectable testosterone:

   • Testosterone cypionate or enanthate: Weekly to biweekly injections 7
   • Testosterone undecanoate: Quarterly injections 7

3. Implantable pellets: Longer-term treatment option 2

Monitoring

• Assess symptoms and serum testosterone levels to confirm adequate replacement 7
• Monitor hematocrit for polycythemia 4, 7
• Prostate cancer screening: Digital rectal exam and PSA 4, 7
• Monitor for cardiovascular risk factors 1

Special Considerations

• Fertility preservation: Standard TRT suppresses spermatogenesis 8

  • Alternative options for men desiring fertility:
    • Nasal testosterone preparations
    • Clomiphene citrate
    • Exogenous gonadotropins 8

• Contraindications to TRT 4, 3:

  • Breast or prostate cancer
  • Elevated PSA (>4 ng/mL)
  • Severe untreated sleep apnea
  • Severe lower urinary tract symptoms
  • Recent myocardial infarction or stroke (within 6 months)
  • Uncontrolled heart failure
  • Thrombophilia
  • Planning fertility in the near term

Pitfalls and Caveats

• Obesity is a major confounder in testosterone assessment 1, 2
• Morning testing is essential as testosterone levels fluctuate throughout the day 2
• Total testosterone between 280-350 ng/dL is not sensitive enough to reliably exclude hypogonadism 5
• Testosterone therapy in older men has been associated with increased coronary artery plaque volume in some studies 1, 2