Brown University, Providence, Rhode Island, USA.
TB Alliance, Pretoria, South Africa.
Int J Tuberc Lung Dis. 2022 Jun 1;26(6):558-565. doi: 10.5588/ijtld.21.0654.
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 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. 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. 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. 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.
丙硫异烟胺（Pa）是一种硝基咪唑类药物，最近获得美国食品和药物管理局及其他监管机构批准，纳入方案用于治疗高度耐药性肺部感染。在啮齿动物中的研究将睾丸确定为关注的靶器官，这导致对纳入四项丙硫异烟胺方案临床试验和含异烟肼+利福平+吡嗪酰胺+乙胺丁醇（HRZE）对照方案的 >800 名男性患者进行生殖激素监测。四项临床试验中汇总了与男性生殖健康相关的血清激素水平——卵泡刺激素（FSH）、黄体生成素（LH）、抑制素 B（InhB）和总睾酮（T）——并通过重复测量模型进行分析。激素水平在丙硫异烟胺组和 HRZE 组中通常表现相似。与基线相比，治疗结束时和随访时血清 T 和 InhB 水平通常升高。FSH 和 LH 水平变化不定，但随访时通常处于或低于基线水平。治疗前，许多患者处于边缘性性腺功能减退状态，T 水平接近正常范围的下限。四项研究结核病患者的男性激素变化表明，丙硫异烟胺治疗与睾丸毒性无关，而是导致潜在的性腺功能减退得到改善。
