The Efficacy And Safety Of Gnrh Pulsatile Subcutaneous Infusion In Adolesents With Hypogonadotropic Hypogonadism

Background and objective:Delayed puberty is defined as the absence of signs of sexual maturation by an age more than 2-2.5 SD values above the mean of the population,ie.by 13 years old in girs and 14 years old in boys.Some belong to constitutional delay of growth and puberty.Others are hypergonadotropic hypogonadism and hypogonadotropic hypogonadism.By far,there are 3 types of approaches to treat hypogonadotropic hypogonadism(HH):sex hormone replacement therapy,gonadotropins therapy,and pulsatile GnRH subcutaneous trerapy.All of them have their own advantages and disadvantages.Only a few cases of females in the third approache have been reported.This research was going to observe hormone variation,secondary sex characteristics change before and during the treatment and adversereactions of patients who had taken the therapy,and report case informations,then research the safety and efficacy of pulsatile GnRH subcutaneous therapy by GnRH pump in hypogonadotropic hypogonadism.Evaluation of advantages and disadvantages,discussing the problems were also the aim.Research objects and methods:7 patients with HH who agreed to accept the pulsatile treatment were included in this research,including 4 females and 3 males.Mean ages are(18.43±3.50)yr.5 patients were with multiple pituitary hormone deficiency(MPHD),including 3 patients with pituitary stalk interruption syndrome(PSIS),1 patient whose pituitary MRI showed the signal of neurohypophysis was not obvious,1 patient was diagnosed as Kallmann syndrome.And 1 patient was with isolated hypogonadotropic hypogonadism.All the patients were given pulsatile GnRH subcutaneous therapy.Through the subcutaneous implant of GnRH pump infusing gonadotropin releasing hormone,hormone levels before and after treatment,the development of secondary sexual characteristics situation,ultrasound,and the feelings of the patients were recorded and collected.In the end of test period(7days after therapy),FSH and/or LH ?1mIU/ml was regarded as evaluation of the therapeutic effectivity.The long-term efficacy was evaluated by hormone levels,the development of secondary sexual characteristics situation,ultrasound,and the feelings of the patients.Result:The mean of 60min LH of the GnRH stimulating test was(1.68±2.39)mIU/ml.In the end of test period,The basal FSH was(4.53±2.70)mIU/ml.The basal LH was(1.47±0.87)mIU/ml.The max of FSH was(4.81±2.62)mIU/ml.The max of LH was(1.65±0.77)mIU/ml.LH/FSH was(0.43±0.22).By the end of the first month of treatment,the basal FSH was(5.28±3.25)mIU/ml;The basal LH was(2.65±1.07)mIU/ml;The max of FSH was(6.22±3.76)mIU/ml;The max of LH was(4.21±1.08)mIU/ml.LH/FSH was(0.87±0.43).The LH in the end of first month increased significantly compared to that of the end of test period(P<0.05),while FSH not.The LH in the end of first month increased compared to that of test period but not significantly(P>0.05).FSHmax was increased significantly compared to basal one(P<0.05),and r=0.92.LHmax was increased significantly compared to basal one(P<0.05),and r=0.94.The secondary sex characteristics of all the patients developed.1 male reported erection and emission,1 female felt her breast bigger.During the treatment,1 male patient's estradiol was so high that he was given letrozole.1 patient reported red and swelling of the injection site,and was better when treatment.By the end of the research,1 patient has taken treatment more than 2 years.In the end of the second year,his FSH,LH were still good.Conclusions:1.pulsatile GnRH subcutaneous therapy by pump is safe and effective in adolesents with hypogonadotropic hypogonadism;2.The LH in the end of first month was increased significantly compared to that of the initial condition(P<0.05);FSH was also increased,but not significantly.3.During the treatment,basal FSH was correlated with FSHmax,and so was LH.