When to consider testosterone replacement therapy (TRT) in patients with hypogonadism?

When to Consider Testosterone Replacement Therapy (TRT) for Hypogonadism

Testosterone replacement therapy should be initiated in men with confirmed low testosterone levels (<300 ng/dL) on at least two separate morning measurements, along with symptoms such as decreased libido, fatigue, and mood changes. 1, 2, 3

Diagnostic Criteria for Hypogonadism

• Morning total testosterone concentration should be drawn between 8 AM and 10 AM, with levels below 300 ng/dL considered low 3
• Confirmation requires at least two separate measurements showing low testosterone 2, 3
• Free testosterone level by equilibrium dialysis and sex hormone-binding globulin level should be measured, especially in men with obesity 3
• If testosterone levels are subnormal, serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) should be measured to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 3

Symptoms Indicating Need for TRT

• Decreased libido and erectile dysfunction 1, 3
• Decreased energy, fatigue, and reduced vitality 1, 3
• Decreased strength and endurance 1
• Deterioration in work performance 1
• Depressive symptoms 1
• Loss of muscle mass 3

FDA-Approved Indications for TRT

• Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy 4
• Hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation 4

Treatment Considerations

When to Start TRT

• For men with frankly low free testosterone levels on at least two separate assessments 1
• After completing a hypogonadism workup to rule out etiologies unrelated to age or obesity 1
• When symptoms are bothersome enough to impact quality of life 1

Treatment Options

• Transdermal preparations (gel, patch) provide more stable day-to-day testosterone levels 1, 3
• Intramuscular injections are more economical ($156.24 annually vs $2,135.32 for transdermal) 1, 3
• For intramuscular injections, 50 to 400 mg should be administered every two to four weeks 4
• Patient preferences should be considered - some prefer injections due to lower cost, while others prefer gels for convenience and ease of use 1

Monitoring During TRT

• Testosterone levels should be tested 2-3 months after treatment initiation and/or after any dose change 3
• For patients receiving testosterone injections, levels should be measured midway between injections, targeting mid-normal values (500-600 ng/dL) 3
• Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 3
• Monitor for potential side effects including erythrocytosis, which occurs more frequently with injections than with transdermal preparations 3
• Monitor prostate-specific antigen (PSA) and prostate function, especially in men over 40 years old 2

Expected Benefits of TRT

• Improved sexual function and libido 1, 3
• Increased lean body mass and decreased abdominal subcutaneous adipose tissue 1
• Potential improvements in fasting plasma glucose, insulin resistance, triglyceride levels, and HDL cholesterol 3
• Improvements in vitality and fatigue, though effect sizes may be small 1
• Possible improvements in depressive symptoms 1

Contraindications and Cautions

• TRT should not be used in eugonadal individuals 5
• TRT may compromise fertility by suppressing the hypothalamic-pituitary-gonadal axis 3
• Use with caution in men with recent cardiovascular disease 1
• Long-term safety data is limited, particularly for men aged 18 to 50 years 3

Common Pitfalls to Avoid

• Treating based on symptoms alone without laboratory confirmation of low testosterone levels 5
• Failing to distinguish between primary and secondary hypogonadism 5
• Not considering the impact of obesity on testosterone levels - men with obesity may have low total testosterone due solely to low sex hormone-binding globulin but normal free testosterone levels 1
• Not measuring morning testosterone levels, which can lead to false diagnoses due to diurnal variation 3
• Overlooking potential causes of secondary hypogonadism such as medications (e.g., opioids) 2