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Pilot Study on the Effects of First-Line Antituberculosis Drugs and Their Combinations on Selected Reproductive

Elif Esra Uyar1, Bulent Yavuzer2, Mansura Babayeva3

  • 1Department of In Vitro Fertilization, Clinic of Gynecology and Obstetrics, Lokman Hekim Istanbul Hospital, Istanbul 34912, Turkey.

Life (Basel, Switzerland)
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Summary

First-line tuberculosis drugs can impact female rat fertility, potentially through endocrine changes rather than just oxidative stress. Pyrazinamide may offer some fertility protection, but this effect is context-dependent.

Keywords:
anti-mullerian hormoneantituberculosis agentsethambutolfemale infertilityisoniazidoxidative stressprolactinpyrazinamideratsrifampicin

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Area of Science:

  • Reproductive toxicology
  • Endocrinology
  • Pharmacology

Background:

  • The reproductive toxicity of combined first-line tuberculosis drugs is not well understood.
  • Rifampicin, isoniazid, pyrazinamide, and ethambutol are crucial for tuberculosis treatment but their effects on female fertility are uncertain.

Purpose of the Study:

  • To evaluate the effects of first-line antituberculosis drugs, alone and in combination, on oxidative stress, endocrine markers, and reproductive outcomes in female rats.
  • To investigate the potential role of oxidative stress and endocrine alterations in drug-induced reproductive impairment.

Main Methods:

  • Ninety-six female rats were administered single, dual, triple, or quadruple regimens of first-line antituberculosis drugs for 28 days.
  • Fertility was assessed after a 7-day cohabitation period with males.
  • Serum levels of malondialdehyde (MDA), total glutathione (tGSH), prolactin, and anti-Mullerian hormone (AMH) were measured.

Main Results:

  • Single drugs increased oxidative stress (MDA↑, tGSH↓) without causing infertility.
  • Dual, triple, and quadruple regimens induced significant oxidative imbalance.
  • Fertility failure was observed in pyrazinamide-lacking groups, associated with higher prolactin and lower AMH levels.
  • Fertility impairment was not solely explained by oxidative stress but also involved endocrine markers.

Conclusions:

  • Reproductive impairment from these antituberculosis drugs may involve endocrine alterations beyond oxidative stress.
  • Pyrazinamide showed potential context-dependent fertility preservation, warranting further investigation.
  • Larger mechanistic studies are needed to fully elucidate the reproductive and endocrine effects.