The Safety And Efficacy Of GnRH Pump Treatment In Hypogonadotropic Hypogonadism

BackgroundThere are three approaches to treat hypogonadotropic hypogonadism(HH): sex hormone replacement therapy,gonadotropin therapy,Gn RH pulsatile pump therapy. The Gn RH pulsatile pump therapy can simulate human physiological model by pulsative releasing Gn RH analogues,to start puberty,to promote and maintain the secondary sexual characteristics,eventually to achieve fertility. Gn RH pump has unique advantage in the treatment of HH.ObjectiveTo study the safety and efficacy of Gn RH pump treatment in hypogonadotropic hypogonadism,and to explore the related influencing factors of Gn RH pump.Methods34 cases with hypogonadism were referred to Pediatrics Endocrinology from 2012 January to 2015 January. After examinations of sex hormones,15 cases of Turner syndrome,namely hypergonadotropic hypogonadism were excluded. 19 cases of HH were eligible for the study to carry the Gn RH pump. With self-control,mutual-control retrospective study,through the subcutaneous implant of Gn RH pump infusing gonadotropin releasing hormone,hormone levels(follicle stimulating hormone,luteinizing hormone,testosterone)before and after treatment,the development of secondary sexual characteristics situation(to the male :testicular volume,penile length,whether the voice begin to change,beard and pubic hair appear,to the female: the breast growth,menstrual cramps),pelvic or testicular ultrasound,and the complain of patients and their families are used as evaluation of the therapeutic effect. By observing the HH patients of carrying the Gn RH pump dynamically,adverse reactions of Gn RH pump are recorded,then analysed,to evaluate the safety of Gn RH pump in use. To investigate whether the HH complicated with pituitary hormone deficiency,the Gn RH stimulation test results before treatment,BMI index are influencing factors of Gn RH pump’s therapeutic effect.All the observation data and laboratory tests data are processed by SPSS17.0 statistical software. For non-normal distribution data,the median(the twenty-fifth percentile,the seventy-fifth percentile) is the form of describing statistics,nonparametric test acts as statistical deduction; for normal distribution data,standard ±deviation is the form of describing statistics,t-test or analysis of variance serve as statistical deduction.Results1 19 cases of HH were studied,including 17 cases male patients,2 cases female patients,whose age between 12-27 years old,average 20.65±3.98 years old. The serum FSH level in male patients before treatment,1 months after treatment,2 months after treatment,3 months after treatment,6 months after treatment are 0.71(0.43,1.875)m IU/ml,1.73(1.02,3.27)m IU/ml,3.87±3.41 m IU/ml,2.69(1.475,5.935)m IU/ml,4.46± 3.26 m IU/ml respectively. The serum LH level before treatment,1 months after treatment,2 months after treatment,3 months after treatment,6 months after treatment are 0.38(0.12,0.905)m IU/ml,1.22(0.7,3.035)m IU/ml,2.91 ±2.84 m IU/ml,3.27 ±3.04 m IU/ml,4.66±4.36 m IU/ml respectively. The level of serum testosterone in male patients before treatment,1 months after treatment,2 months after treatment,3 months after treatment,6 months after treatment are 0. 03(0.015,0.175)ng/ml,0.13(0.03,0.625)ng/ml,0.26(0.065, 0.785)ng/ml,0.65(0.04,1.90)ng/ml,2 ±1 ng/ml. Testicular volume of male patients before treatment,1 months after treatment,2 months after treatment,3 months after treatment,6 months after treatment are 3(3,4)ml,5.29±3.50 ml,7.14±4.85 ml,8.29±5.62 ml,12.57±7.85 ml. Penile length of male patients before treatment,1 months after treatment,2 months after treatment,3 months after treatment,6 months after treatment are 3.29±0.92 cm,4(3.25,4.5)cm,4.31±1.17 cm,4.76±1.83 cm,5.57±1.57 cm respectively.2 The FSH level,LH level,testicular volume,penile length of male patients in the first months,in the second months,in the third months,in the sixth months after treatment are increased significantly compared to those of the initial condition(P< 0.05). Testosterone level in male patients before and after treatment were no statistically significant difference(P> 0.05).3 2cases of female HH patient complicated with pituitary hormone deficiency,one case of whom heals namely. Her indexes of FSH level before treatment,1 month after treatment,6 months after treatment were 0.66 m IU/ml,7.07 m IU/ml,3.26 m IU/ml respectively. Her indexes of LH levels were 0. 16 m IU/ml,4.41 m IU/ml,1.83 m IU/ml respectively,Her indexes of E2 levels were0.09pg/ml,139.7pg/ml,5pg/ml respectively. After treatment the development of her uterus,ovaries and breasts is significantly. Another case yield poor results.4 The patients were divided into the HH complicated with multiple pituitary hormones deficiency group and the HH not complicated with multiple pituitary hormones deficiency group. Male patients’ indexes of FSH level,testicular volume,penile length after treatment analysed by Wilcoxon rank sum test respectively. Male patients’ indexes of LH level after treatment are processed by independent samples t test. Research shows that there is no statistical significance(P> 0. 05)between the two groups,we come to the conclusion that whether the patients complicated with pituitary hormone deficiency is not the influence factor of the Gn RH pump therapy effect.All the cases were divided into three groups depending on the Gn RH stimulation test results,which were the good group,the medium group and the poor group. Male patients’ indexes of FSH,LH,T,testicular volume,penile length level after treatment are processed by K-W H test respectively(P > 0. 05). Research shows that there is no statistical significance(P > 0.05)among the three groups. We come to the conclusion that Gn RH stimulation test result is not the influence factor of the Gn RH pump therapy effect.All the male patients were divided into 2 groups based on the BMI(body mass index),which were the BMI<24 group and the BMI≥ 24 group. Male patients’ indexes of FSH level,T level after treatment are analysed by Wilcoxon rank sum test respectively. Male patients’ indexes of LH level,testicular volume,penile length after treatment are processed by independent samples t test. Research shows that there is no statistical significance(P > 0.05)between the two groups,we come to the conclusion BMI is not the influence factor of the Gn RH pump therapy effect.5 For each patient,the application of Gn RH pump usually start from small doses,i. e. 5μg/90 min. Hormone level and sexual development index of patients are tested monthly during the follow-up we should increase the dosage and frequency. We find that individualized approach to patients should now be adopted by dosage adjustment based on the clinical data,.Conclusions1 Preliminarily Gn RH pump is safe and effective in hypogonadotropic hypogonadism.2 The results of Gn RHa stimulating tests play an important role in making treatment plan for HH patients. Even if it has not reached the peak of LH>5.0IU/L and LH/FSH>0.6,Gn RH pump is available if LH peak increased significantly compared with basal value.3 5ug/min can be initial dose and then Gn RHa dose and frequency should be adjusted according to the level of sex hormone and gonadal development.4 Effect of Gn RHa pump is different in different patients. Those such as application of hormone replacement before Gn RH pump,gonadotropin and sex hormone receptor interaction strength and so on,may have influences on effect of pump.