Is transdermal testosterone therapy safe in patients with a history of alcohol (ethanol) abuse?

Safety of Transdermal Testosterone Therapy in Alcoholics

Transdermal testosterone therapy should be used with caution in patients with a history of alcohol abuse due to theoretical risks of hepatocellular carcinoma, but can be administered after careful discussion of these risks. 1

Testosterone and Alcoholism: Physiological Considerations

Alcoholism affects testosterone levels in complex ways:

• Alcohol has a direct toxic effect on testosterone synthesis, resulting in decreased levels during active drinking 2
• Sex hormone-binding globulin (SHBG) is often elevated in alcoholics, affecting free testosterone measurements 1
• After withdrawal and maintaining sobriety (approximately 6 weeks), testosterone levels may actually increase above normal control levels 3

Safety Assessment Algorithm

1. Evaluate liver function

   • Comprehensive liver function tests must be performed before initiating therapy
   • Transdermal testosterone is preferred over oral formulations which have higher risk of liver toxicity 1

2. Assess current drinking status

   • Active drinking: Consider delaying therapy until patient achieves sobriety
   • Recovered alcoholic: Monitor more frequently for adverse effects

3. Monitor for specific complications

   • Erythrocytosis: Higher risk in alcoholics with underlying liver or pulmonary disease

     • Transdermal preparations have lower risk (2.8-5.5%) compared to injections (43.8%) 1
     • Monitor hematocrit/hemoglobin regularly, especially during first 3 months 4

   • Fluid retention: Use caution in patients with congestive heart failure 4

   • Liver effects: Despite theoretical concerns, long-term oral testosterone did not worsen liver morphology in men with alcoholic cirrhosis in a controlled study 5

Dosing and Monitoring Recommendations

• Target testosterone levels: 450-600 ng/dL (mid-normal range) 4
• Initial monitoring: Check testosterone levels 2-3 months after initiation 4
• Timing of levels: Measure at both peak (+2h after application) and trough (+23h) for optimal dosing 6
• Dose adjustment based on morning testosterone levels:

  • 750 ng/dL: Decrease daily dose

  • 350-750 ng/dL: No change
  • <350 ng/dL: Increase daily dose 4

Important Caveats

• Free testosterone is a better index of gonadal status than total testosterone in alcoholics due to altered SHBG levels 1
• Calculate free testosterone index (ratio of total testosterone/SHBG) to assess hypogonadism; a ratio <0.3 indicates hypogonadism 1
• Morning testosterone measurements are essential due to significant diurnal variation 1
• Patients should be informed about the importance of maintaining sobriety during therapy to minimize adverse effects

Conclusion

While transdermal testosterone can be used in patients with a history of alcoholism, careful monitoring is required. The evidence suggests that transdermal formulations are safer than oral or injectable testosterone in this population due to lower risk of erythrocytosis and minimal liver effects. The decision to initiate therapy should consider the patient's current drinking status, liver function, and ability to comply with monitoring requirements.