GnRH泵治疗卡尔曼综合征男性患者的有效性和安全性研究

Efficacy and safety of GnRH pulsatile subcutaneous infusion in male patients with Kallmann syndrome

目的通过观察促性腺激素释放激素(GnRH)泵皮下脉冲输注治疗男性卡尔曼综合征(Kallmann syndrome,KS)患者治疗前后的第二性征发育情况、激素水平变化及不良反应,探讨戈那瑞林皮下脉冲治疗的有效性和安全性。方法纳入20例2012年3月至2019年6月解放军总医院第一医学中心确诊并自愿接受GnRH泵治疗的KS患者作为研究对象,观察治疗前、试戴期末(戴泵后第7天)、3个月、6个月及1年以上随访中促性腺激素、睾酮、睾丸超声、体征及自我体验的不同。结果所有患者均进行了GnRH兴奋试验,60 min黄体生成素(LH)均值为(3.00±2.96)U/L。戴泵治疗1周时,LH[(12.30±11.95)U/L比(0.27±0.24)U/L,P<0.05]和卵泡刺激素[(4.99±2.84)U/L比(0.92±0.69)U/L,P<0.05]水平较基线水平显著升高。治疗半年和末次随诊时睾酮水平分别为(7.06±5.22)mmol/L和(9.78±8.10)mmol/L,均较基线水平[(1.46±1.40)mmol/L]显著升高(P均<0.01)。睾丸容积逐渐增大,治疗半年后,双侧睾丸容积之和(BTV)从(3.03±3.54)ml增加至(4.94±1.34)ml(P<0.05),末次随诊时,BTV达到(16.20±8.37)ml。所有患者的第二性征均有不同程度的改善,3例患者报告注射部位红肿不适,经对症处理后好转。结论GnRH泵皮下脉冲输注戈那瑞林治疗KS患者安全有效。

Objective To investigate the efficacy and safety of subcutaneous pulse therapy with gonadorelin by observing the development of the secondary sexual character,hormone variations and adverse reactions in male patients with Kallmann syndrome(KS)before and after subcutaneous pulse infusion with gonadotropin releasing hormone(GnRH)pump.Methods 20 KS patients diagnosed and voluntarily treated with GnRH pump in the First Medical Center,Chinese PLA General Hospital between March 2012 and June 2019 were enrolled.The differences of gonadotropin,testosterone(T),testicular ultrasound,signs and self feeling were observed before treatment and 7 days,3 months,6 months and more than 1 year after treatment.Results GnRH stimulation test was carried out in all patients,and the mean value of 60 min luteinizing hormone(LH)was(3.00±2.96)U/L.The level of LH[(12.30±11.95)U/L vs.(0.27±0.24)U/L,P<0.05]and follicle-stimulating hormone(FSH)[(4.99±2.84)U/L vs.(0.92±0.69)U/L,P<0.05]were significantly higher than those of baseline after one week of pump wearing.T levels were(7.06±5.22)mmol/L and(9.78±8.10)mmol/L at half a year and the last follow-up,respectively,which were significantly higher than the baseline level[(1.46±1.40)mmol/L,all P<0.01].The testicular volume increased gradually.Half a year after treatment,the bilateral testicular volume(BTV)increased from(3.03±3.54)ml to(4.94±1.34)ml(P<0.05).At the last follow-up,BTV rose to(16.20±8.37)ml.The secondary sexual character of all patients were improved to some extent.Three patients reported that the injection site was inflamed and uncomfortable,and relieved after symptomatic treatment.Conclusion Subcutaneous pulse infusion of gonadorelin with GnRH pump is safe and effective in the treatment of KS patients.