What are the indications and effects of testosterone replacement therapy in elderly men with symptomatic hypogonadism?

Testosterone Replacement Therapy in Elderly Men with Symptomatic Hypogonadism

Testosterone replacement therapy (TRT) should only be initiated in elderly men with confirmed symptomatic hypogonadism, primarily to improve sexual function, and should not be used for improving energy, vitality, physical function, or cognition. 1

Diagnosis of Hypogonadism in Elderly Men

• Hypogonadism should be diagnosed based on both persistent specific symptoms and confirmed low testosterone levels 2
• Morning total testosterone concentration should be drawn between 8-10 AM and repeated if low 2
• Free testosterone by equilibrium dialysis and sex hormone-binding globulin levels should be measured, especially in men with obesity 2
• Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) should be measured to distinguish primary from secondary hypogonadism 2
• Low testosterone in elderly men is defined as total testosterone <275 ng/dL (9.54 nmol/L) with associated symptoms 1

Indications for Testosterone Therapy

• FDA-approved indications include primary hypogonadism (testicular failure) and hypogonadotropic hypogonadism 3
• TRT should be considered primarily for improving sexual function in elderly men with symptomatic hypogonadism 1
• Symptoms warranting consideration of TRT include:
  • Sexual dysfunction (decreased libido, erectile dysfunction) 1, 2
  • Reduced sense of vitality 2
  • Decreased muscle mass and bone density 1
  • Depression 1
  • Anemia 1

Benefits of Testosterone Therapy in Elderly Men

• Small but significant improvements in sexual function and quality of life 1
• Potential improvement in bone mineral density 1, 4
• Modest improvements in body composition (increased muscle mass, decreased fat mass) 4
• Possible improvement in insulin resistance in selected patients 2, 4
• May help correct mild anemia 1

Limited or No Benefits

• Little to no effect on physical functioning 1
• Little to no improvement in depressive symptoms 1
• No significant improvement in energy or vitality 1
• No proven benefit for cognitive function 1, 2, 4

Potential Risks and Monitoring

• Erythrocytosis (elevated hematocrit) - more common with injectable forms 1
• Fluid retention 1
• Potential worsening of benign prostatic hyperplasia 1
• Theoretical risk of prostate cancer stimulation, though unproven 1
• Sleep apnea exacerbation 1
• Gynecomastia 1
• Testicular atrophy and infertility 1
• Skin reactions (acne, oiliness) 1
• Uncertain cardiovascular risk profile 4, 5

Monitoring Recommendations

• Testosterone levels should be tested 2-3 months after treatment initiation and after any dose change 2
• For injectable testosterone, levels should be measured midway between injections 2
• Once stable, monitoring every 6-12 months is typically sufficient 2
• Monitor hematocrit, prostate-specific antigen (PSA), and clinical response 2, 4
• Consider bone density assessment 2, 4

Treatment Formulations

• Intramuscular testosterone injections (cypionate or enanthate) administered every 2-3 weeks 2

  • Peak levels occur 2-5 days after injection with return to baseline in 10-14 days 1
  • Higher risk of erythrocytosis compared to topical preparations 1
  • More cost-effective than transdermal formulations 1

• Transdermal testosterone (gels, patches)

  • Provide more stable day-to-day testosterone levels 2
  • May be preferred for initial treatment in elderly men 2, 4
  • Lower risk of erythrocytosis 1

Treatment Algorithm

1. Confirm diagnosis with repeated morning testosterone measurements and presence of symptoms 2

2. Rule out contraindications:

   • Active prostate or breast cancer 4
   • Recent cardiovascular events (MI, stroke within 4 months) 4
   • Severe heart failure 4
   • Desire for fertility 4

3. Initiate treatment:

   • Consider starting with transdermal preparations in elderly men 2, 4
   • If cost is a concern, intramuscular injections are more economical 1
   • Target mid-normal testosterone levels (500-600 ng/dL) 2

4. Evaluate response at 3 months:

   • Assess improvement in sexual symptoms 1
   • Measure testosterone levels 2
   • Check hematocrit and PSA 2

5. If no improvement in sexual function after 12 months, discontinue treatment 1

Important Caveats

• TRT should not be initiated to improve energy, vitality, physical function, or cognition 1
• Long-term safety data in elderly men remains limited 1, 5
• Benefits and risks should be clearly discussed with patients 6
• Consider weight loss as first-line intervention in obese men with low testosterone 4