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. 2022 Jun 1;26(6):558-565.
doi: 10.5588/ijtld.21.0654.

Male reproductive hormones in patients treated with pretomanid

K Boekelheide  1 , M Olugbosi  2 , J Nedelman  3 , D Everitt  3 , E Smith  3 , M Betteridge  3 , E Sun  3 , M Spigelman  3
Affiliations

Male reproductive hormones in patients treated with pretomanid

K Boekelheide et al. Int J Tuberc Lung Dis. .

Abstract
in English, French

BACKGROUND: Pretomanid (Pa) is a nitroimidazole-class drug recently approved by the US Food and Drug Administration and other regulatory authorities as part of a regimen for treating highly drug-resistant pulmonary Mycobacterium tuberculosis infections. Studies in rodents identified the testis as a target organ of concern, which led to monitoring of reproductive hormones in >800 male patients enrolled in four clinical trials of Pa-containing regimens and the HRZE (isoniazid+rifampin+pyrazinamide+ethambutol) control regimen.METHODS: Serum hormone levels relevant to male reproductive health - follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B (InhB) and total testosterone (T) - from the four clinical trials were summarized numerically and analyzed by repeated-measures modeling.RESULTS: Hormone levels generally behaved similarly in Pa-containing and HRZE arms. Relative to baseline, serum T and InhB levels generally increased at the end of treatment and follow-up. FSH and LH levels were variable, but were generally at or below baseline levels by follow-up. Before treatment, many patients were borderline hypogonadal, with T levels near the lower limits of the normal range.CONCLUSION: Changes in male hormones in four clinical trials studying patients with TB indicate that Pa-containing treatment was not associated with testicular toxicity but rather led to improvement in the underlying hypogonadism.

CONTEXTE :: Le prétomanide (Pa) est un médicament de la classe des nitroimidazoles, récemment homologué par la FDA américaine et d’autres autorités réglementaires comme agent d’un schéma thérapeutique pour les infections pulmonaires à Mycobacterium tuberculosis hautement résistant aux antituberculeux. Les études réalisées chez les rongeurs ont permis d’identifier les testicules comme organes cibles préoccupants, entraînant la surveillance des hormones de reproduction chez >800 hommes inclus dans quatre essais cliniques visant à évaluer les schémas à base de Pa et le schéma de contrôle à base d’HRZE (isoniazide+rifampicine+pyrazinamide+ethambutol).

MÉTHODE :: Les taux sériques d’hormones pertinentes à la santé reproductrice de l’homme (hormone folliculo-stimulante [FSH], hormone lutéinisante (LH), inhibine B [InhB] et testostérone totale [T]) issus des quatre essais cliniques ont été synthétisés numériquement et analysés à l’aide de modélisations à mesures répétées.

RÉSULTATS :: Les taux d’hormones étaient généralement similaires entre les groupes sous schéma à base de Pa et sous schéma à base de HRZE. Par rapport à l’inclusion, les taux de T et d’InhB avaient tendance à augmenter à la fin du traitement et pendant le suivi. Les taux de FSH et de LH étaient variables mais, au moment du suivi, ils étaient généralement similaires ou inférieurs aux taux observés à l’inclusion. Avant le traitement, de nombreux patients étaient à la limite de l’hypogonadisme, avec des taux de T proches de la limite inférieure de la normale.

CONCLUSION :: Les variations des taux hormonaux observées chez l’homme dans le cadre de quatre essais cliniques évaluant des patients atteints de tuberculose, indiquent que le traitement à base de Pa n’est pas associé à une toxicité testiculaire mais plutôt à une amélioration de l’hypogonadisme sous-jacent.

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Conflict of interest statement

Conflicts of interest: KB has been a paid consultant to TB Alliance since 2013, providing his expertise in male reproductive tract toxicity and the clinical assessment of male reproductive tract function. He received no compensation for his effort in performing the background research, data integration, and writing of this manuscript.

Figures

Figure
Figure
NC-006: percentage change in hormones from baseline comparing Pa100MfxZ-17 weeks (drug-susceptible TB) vs. PA200MfxZ-17 weeks (drug-susceptible TB). Dots are point estimates and vertical lines span 95% confidence intervals. Black lines = Pa100MZ; gold lines = Pa200MZ; FSH = follicle stimulating hormone; LH = luteinizing hormone; EOT =end-of-treatment.
See this image and copyright information in PMC

Comment in

References

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