What are the treatment options for hypogonadism (low testosterone)?

Treatment Options for Hypogonadism (Low Testosterone)

Testosterone replacement therapy (TRT) is the first-line treatment for men with symptomatic hypogonadism, with formulation choice based on patient preference, cost considerations, and clinical factors. 1

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 reduced energy, diminished work performance, fatigue, depression, reduced motivation, poor concentration, infertility, reduced sex drive, and erectile dysfunction 1
• Measuring luteinizing hormone (LH) levels helps determine if hypogonadism is primary or secondary 1
• Consider measuring prolactin in patients with low testosterone and low/normal LH levels 1
• Measure estradiol in patients with breast symptoms or gynecomastia before starting TRT 1

Treatment Options

FDA-Approved Indications for TRT

• Primary hypogonadism: testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage 2
• Hypogonadotropic hypogonadism: gonadotropin or LHRH deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation 2
• Important limitation: Safety and efficacy in men with "age-related hypogonadism" have not been established 2

Formulation Options

• Topical gel/cream: Preferred by 71% of patients for convenience and ease of use 3

  • Annual cost approximately $2,135.32 1
  • Apply to clean, dry, intact skin of upper arms and shoulders 2
  • Risk of secondary exposure to women and children 2

• Intramuscular injections: More economical option ($156.24 annually) 1

  • May cause fluctuating testosterone levels 1
  • Higher risk of erythrocytosis (up to 44% vs 3-18% with transdermal) 1

Expected Benefits of TRT

• Small improvement in global sexual function (moderate-certainty evidence) 3
• Small improvement in erectile function (low-certainty evidence) 3
• Modest improvements in vitality and fatigue (SMD 0.17 higher) 4, 3
• Slight improvement in depressive symptoms (SMD 0.19 lower) 4, 3
• Increased muscle mass, strength, and bone mineral density 1

Contraindications and Precautions

• Absolute contraindications: active or treated male breast cancer and men seeking fertility (standard TRT) 1
• Relative contraindications: recent cardiovascular disease 1
• Risk of hypercalcemia in patients with breast cancer and immobilized patients 5
• Risk of peliosis hepatis and hepatic neoplasms with prolonged high-dose use 5
• Risk of venous thromboembolic events including DVT and pulmonary embolism 5
• Potential for edema with or without congestive heart failure in patients with preexisting cardiac, renal, or hepatic disease 5

Alternative Treatments

• For men with secondary hypogonadism, especially those wishing to preserve fertility:
  • Selective estrogen receptor modulators (SERMs) 1
  • Gonadotropin therapy 1
• Lifestyle modifications, including weight loss through low-calorie diets and physical activity, to improve testosterone levels in obese men 1

Monitoring and Follow-up

• Check testosterone levels 2-3 months after starting treatment 1
• Re-evaluate symptoms within 12 months and periodically thereafter 1, 3
• Monitor for adverse effects, including erythrocytosis 1
• Consider discontinuing treatment if no improvement in sexual function occurs 3
• Titrate dose based on pre-dose morning serum testosterone concentration from blood draws at approximately 14 days and 28 days after starting treatment 2

Treatment Considerations for Women

• Free testosterone is a better indicator of gonadal status than total testosterone in women 6
• For premenopausal women with hypogonadism, estrogen replacement with progesterone should be considered as first-line therapy 6
• Transdermal hormone replacement therapy may be appropriate for premenopausal or postmenopausal women with hormonal deficiencies 6

Common Pitfalls to Avoid

• Treating based on symptoms alone without laboratory confirmation of low testosterone levels 6
• Failing to distinguish between primary and secondary hypogonadism, which require different management approaches 6
• Using testosterone therapy in eugonadal individuals 6
• Inadequate monitoring for adverse effects 1
• High discontinuation rates (approximately 50% after 3 months for topical TRT) suggest the need for better patient education and follow-up 7