What are the treatment options for symptomatic low testosterone?

Treatment Options for Symptomatic Low Testosterone

Testosterone replacement therapy (TRT) is the first-line treatment for men with symptomatic low testosterone, with formulation choice based on patient preference, cost considerations, and clinical factors. 1, 2

Diagnosis Confirmation

• 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
• Physical signs include changes in body habitus, reduced body hair, increased BMI/waist circumference, gynecomastia, and testicular abnormalities 1
• Measure luteinizing hormone (LH) levels to 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

1. Testosterone Replacement Therapy

Formulations:

• Topical gels/creams:

  • Preferred by 71% of patients for convenience and ease of use 2
  • Apply to clean, dry skin of upper arms and shoulders 3
  • More expensive ($2,135.32 annually) 1
  • Provides stable day-to-day testosterone levels 4
  • Risk of secondary exposure to women and children 3

• Intramuscular injections:

  • More economical option ($156.24 annually) 1, 2
  • Similar clinical effectiveness and adverse event profile to transdermal formulations 2
  • May cause fluctuating testosterone levels 4

Expected Benefits:

• Improved sexual function and erectile function 2
• Modest improvements in vitality, fatigue, and depressive symptoms 2
• Increased muscle mass, strength, and bone mineral density 2

Monitoring:

• Check testosterone levels 2-3 months after starting treatment 4
• Re-evaluate symptoms within 12 months and periodically thereafter 2, 4
• Monitor for adverse effects including erythrocytosis, which occurs in 3-18% with transdermal and up to 44% with injections 4

2. Alternative Treatments

• Selective estrogen receptor modulators (SERMs):

  • Clomiphene citrate or tamoxifen for men with secondary hypogonadism, especially those wishing to preserve fertility 1, 5
  • Off-label use with limited data on symptom improvement 5

• Gonadotropin therapy:

  • For secondary hypogonadism patients seeking fertility 1
  • Combination of human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) 1
  • Requires frequent injections 5

• Lifestyle modifications:

  • Weight loss through low-calorie diets can improve testosterone levels in obese men 1
  • Physical activity shows benefits correlating to exercise duration and weight loss 1
  • May yield modest testosterone increases (1-2 nmol/L) 1

Contraindications and Precautions

• Absolute contraindications:

  • Active or treated male breast cancer 1
  • Men seeking fertility (standard TRT) 1, 6
  • Untreated prostate cancer 7

• Relative contraindications/precautions:

  • Severe lower urinary tract symptoms (LUTS) 1
  • Recent cardiovascular disease 1
  • Polycythemia, peripheral edema, cardiac and hepatic dysfunction 7

Treatment Algorithm

1. Confirm diagnosis: Two morning testosterone levels <300 ng/dL plus symptoms 1
2. Determine type of hypogonadism: Measure LH/FSH levels 1
3. Assess for contraindications and fertility desires 1, 6
4. Select appropriate treatment:
   • If fertility desired: Consider gonadotropins or SERMs 1, 5
   • If no fertility concerns: Choose TRT formulation based on patient preference and cost 2
   • If obesity-related hypogonadism: Consider lifestyle modifications alongside treatment 1
5. Start with recommended dose:
   • Topical: 40.5 mg applied once daily to shoulders/upper arms 3
   • Adjust dose based on pre-dose morning testosterone levels at 14 and 28 days 3
6. Monitor response and adjust as needed:
   • Target testosterone level: 350-750 ng/dL 3
   • Discontinue if no symptom improvement after 12 months 2, 4

Common Pitfalls to Avoid

• Failing to confirm diagnosis with two separate morning testosterone measurements 1
• Not evaluating for secondary causes of hypogonadism 4
• Continuing treatment despite lack of symptom improvement 4
• Ignoring fertility concerns in younger patients 1
• Using screening questionnaires alone without laboratory confirmation 1
• Inadequate monitoring for adverse effects 4