What are the criteria for starting testosterone replacement therapy in patients with hypogonadism?

Criteria for Starting Testosterone Replacement Therapy in Hypogonadism

Testosterone replacement therapy should be initiated when a patient has at least two morning testosterone measurements confirming low levels (total testosterone <300 ng/dL and/or free testosterone below normal range) AND clinical symptoms of hypogonadism, with a completed workup to determine the underlying cause. 1, 2, 3

Diagnostic Criteria

Laboratory Assessment

• Morning testosterone measurements:
  • At least two separate morning (between 8-10 AM) total testosterone measurements below normal range (<300 ng/dL) 1, 2, 3
  • Free testosterone by equilibrium dialysis should be measured, especially in obese patients 1
  • Sex hormone-binding globulin (SHBG) levels should be measured in obese patients 1

Etiological Workup

• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish:

  • Primary hypogonadism (testicular failure): elevated LH/FSH
  • Secondary hypogonadism (pituitary/hypothalamic dysfunction): low or normal LH/FSH 1, 3

• For secondary hypogonadism, additional testing:

  • Serum prolactin
  • Iron saturation
  • Pituitary function tests
  • MRI of sella turcica if indicated 1

Clinical Symptoms and Signs

• Decreased libido
• Erectile dysfunction
• Reduced energy levels
• Decreased muscle mass
• Increased body fat (especially abdominal)
• Loss of body hair
• Hot flashes
• Gynecomastia
• Infertility
• Depression/mood changes 1, 2

FDA-Approved Indications

• Primary hypogonadism (congenital or acquired)
• Hypogonadotropic hypogonadism (congenital or acquired) 3, 4

Important Considerations Before Starting Therapy

Contraindications

• Prostate cancer or male breast cancer
• Desire for fertility in the near future
• Pregnancy (in women who might be exposed)
• Hypersensitivity to testosterone products 3, 4

Relative Contraindications

• Severe obstructive sleep apnea
• Severe lower urinary tract symptoms
• Uncontrolled congestive heart failure
• Hematocrit >54%
• Uncontrolled hypertension 2

Pre-Treatment Evaluation

• Baseline hematocrit
• PSA (in men ≥40 years)
• Liver function tests
• Lipid profile
• Blood pressure assessment
• Cardiovascular risk assessment 2

Treatment Approach

1. Confirm diagnosis with two morning testosterone measurements and presence of symptoms
2. Determine underlying cause through LH/FSH and additional testing
3. Rule out contraindications and assess baseline parameters
4. Select appropriate testosterone formulation based on patient preference, cost, and clinical factors
5. Start at recommended dose based on formulation:
   • Oral testosterone undecanoate: 200 mg twice daily with food 3
   • Topical gel 1.62%: 40.5 mg applied once daily to shoulders/upper arms 4
   • Intramuscular or other formulations as appropriate 2

Monitoring

• Check testosterone levels 2-3 months after starting therapy or dose adjustment
• Target mid-normal testosterone range (500-600 ng/dL)
• Monitor hematocrit, PSA, liver function, lipid profile every 6-12 months
• Evaluate for symptom improvement
• Monitor blood pressure regularly due to risk of hypertension 2, 3

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 1, 2, 3

Testosterone replacement therapy can significantly improve quality of life, sexual function, body composition, and metabolic parameters in appropriately diagnosed patients with hypogonadism. However, careful patient selection, proper diagnostic workup, and ongoing monitoring are essential to maximize benefits while minimizing risks.