What is the recommended approach for testosterone testing and replacement therapy in individuals with suspected hypogonadism?

Recommended Approach for Testosterone Testing and Replacement Therapy in Suspected Hypogonadism

Testosterone testing should include morning total testosterone measurements on at least two separate occasions between 8-10 AM, along with free testosterone by equilibrium dialysis in patients with obesity or when total testosterone is borderline low, followed by additional diagnostic workup to determine the cause of hypogonadism before initiating replacement therapy. 1

Diagnostic Testing Algorithm

Initial Evaluation

• Assess for symptoms and signs of hypogonadism including decreased energy, libido, muscle mass, body hair, as well as hot flashes, gynecomastia, and infertility 1
• Measure morning total testosterone concentration between 8 AM and 10 AM 1
• If total testosterone is low, repeat the measurement on a separate morning to confirm 1, 2

Additional Testing

• In men with obesity or when total testosterone levels are near the lower limit of normal, measure:
  • Free testosterone by equilibrium dialysis (preferred method) 1
  • Sex hormone-binding globulin (SHBG) levels 1
• If testosterone levels are confirmed low, measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish between:
  • Primary hypogonadism (testicular failure): elevated LH/FSH 1, 3
  • Secondary hypogonadism (pituitary-hypothalamic dysfunction): low or normal LH/FSH 1, 2

Further Evaluation for Secondary Hypogonadism

• Measure serum prolactin and iron saturation 1
• Consider pituitary function testing 1
• Consider magnetic resonance imaging of the sella turcica 1

Testosterone Replacement Therapy

Indications for Treatment

• Symptomatic men with consistently low testosterone levels confirmed on at least two separate morning measurements 1, 2
• FDA-approved indications include primary hypogonadism and hypogonadotropic hypogonadism 4

Contraindications

• Breast or prostate cancer 2
• Palpable prostate nodule or induration 2
• PSA >4 ng/mL (or >3 ng/mL in high-risk men) without urological evaluation 2
• Hematocrit >50% 2
• Untreated severe obstructive sleep apnea 2
• Severe lower urinary tract symptoms 2
• Uncontrolled heart failure 2
• Recent myocardial infarction or stroke (within 6 months) 2
• Planning fertility in the near term 2

Treatment Options

• Transdermal preparations (gel, patch):

  • Provide stable day-to-day testosterone levels 1
  • Recommended as first-line for most patients due to convenience 1
  • Considerations: skin irritation with patches, risk of transfer with gels, higher cost 1

• Intramuscular injections:

  • Dosage: 50-400 mg every 2-4 weeks for hypogonadal males 4
  • Advantages: less frequent administration, lower cost 1
  • Disadvantages: fluctuating testosterone levels, injection discomfort 1

• Implantable testosterone pellets:

  • Advantage: long-term option requiring less frequent administration 1
  • Disadvantage: requires procedure for implantation 1

Monitoring

• Assess symptoms, adverse effects, and compliance 2
• Measure testosterone levels 2-3 months after starting treatment and after any dose change 1
  • For injections: measure midway between injections, targeting 500-600 ng/dL 1
  • For transdermal preparations: can measure at any time (peak values 6-8 hours after patch application) 1
• Once stable, monitor every 6-12 months 1
• Monitor hematocrit and PSA at baseline and annually in men ≥40 years 5

Benefits and Risks

Potential Benefits

• Improved sexual function and libido 1, 2
• Enhanced sense of well-being 3, 2
• Increased lean body mass and decreased body fat 1, 3
• Improved bone mineral density 3, 2
• Potential improvements in metabolic parameters (glucose control, insulin sensitivity) 1

Potential Risks

• Possible increased risk of cardiovascular events, though recent evidence suggests no increased risk of MI or stroke even in high-risk patients 5
• Polycythemia (elevated hematocrit) 3, 2
• Potential stimulation of prostate growth 3
• Sleep apnea exacerbation 2

Common Pitfalls to Avoid

• Initiating therapy without confirming low testosterone with repeated morning measurements 1, 2
• Failing to measure free testosterone in obese patients or those with borderline low total testosterone 1
• Not completing appropriate diagnostic workup to determine the cause of hypogonadism 1
• Inadequate monitoring of testosterone levels, hematocrit, and PSA during treatment 1, 2
• Starting therapy in men with contraindications 2