Glucose And Lipid Metabolism And Function Of Hypothalamic Pituitary Gonadal Axis Of Girls With ICPP After GnRHa Treatment: A Two-year Follow-up

Objective The aim of this study was to observe the influence on(body mass index) BMI,glucose and lipid metabolism and hypothalamic pituitary gonadal axis(HPGA)function of the girls with idiopathic central precocious puberty(ICPP), who had been treated with gonadotropin-releasing hormone analogue(GnRHa) and GnRHa withdrawal.Method A prospective study was performed involved 76 girls with ICPP(41 treated with GnRHa for 2.4±0.57 years and withdrawal, 35 untreated) from Mar 2013 to Feb2014 in Fuzhou Children`s Hospital of Fujian Province, while 71 girls(41 treated,30 untreated) completed two years follow-up. Height and weight of all girls were measured and the development of breast and pubic hair were evaluated according to the Tanner standard yearly. Meanwhile fasting blood glucose(FBG), triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), insulin(INS), luteinizing hormone(LH),follicle stimulating hormone(FSH), estradiol(E2), testosterone(T),dehydroepiandrosterone sulfate(DHEAS), sex hormone-binding globulin(SHBG)and androstenedione(AND) were detected. The volume of uterine and ovarian of all cases was observed using pelvic ultrasound and bone age(BA) were evaluated. BMI,BMI SDS and homeostasis model assessment of insulin resistance(HOMA-IR) were calculated. All statistics were analyzed with SPSS 22.0 statistical software. Mixed linear model, Independent samples T test, Mann-Whitney U test, Friedman M test,Chi-square test and Pearson's correlation were applied.Results1. At the beginning of follow-up, the average age of girls treated with GnRHa for(2.4±0.57)yr was(10.41±0.73) years old and BA was(11.90±0.82) years old,while the average age of untreated girls was(8.43 ±0.84) years old and BA was(10.75±1.17) years old. All enrolled girls(41 treated with GnRHa, 35 untreated)came to our clinical at 1 year follow-up, while 5 untreated girls lose to follow at 2years.2. During the follow-up, the difference between GnRHa treated and untreated girls in BMI, BMI SDS, FBG, INS, HOMA-IR, TG, TC, HDL-C, LDL-C, LH,DHEAS, AND, SHBG or T had no statistical significance(P>0.05). At 1 year follow up, the volume of uterine and ovarian of GnRHa treated girls was lower than that of untreated grils(P<0.05), while no statistically significant difference was found at 2years follow-up(P>0.05).3. BMI, INS, HOMA-IR, TG, HDL-C, LH, FSH, E2, DHEAS, AND and the volume of uterine and ovarian of both groups among different years had statistically significant differences(P<0.05), while BMI SDS, FBG, TC, LDL-C, SHBG and T had no statistical difference(P>0.05).4. Analysis of mixed linear model showed that significant interaction between groups and different years was found in HDL-C, FSH, DHEAS and the volume of uterine and ovarian(P<0.05), but not in BMI, BMI SDS, FBG, INS, HOMA-IR, TG,TC, LDL-C, LH, AND or SHBG(P>0.05).5. The girls treated with GnRHa who emerged menarch(14.52±4.88) months after withdrawal, had older age at menarch than untreated girls[(11.66±0.65) years vs.(9.62±0.74) years, P<0.05]. One ovarian cyst in the right ovary of an untreated girls was detected by pelvic ultrasouond at the 1.5 years follow-up, and disappeared after6 months interval without treatment.Conclusion During the follow-up, no matter whether GnRHa therapy or not, BMI of ICPP girls increased with age, but BMI SDS had no obvious change. GnRHa had no affect on BMI, BMI SDS, glucose and lipid metabolism of ICPP girl within 2 years afterwithdrawal. The HPGA function of ICPP girls treated with GnRHa recoveried within1 year after GnRHa withdrawal, at the same time, the volume of uterine and ovarian increased significantly. DHEAS and AND of both groups increased during the follow-up, but it was not associated with GnRHa.