What is the treatment for hypogonadism (low testosterone)?

Treatment for Hypogonadism (Low Testosterone)

Testosterone replacement therapy (TRT) is the first-line treatment for confirmed hypogonadism in adult males with symptoms and biochemically low testosterone levels. 1

Diagnosis Confirmation

• Diagnosis requires both persistent specific symptoms and confirmed testosterone deficiency through biochemical testing 1
• Morning serum total testosterone measurements should be repeated on at least two separate days to confirm low levels 2, 1
• Free or bioavailable testosterone levels should also be measured in men with total testosterone levels close to the lower limit 2
• Further testing (LH and FSH levels) is needed to distinguish between primary (testicular) and secondary (pituitary-hypothalamic) hypogonadism 2, 1

Indications for Treatment

• Primary hypogonadism: testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage 3
• Hypogonadotropic hypogonadism: gonadotropin or LHRH deficiency or pituitary-hypothalamic injury 3
• Common symptoms warranting treatment include:
  • Decreased sexual desire (libido) or activity 2
  • Erectile dysfunction 1
  • Decreased sense of vitality 1
  • Loss of muscle mass and strength 1

Treatment Options

1. Testosterone Replacement Therapy (First-line)

Intramuscular Injections

• Testosterone cypionate or enanthate administered every 2-3 weeks 1, 4
• Peak serum levels occur 2-5 days after injection, with return to baseline usually observed 10-14 days after injection 1
• Most economical option 1, 4
• Higher risk of erythrocytosis compared to topical preparations 1

Transdermal Preparations

• Gels or patches provide more stable day-to-day testosterone levels 1
• Often preferred for initial treatment due to stability of testosterone levels 1
• Apply to clean, dry, intact skin of the upper arms and shoulders 3
• Avoid application to abdomen, genitals, chest, armpits, or knees 3

2. Alternative Treatments (For Special Situations)

Gonadotropin Therapy

• Option for men wishing to preserve fertility 5, 6
• Combination of human chorionic gonadotropin (hCG) and FSH promotes testicular growth and spermatogenesis 6
• Success rates for spermatogenesis approximately 80% with combination therapy 6

Selective Estrogen Receptor Modulators (SERMs)

• Clomiphene citrate and tamoxifen may be options for functional central hypogonadism 5
• Off-label use with limited data on efficacy for hypogonadal symptoms 5

Monitoring and Dose Adjustment

• Testosterone levels should be tested 2-3 months after treatment initiation and after any dose change 1
• For patients on testosterone injections, levels should be measured midway between injections, targeting a mid-normal value (500-600 ng/dL) 1
• Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 1
• Dose adjustment based on pre-dose morning serum testosterone concentration 3

Potential Benefits of Treatment

• Improved sexual function and libido 1
• Enhanced sense of well-being 4
• Increased lean body mass and decreased body fat 4
• Improved bone mineral density 4
• Potential improvements in fasting plasma glucose, insulin resistance, and lipid profile 1

Potential Risks and Contraindications

Contraindications

• Prostate or breast cancer 7, 4
• Untreated severe obstructive sleep apnea 8
• Severe heart failure 7
• Erythrocytosis 7
• Hyperviscosity 8

Side Effects and Monitoring

• Erythrocytosis (elevated hematocrit) - monitor hematocrit regularly 1, 7
• Fluid retention 7
• Potential worsening of benign prostatic hyperplasia 1
• Gynecomastia 7
• Risk of venous thromboembolic events 7
• Potential cardiovascular risks - some studies report increased risk of major adverse cardiovascular events 7

Important Monitoring Parameters

• Hematocrit for detection of polycythemia 4
• Digital rectal examination with PSA measurement for prostate cancer screening 4
• Bone mineral density in selected men 4

Treatment Duration and Follow-up

• Re-evaluate patients 3 months after testosterone initiation and at least annually thereafter 8
• If no improvement in sexual function after 12 months, consider discontinuing treatment 1

Common Pitfalls

• Treating "age-related hypogonadism" without confirmed symptoms and low testosterone levels 3
• Failure to distinguish between primary and secondary hypogonadism 1
• Inadequate monitoring for side effects, particularly erythrocytosis and prostate issues 4
• Not considering fertility preservation in younger men 5