OBJECTIVE Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH). DESIGN Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA. METHODS Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring. RESULTS AND CONCLUSIONS Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2 and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, and 1.0 mg groups respectively, vs 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean -1.24%, -1.30%, -2.09%) and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function. CLINICAL TRIAL REGISTRATION NUMBER NCT02730169.

中文翻译：

---

来氟曲唑治疗男性肥胖相关低促性腺激素性性腺功能减退症：Ph 2b 双盲随机对照试验。

目的 评估芳香酶抑制剂来氟曲唑使肥胖相关低促性腺激素性性腺功能减退症 (OHH) 睾酮正常化的有效性和安全性/耐受性。设计 在欧洲/美国 70 个地点进行安慰剂对照、双盲、随机对照试验。方法 患者纳入标准：BMI为30-50 kg/m2、早晨总睾酮（TT）<10.41 nmol/L、有两种雄激素缺乏症状（至少一种性功能障碍）的男性。患者随机接受每周一次的左氟曲唑（0.1/0.3/1.0 mg）或安慰剂，为期 24 周。主要终点：24 周后，≥75% 的患者 TT 水平恢复正常。次要终点（包括）：TT 正常化时间和 LH/FSH 变化。通过不良事件和实验室监测评估安全性。结果和结论 在 2103 名筛查对象中，271 名被随机分配，81 名被终止。各组的人口统计特征相似。平均 BMI 为 38.1 kg/m2，TT 为 7.97 nmol/L。所有来氟曲唑治疗组均在 24 周内通过剂量分级反应实现了主要终点；平均 TT 15.89；17.78；来氟曲唑 0.1 mg、0.3 mg 和 1.0 mg 组分别为 20.35 nmol/L，而安慰剂组为 8.04 nmol/L。与安慰剂组相比，来氟曲唑组的 LH/FSH 显着增加。没有观察到身体成分或性功能障碍的改善。与安慰剂相比，来氟曲唑改善了精液量/活动精子总数。治疗中出现的不良事件在来氟曲唑治疗组中更为常见，包括红细胞压积升高、高血压、PSA 升高和头痛。0.1 mg、0.3 mg、1.0 mg 和安慰剂组观察到左氟曲唑腰椎骨密度有所降低（平均值分别为 -1.24%、-1.30%、-2.09%）和 0.66%，而髋部没有变化。来氟曲唑在 OHH 中的随机对照试验证明了肥胖男性的 TT 正常化。FSH/LH 和精液参数变化支持来氟曲唑可以保留/改善睾丸功能。临床试验注册号NCT02730169。