What are the indications for Testosterone Replacement Therapy (TRT)?

Indications for Testosterone Replacement Therapy (TRT)

Testosterone replacement therapy is indicated for men with documented hypogonadism, characterized by low serum testosterone levels (below 300 ng/dL on at least two separate morning measurements) combined with specific signs and symptoms of testosterone deficiency. 1

Primary Indications

Confirmed Hypogonadism with Symptoms

• Primary hypogonadism (congenital or acquired) - testicular failure due to:

  • Cryptorchidism
  • Bilateral torsion
  • Orchitis
  • Vanishing testis syndrome
  • Orchidectomy 2, 3, 4

• Hypogonadotropic hypogonadism (congenital or acquired):

  • Idiopathic gonadotropin or LHRH deficiency
  • Pituitary-hypothalamic injury from tumors, trauma, or radiation 2, 3, 4

Diagnostic Requirements

1. Laboratory confirmation: Total testosterone levels below 300 ng/dL measured in the morning on at least two separate occasions 1
2. Presence of symptoms associated with testosterone deficiency:

Sexual Symptoms

• Reduced libido
• Erectile dysfunction
• Decreased spontaneous/morning erections 1

Physical Symptoms

• Decreased energy and physical strength
• Fatigue
• Diminished muscle mass
• Reduced bone density
• Anemia 5, 1

Psychological Symptoms

• Depressed mood
• Decreased motivation
• Concentration difficulties 1

Contraindications for TRT

Absolute Contraindications

• Active prostate or breast cancer 1, 3, 4
• Desire for fertility in the near term 1
• Severe untreated sleep apnea (though recent evidence suggests this may be reconsidered) 5, 1
• Uncontrolled heart failure 1
• Recent cardiovascular events 1

Relative Contraindications

• History of hepatocellular carcinoma 1
• History of thrombosis 1
• Significant cardiovascular risk factors 1

Special Considerations

Fertility Concerns

• TRT suppresses spermatogenesis and can cause oligospermia or azoospermia 1
• For men desiring fertility, alternative treatments should be considered:
  • Human chorionic gonadotropin (hCG)
  • Selective estrogen receptor modulators (SERMs)
  • Aromatase inhibitors 1

Metabolic Conditions

• Men with obesity, metabolic syndrome, or diabetes may benefit from TRT, which can improve insulin sensitivity 5
• However, lifestyle modifications (weight loss, exercise) should be first-line for metabolic benefits and can sometimes reverse obesity-associated secondary hypogonadism 5, 1

Prostate Concerns

• Current evidence suggests TRT does not increase prostate cancer risk 5
• TRT is generally safe in men with lower urinary tract symptoms (LUTS) except in those with severe symptoms 5

Monitoring Requirements

Once TRT is initiated, patients should be monitored for:

• Testosterone levels (target: mid-normal range 450-600 ng/dL)
• Hemoglobin/hematocrit (discontinue if Hct >54%)
• PSA levels
• Symptoms improvement (consider discontinuation after 3-6 months if no improvement) 1

Important Caveats

• TRT should not be used in eugonadal men 5
• TRT is not recommended solely for weight reduction or to enhance cardiometabolic status 5
• TRT is not recommended to improve cognition, vitality, or physical strength in aging men without documented hypogonadism 5
• "Age-related hypogonadism" alone is not an FDA-approved indication for TRT 3, 4

TRT can significantly improve quality of life in truly hypogonadal men, particularly regarding sexual function, energy levels, and mood, but must be prescribed appropriately with careful consideration of both benefits and potential risks.