What percentage of men have hypogonadism (low testosterone levels) and may benefit from testosterone replacement therapy?

Prevalence of Hypogonadism and Benefits of Testosterone Replacement Therapy

Approximately 2 to 4 million men in the United States have hypogonadism (low testosterone levels) that may benefit from testosterone replacement therapy, though only about 5% of affected men currently receive treatment. 1

Epidemiology and Prevalence

Hypogonadism is characterized by low serum testosterone levels occurring with specific symptoms including:

• Diminished libido and sense of vitality
• Erectile dysfunction
• Reduced muscle mass and bone density
• Depression and fatigue
• Anemia
• Impaired cognition

The prevalence of hypogonadism increases with age, with older men often experiencing what is termed "andropause" or "androgen deficiency of the aging male." 1

Benefits of Testosterone Replacement Therapy

Testosterone replacement therapy (TRT) has demonstrated several benefits for men with confirmed hypogonadism:

1. Sexual function improvements: TRT provides small but significant improvements in sexual functioning in men with low testosterone levels (low to moderate-certainty evidence) 1

2. Quality of life improvements: Small but meaningful improvements in quality of life metrics have been documented (low to moderate-certainty evidence) 1

3. Other potential benefits:

   • Improved bone density
   • Increased muscle mass
   • Better body composition
   • Enhanced mood
   • Improved erythropoiesis 1

Limitations of Current Evidence

Several important limitations exist in the current evidence base:

• Few trials exceed 1 year in duration 1
• Randomized controlled trials are not powered to assess important harms 1
• Limited data available for men aged 18-50 years 1
• Definitions of "low testosterone" vary considerably across studies 1
• Long-term efficacy and safety remain uncertain 1

Potential Risks and Monitoring Requirements

Testosterone therapy carries several potential risks that require monitoring:

• Cardiovascular effects: Current evidence suggests neutral or possibly beneficial effects on cardiovascular risk 1
• Erythrocytosis: Risk varies by administration route (3-18% with transdermal, up to 44% with injection) 1
• Prostate effects: Prostate volume increases during TRT, though urinary symptoms typically don't worsen significantly 1
• Prostate cancer risk: Remains controversial with unknown level of risk requiring long-term monitoring 1
• Other potential side effects: Fluid retention, sleep apnea, gynecomastia, skin reactions, and testicular atrophy 1

Patient Preferences

When considering treatment options:

• 53% of patients receiving testosterone treatment prefer injectable testosterone over gel-based or pellet regimens, primarily due to lower cost 1
• Among patients who have used TRT products for more than a month, 71% preferred topical gel over injections or patches, citing convenience and ease of use 1
• The most bothersome symptoms prompting men to seek treatment are erectile dysfunction (66%), decreased sex drive (56%), and loss of energy/increased tiredness (47-59%) 1

Cost Considerations

The annual cost per beneficiary for TRT varies significantly by formulation:

• Transdermal: $2,135.32 (2016 Medicare Part D data)
• Intramuscular: $156.24 (2016 Medicare Part D data) 1

Clinical Algorithm for TRT Decision-Making

1. Confirm diagnosis of hypogonadism:

   • Document low morning testosterone levels on at least two occasions
   • Verify presence of clinical symptoms (sexual dysfunction, fatigue, reduced muscle mass)

2. Assess for contraindications:

   • Prostate cancer or high risk of prostate cancer
   • Severe cardiovascular disease
   • Polycythemia
   • Thrombophilia
   • Desire for fertility in the near future 2

3. Consider patient-specific factors:

   • Age (benefits more established in older men with symptoms)
   • Symptom severity (sexual dysfunction most responsive)
   • Cost considerations (injectable forms more affordable)
   • Comorbidities (obesity, diabetes may influence response)

4. Implement appropriate monitoring:

   • Baseline PSA and digital rectal examination
   • Hematocrit/hemoglobin
   • Lipid profile
   • Regular follow-up for symptom assessment

Conclusion

While a substantial number of men have hypogonadism that could potentially benefit from testosterone replacement therapy, the decision to treat should be based on confirmed low testosterone levels with associated symptoms, careful consideration of potential risks, and ongoing monitoring. The most recent evidence suggests benefits primarily for sexual function and quality of life, with uncertain long-term safety profiles.