Are there contraindications to testosterone therapy in patients with primary sclerosing cholangitis (PSC)?

Testosterone Therapy in Primary Sclerosing Cholangitis: Contraindications and Considerations

Testosterone therapy is contraindicated in patients with primary sclerosing cholangitis (PSC) due to the potential risk of hepatotoxicity and worsening of underlying liver disease. 1

Rationale for Contraindication

Liver Disease Considerations

• PSC is a chronic cholestatic liver disease characterized by progressive fibrostenotic strictures of the bile ducts that can lead to cirrhosis and liver failure 1
• The British Society of Gastroenterology guidelines emphasize that PSC has an unpredictable disease course with serious complications, requiring lifelong surveillance 1, 2
• Any medication with potential hepatotoxicity should be avoided in patients with pre-existing liver disease, particularly cholestatic conditions like PSC

Specific Concerns with Testosterone

1. Hepatotoxicity risk:

   • Testosterone preparations, particularly oral formulations and certain injectable forms, have been associated with liver injury
   • Patients with PSC already have compromised liver function and impaired bile flow
   • Additional hepatotoxic stress could accelerate disease progression

2. Cholestasis exacerbation:

   • Androgens can worsen cholestasis by interfering with bile salt transport mechanisms
   • PSC patients already suffer from cholestasis, and testosterone may compound this problem 1

3. Potential for malignancy:

   • PSC patients have an increased lifetime risk of cholangiocarcinoma (10-15%) 1
   • The effect of exogenous androgens on this risk is unknown but potentially concerning

Clinical Decision Algorithm

1. Assess severity of PSC:

   • Early disease with minimal liver dysfunction
   • Advanced disease with evidence of cirrhosis or portal hypertension
   • Presence of dominant strictures or history of cholangitis

2. Consider alternative treatments for hypogonadism:

   • Non-hormonal approaches for symptom management
   • Consultation with endocrinology for alternative approaches

3. If testosterone is absolutely necessary:

   • Refer to transplant center for expert opinion
   • Consider transdermal formulations (may have less hepatic impact)
   • Implement intensive monitoring protocol:
     • Monthly liver function tests for first 3 months
     • Quarterly monitoring thereafter
     • Immediate discontinuation if liver enzymes worsen

Special Considerations

Patients Awaiting Liver Transplantation

Testosterone therapy should be avoided in PSC patients awaiting liver transplantation, as it may complicate transplant candidacy and post-transplant management 1

PSC with Overlap Syndromes

In patients with PSC-autoimmune hepatitis overlap syndrome, testosterone is particularly contraindicated as these patients may have more aggressive liver disease and are often on immunosuppressive therapy 1

Monitoring Requirements

If testosterone therapy is deemed absolutely necessary despite the risks:

• Baseline and regular monitoring of liver function tests
• Regular imaging of the biliary tree
• Vigilance for signs of cholangitis or worsening cholestasis

Conclusion

Given the progressive nature of PSC, the unpredictable disease course, and the potential hepatotoxicity of testosterone, the use of testosterone therapy in PSC patients carries significant risks. Alternative approaches to managing hypogonadism should be explored, and if testosterone is deemed absolutely necessary, it should only be used under close specialist supervision with frequent monitoring of liver function.