Clinical efficacy of leprerelin acetate with different dosage forms in central precocious puberty girls

Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.

Treatment of central precocious puberty by GnRH analogs： long-term outcome in men

In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.

Rare mutation in MKRN3 in two twin sisters with central precocious puberty: Two case reports

BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.

Efficacy and Safety of Domestic Leuprorelin in Girls with Idiopathic Central Precocious Puberty： A Multicenter,Randomized, Parallel, Controlled Trial

Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.

Prevalence of vitamin D deficiency in girls with idiopathic central precocious puberty

The relationship between vitamin D deficiency and idiopathic central precocious puberty （ICPP） has been recently documented. In this study, 280 girls diagnosed with ICPP and 188 normal puberty control girls of similar ages were enrolled and retrospectively studied. The ICPP group had significantly lower serum 25- hydroxyvitamin D （25[OH]D） levels than the control group. Furthermore, a nonlinear relationship was found between serum 25[OH]D and ICPP, and a cut-offpoint for serum 25[OH]D was found at 31.8 ng/ml for ICPP with and without adjusting the different confounding factors. Girls with serum 25[OH]D 〉~ 31.8 ng/ml had a lower odds ratio （unadjusted： OR 0.36, 95% CI 0.15 to 0.83, P 〈 0.05; height and weight adjusted： OR 0.44, 95~0 CI 0.18 to 1.08, P = 0.072; BMI adjusted： OR 0.36, 95% CI 0.16 to 0.84, P 〈 0.05）. The ICPP subjects with 25[OH]D deficiency had a higher body mass index （BMI） than the subjects from the two other subgroups. Correlation analysis showed that vitamin D level is correlated with BMI and some metabolic parameters in the ICPP group. Our study suggested that vitamin D status may be associated with ICPP risk and may have a threshold effect on ICPP.

Central precocious puberty as a prelude of gonad dysplasia

There is increasing evidence that patients with gonad dysplasia,as characterized by absent or incomplete puberty,can also exhibit central precocious puberty(CPP).Herein,we review the reported cases that manifest with both gonad dysplasia and CPP.Further,we examine the hypothesis that these patients exhibit a normal hypothalamic-pituitarygonadal axis,hypogonadism,and the presence of residual gonadal function,and that the onset of disease is related to early initiation of the hypothalamic-pituitary-gonadal axis.Thus,we suggest that CPP is a prelude of some partial hypogonadism.

Independent Relationship between Body Mass Index and LH Peak Value of GnRH Stimulation Test in ICPP Girls: A Cross-sectional Study

The effect of obesity on idiopathic central precocious puberty（ICPP） girls is still under discussion. The relationship between body mass index（BMI） and sexual hormone levels of gonadotropin-releasing hormone（GnRH） stimulation test in ICPP girls is controversial and the underlying mechanism is unclear. This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone（LH） level of stimulation test in ICPP girls and the role of other related factors. A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP, including 355 cases of normal weight, 99 cases of overweight and 164 cases of obese. The results showed that obese group had more progressed Tanner stage and no significant difference（P=0.28） in LH peak was found as basal LH value was used as a covariate. The obese group had higher total testosterone（TT）, adrenocorticotrophic hormone（ACTH）, 17-α hydroxyprogesterone（17-αOHP） and androstendione（AN）, with significantly increased fasting insulin（FIN） and homeostasis model of assessment for insulin resistance index（HOMA-IR）. Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score（BMI-SDS） and LH peak in different Tanner stages（P for interaction=0.017）. Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages. Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages, with and without different confounding factors being adjusted. In B2 stage, BMI-SDS was negatively associated with LH peak. In B3 stage, when BMI-SDS 〈1.5, as BMI-SDS increased, the level of LH peak decreased（model Ⅰ： β=–1.8, 95% CI=–4.7 to 1.1, P=0.214）. When BMI-SDS ≥1.5, BMI-SDS was significantly positively associated with LH peak（model Ⅰ： β=4.5, 95% CI=1.7 to 7.4, P=0.002）. In B4 stage, when BMI-SDS 〈1.5, BMI-SDS was negatively associated with LH peak（model Ⅰ： β=–11.6, 95% CI=–22.7 to –0.5, P=0.049）. When BMI-SDS ≥1.5, BMI-SDS was positively associated with LH peak（model Ⅰ： β=–4.2, 95% CI=–3.3 to 11.7, P=0.28）. It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls, their relationships are different in different Tanner stages, and the effect of BMI-SDS can be affected by adrenal androgens, estradiol and glucose metabolism parameters.