What is the treatment for a male with hypogonadism (low testosterone)?

Treatment of Male Hypogonadism (Low Testosterone)

For men with symptomatic low testosterone, testosterone replacement therapy (TRT) is recommended, with intramuscular formulations preferred due to lower cost and similar effectiveness compared to transdermal options. 1, 2

Diagnosis Criteria

• Diagnosis requires both low testosterone levels (<300 ng/dL) on at least two separate morning measurements AND presence of symptoms/signs 1
• Symptoms may include:
  • Sexual dysfunction (reduced libido, erectile dysfunction) 1
  • Reduced energy, fatigue, diminished work performance 1
  • Depression, reduced motivation, poor concentration 1
  • Infertility 1
• Additional testing should include:
  • Luteinizing hormone (LH) levels to determine if hypogonadism is primary or secondary 1
  • Prolactin in patients with low testosterone and low/normal LH levels 1
  • Estradiol in patients with breast symptoms or gynecomastia before starting TRT 1

Treatment Algorithm

Step 1: Confirm Diagnosis and Type of Hypogonadism

• Primary hypogonadism: testicular failure due to cryptorchidism, bilateral torsion, orchitis, or orchidectomy 3, 4
• Hypogonadotropic hypogonadism: gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury 3, 4

Step 2: Select Appropriate Treatment Based on Symptoms

• For sexual dysfunction: TRT is recommended to improve sexual function 5, 2
• For energy, vitality, physical function, or cognition alone: TRT is not recommended 5

Step 3: Choose Formulation

• Intramuscular injections are recommended as first-line due to:
  • Significantly lower cost ($156.24 annually vs. $2,135.32 for transdermal) 1, 2
  • Similar clinical effectiveness and adverse event profile to transdermal formulations 5, 2
• Available options include:
  • Testosterone enanthate (IM) 3
  • Testosterone cypionate (IM) 4
  • Topical gel/cream (more convenient but more expensive) 2, 6

Expected Benefits

• Small improvement in global sexual function (moderate-certainty evidence) 2
• Small improvement in erectile function (low-certainty evidence) 2
• Modest improvements in vitality and fatigue 2
• Slight improvement in depressive symptoms 2
• Increased muscle mass, strength, and bone mineral density 1, 7

Monitoring and Follow-up

• Check testosterone levels 2-3 months after starting treatment 1
• Re-evaluate symptoms within 12 months and periodically thereafter 5, 1
• Discontinue treatment if no improvement in sexual function occurs 5
• Monitor for adverse effects, particularly erythrocytosis (occurs in 3-18% with transdermal and up to 44% with injections) 1

Contraindications and Precautions

• Absolute contraindications:
  • Active or treated male breast cancer 1
  • Men seeking fertility (standard TRT) 1, 8
• Relative contraindications/precautions:
  • Recent cardiovascular disease 1
  • Untreated sleep apnea or severe heart failure 7
  • Hyperviscosity risk 7

Alternative Treatments

• For men with secondary hypogonadism who wish to preserve fertility:
  • Selective estrogen receptor modulators (SERMs) 1, 8
  • Gonadotropin therapy 1, 8
• For obese men:
  • Weight loss through low-calorie diets and physical activity can improve testosterone levels 1

Important Clinical Pitfalls

• TRT suppresses the hypothalamic-pituitary-gonadal axis through negative feedback, which can impair fertility 8
• FDA approval for testosterone products specifically covers primary hypogonadism and hypogonadotropic hypogonadism, not age-related hypogonadism 3, 4
• Treating based on symptoms alone without laboratory confirmation of low testosterone is not recommended 9
• Failing to distinguish between primary and secondary hypogonadism can lead to inappropriate treatment 9