Can isoniazide (Isoniazid) cause infertility?

Isoniazid and Infertility

Based on current evidence, isoniazid can potentially cause infertility, particularly in males, through mechanisms including testicular oxidative stress, DNA damage, and hormonal disruption.

Mechanisms of Isoniazid-Induced Reproductive Effects

Male Reproductive Effects

Isoniazid has been associated with several mechanisms that can impair male fertility:

1. CYP2E1 Induction in Testes

   • Significant induction of CYP2E1 in rat testes (28-fold increase in mRNA expression)
   • Increased p-nitrophenolhydroxylase activity (7-fold) 1
   • These changes generate reactive oxygen species that can damage testicular tissue

2. Hormonal Disruption

   • Decreased serum testosterone levels (1.62-fold reduction in animal studies) 1
   • Reduced sperm count (19% decrease) and fertility 1

3. DNA Fragmentation

   • Increased testicular DNA fragmentation 1, 2
   • Damage to spermatogenic epithelium 1

Female Reproductive Effects

Recent research has also identified potential effects on female fertility:

• Disruption of oocyte maturation and fertilization 3
• Compromised meiotic progression through disruption of spindle assembly and chromosome arrangement 3
• Increased reactive oxygen species (ROS) and activation of oxidative stress response pathways 3
• Mitochondrial dysfunction in oocytes 3

Clinical Implications

Risk Assessment

The risk of isoniazid-induced infertility appears to be related to:

• Duration of treatment
• Dosage
• Individual susceptibility factors
• Concomitant use of other antituberculous medications

Drug Interactions

Isoniazid is a potent inhibitor of several cytochrome P450 isozymes (CYP2C9, CYP2C19, and CYP2E1) 4, which may affect metabolism of other medications and potentially compound reproductive effects.

Management Considerations

For Male Patients

• Consider fertility preservation options before starting long-term isoniazid therapy, especially in men of reproductive age
• Monitor for signs of testicular dysfunction during treatment
• Discuss potential fertility implications before initiating therapy

For Female Patients

• Limited evidence suggests potential effects on oocyte quality and fertilization 3
• Recent human data suggests no significant effect on pregnancy risk when isoniazid is used with hormonal contraception in women with HIV 5

Monitoring Recommendations

• No specific fertility monitoring guidelines exist for isoniazid therapy
• Consider baseline hormonal assessment in patients concerned about fertility
• Semen analysis may be considered for men planning future fertility

Special Considerations

Tuberculosis and Fertility

It's important to note that untreated tuberculosis itself can cause infertility, particularly genital tuberculosis. One case report demonstrated improvement in semen quality after treatment with isoniazid, ethambutol, and rifampicin for mycobacterial seminal vesiculitis 6.

Combination Therapy Effects

When isoniazid is co-administered with other antituberculous drugs (ethambutol, rifampicin, pyrazinamide), more pronounced reproductive effects have been observed, including:

• Increased lipid peroxidation in testis and sperm
• Decreased testicular glutathione content
• Significant decrease in male fertility 2

Conclusion

The evidence suggests that isoniazid can potentially affect fertility, particularly in males, through oxidative stress mechanisms and hormonal disruption. While animal studies show clear effects, human data remains limited. Clinicians should consider discussing fertility implications with patients of reproductive age before initiating long-term isoniazid therapy, particularly when combined with other antituberculous medications.