Male reproductive hormones in patients treated with pretomanid

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.