Effects Of GnRHa On Ovarian Reserve Function In CPP Girls

ObjectiveTo explore the effect of Gonadotropin releasing hormone analogue(GnRHa)on ovarian reserve function in girls with central precocious puberty(CPP),the relationship has been analyzed between anti-Mullerian hormone(AMH)and drug species,dosage,treatment course,luteinizing hormone(LH)levels,follicle stimulating hormone(FSH)levels,estradiol(E2)levels and uterine and ovarian volumes.The effects of GnRHa treatment on reproductive ability of CPP girls can be predicted in early stage,which can eliminate the concerns of children and parents and improve the compliance of GnRHa treatment in children with central precocious pubertyMethodThe clinical data of CPP girls treated with GnRHa for more than half a year in our hospital were retrospectively collectedin recent 10 years.These data included serum LH levels,FSH levels,FSH/LH levels,E2 levels,AMH levels,ovarian volumes(Vov),uterine volumes(Vut)at different time points during the GnRHa treatment and menarche(or menstrual resurgence).Data of GnRHa species,dosage and course of treatment had also been collected.A total of 383 CPP girls were treated with GnRHa,among them,triptorelin were used in 253 cases,leuprorelin in 130 cases.and 221 cases had finished the treatment.The subjects were divided into triptorelin group and leuprorelin group,and the effects of the two drugs on LH,FSH,FSH/LH,E2,AMH,Vut and Vov were analyzed.The effects of GnRHa on ovarian reserve function of CPP girls were analyzed by the change tendencies of the above indicators.The correlations were explored between AMH and LH,FSH,FSH/LH,E2,Vut,Vov,drug varieties,dosage and course of treatment.Result1.The initial data were no differences between triptorelin group and leuprorelin groupin LH,FSH,AMH,LH max,FSH max,FSH/LH max levels,Vut and Vov(p>0.05),except E2.Before treatment,the E2 in Triptorelin group was higher than that in leuprorelin group(110.31±107.54 VS 86.09±80.97,t=2.265,p=0.024).There was no significant difference between two groups in LH,FSH,AMH,uterine and ovarian volume at each time point(p>0.05).The decrease of E2 levels in triptorelin group was greater than that in leuprorelin group at each time point with significant differencesat 6 months of treatment(-82.52±92.55 VS-60.96±83.63,t=-2.149,p=0.032)and 30 months of treatment(-60.01 ±68.69 VS-31.26±38.98,t=-2.486,p=0.015)2.The effects of GnRHa treatment were similaron ovarian reserve function index such as uterine and ovarian volume,LH,FSH and E2,all of which were inhibited in the course of treatment compared with those before treatment(p<0.05),after drug withdrawal,those levels recovered gradually.And at menarche after with drawal,the indicators were higher than those before treatment(LH?FSHlevels,p<0.05,but E2,Vut and Vov,p>0.05).There was a transient decrease of AMH at 6 months after GnRHa treatment(2.70+1.76 VS 3.56+2.21,t=3.227,p=0.001),but the levels of AMH in 12,18,24 months after GnRHa treatment were similar to those before treatment(p>0.05).The FSH/LH value increased significantly from 12 months after treatment to the time of discontinuation of drugs compared with initial FSHmax/LHmax(p<0.05),the FSH/LH at menache were significantly lower than initial basal FSH/LH values(1.34±0.66 VS 5.69±6.85,t?3.068,p=0.006).3.Using FSH/LH and FSH levels as ovarian reserve function index,the percentage of normal ovarian reserve function in children with CPP at menstrual onset was higher than that before treatment(percentage of normal FSH/LH levels were 100%VS 46%,?2=27.586,p<0.05;FSH levels were not significantly different,100%VS 99%,p>0.05).Using AMH levels as ovarian reserve function index,and percentage of normal ovarian reserve function at menstrual onset was slightly lower than that before treatment(87%VS 93%),but there was no significant difference(p>0.05)4.There was no correlation between AMH and LH,E2,treatment dosage(p>0.05),but AMH was positively correlated withthe course of treatment(r=0.340,p<0.05).There was a positive correlation between AMH and Vut and FSH at 6 months of treatment(r value were 0.533,0.252,respectively,p<0.01),but no correlation between AMH and Vut after 6 months of treatment(p>0.05),and a negative correlation with FSH and FSH/LH after that(r value were negative,p<0.01).AMH and Vovwere positively correlated during the first 24 monthes of theatment(r werepositive,p<0.05),but not after that(p>0.05)Conclusion1.The ovarian reserve function of CPP girls was inhibited to some extent during GnRHa treatment,but recovered gradually after with drawal,and it was not inferior to the initial when menstruation came.2.During GnRHa treatment,AMH is a good index to reflect ovarian reserve function.It is not affected by LH,E 2 and treatment dosage,positively correlated with age and ovarian volume,but negatively correlated with FSH and FSH/LH levels.3.Triptorelin and leuprorelin have similar effects on ovarian reserve function in CPP girls.4.The ovarian reserve function of children can be assessed at early stage through the study of the change tendencies of Vuv,Vov,LH,FSH,FSH/LH,E2 and AMH levels,which can eliminate parents' concems about side effects of treatment and improve the compliance of GnRHa treatment.