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Central precocious puberty (CPP) is a common pediatric endocrine disease caused by premature activation of the hypothalamic-pituitary-gonadal axis, featured by rapid development of internal and external reproductive organs and secondary sexual characteristics in girls before age 8 and boys before age 9.The gonadotropin-releasing hormone analogue (GnRHa) is the first choice for the treatment of CPP.Currently, 3.75 mg/ month sustained -release short-acting dosage form (1M depot formulations) is the most commonly used in China.The development of long-acting dosage form will reduce injection times and clinic visits.At present, the 3-month long-acting dosage form (11.25 mg 3M depot formulations) of Leprorelin microsphere has been approved in China.However, clinical practice experience of 3-month Leuprorelin acetate depot formulations is lacking in China.Therefore, in this paper, existing clinical evidence for this dosage form was reviewed to provide evidence-based medicine support for its clinical application.
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OBJECTIVES@#To systematically evaluate the effect of gonadotropin-releasing hormone analogue (GnRHa) treatment on the final adult height of children over 6 years of age with central precocious puberty (CPP) or early and fast puberty (EFP).@*METHODS@#PubMed, MEDLINE, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for related articles on GnRHa treatment for children with CPP or EFP. Stata 12.0 software was used to perform a Meta analysis of related data.@*RESULTS@#A total of 10 studies were included, and the total sample size was 720 children, with 475 children in the GnRHa treatment group and 245 children in the control group. The Meta analysis showed that compared with the control group, the GnRHa treatment group had significantly better final adult height (@*CONCLUSIONS@#GnRHa treatment is safe and effective in improving the final adult height of children over 6 years of age with CPP or EFP.
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Adult , Child , Humans , Body Height , Gonadotropin-Releasing Hormone , Puberty , Puberty, Precocious/drug therapyABSTRACT
Objective@#To investigate the long-term effects of GnRHa treatment on final height gain, gonadal function, and body mass index(BMI) in children with central precocious puberty(CPP) or early and fast puberty(EFP), and to explore the influencing factors of height gain and early predictors.@*Methods@#Fifty patients with CPP and 44 patients with EFP who were treated with GnRHa for more than 2 years were enrolled(80 females and 14 males). Body height, bone age, BMI, gonads hormone, uterus and ovarian volumes(female), testicular volume(male), and other parameters before and after treatment were measured.@*Results@#(1)For girls: GnRHa plus GH treatment gained more final height compared with GnRHa treatment [(10.69±5.73) cm vs (7.42±5.76) cm, P<0.05]. Height lost >5cm at the initial treatment benefited much more for the final height compared with height lost<5cm [(10.65±3.32) cm vs (6.51±3.40) cm, P<0.01]. The proportion of overweight/obesity decreased when reaching the final height compared with the initial treatment and stopping the treatment. Serum LH level, uterine and ovarian volume were significantly decreased after stopping treatment compared with before treatment, and increased half a year to 1 year after stopping treatment.100% of girls had menarche and 95% reached the regular cycle 3 years after stopping treatment.(2)For boys: GnRHa plus GH treatment and GnRHa treatment gained height by(8.78±5.2) and(7.99±4.82) cm, respectively. Serum LH level and testicular volume were significantly decreased after stopping treatment as compared with those before treatment, and increased for half a year to 1 year after stopping treatment.@*Conclusion@#GnRHa treatment can significantly improve the final height for girls with CPP and EFP. The patients with more height lost could gain more height, which can be used as a predictor of height gain.
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A retrospective study was conducted on one patient with postmenopausal hyperandrogenism. The postmenopausal female patient was found with significant hyperandrogenism ( total testosterone 6. 4 nmol/ L) and hirsutism, with normal adrenal androgen ( dehydroepiandrosterone-sulfate ) level. Computed tomography and ultrasound did not detect any ovarian and adrenal mass. Positron emission tomography revealed without high metabolic region, either. Ovarian and adrenal vein catheterization did not reveal any positive result. Obviously, ovary-derived hyperandrogenism was highly suspected, but the patient still refused any surgical exploration. After a trial of a single dose of gonadotropin releasing hormone analogue(GnRHa) triptorelin, increased testosterone level returned to normal along with decreasing level of gonadotropin. Multiple doses were needed for maintenance of testosterone at normal level with the intervals of 2 ～ 12 months. This response to the treatment was consistent with that of gonadotropin dependent hyperandrogenism.
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[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.
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Objective To explore the clinical value of gonadotropin-releasing hormone analogue (GnRH-a) by analyzing the efficiency of GnRH-a treatment for moderate and severe endometriosis after laparoscopic conservative operations.Methods Two hundred and sixty-five females who accepted laparoscopic conservative operation were enrolled in this study,and they were confirmed by pathology for ovarian endometriosis cyst,in phase Ⅲ andⅣ,47 patients had fertility desire.According to whether use the drug and auxiliary species the postoperative cases were divided into 5 groups:102 cases without endocrinal therapy(untreated group),GnRH-a group of 3 months in 64 cases,GnRH-a group of 6 months in 31 cases;gestrinone group of 3 months in 38 cases,and gestrinone group of 6 months in 30 cases.All patients were followed up for 2 years,observed drug clinical effects,remission rate,improvement rate,recurrence rate,pregnancy outcomes and side effects.Results The remission rate in GnRH-a group of 6 months and gestrinone group of 6 months was significantly higher than that in untreated group [83.9％ (26/31),73.3％ (22/30) vs.52.9％(54/102)],the remission rate in GnRH-a group of 6 months was significantly higher than that GnRH-a group of 3 months [64.1％ (41/64)],there was significant difference (P ＜ 0.05).The recurrence rate in GnRH-a group of 3 months,GnRH-a group of 6 months,gestrinone group of 6 months was significantly lower than that in untreated group [12.5％ (8/64),9.7％ (3/31),10.0％ (3/30) vs.27.5％ (28/102)] (P ＜ 0.05).The recurrence rate in gestrinone group of 6 months was significantly lower than that in gestrinone group of 3 months (P ＜ 0.05).The recurrence time of GnRH-a group of 3 months,GnRH-a group of 6 months,gestrinone group of 6 months was significantly longer than that in untreated group [(14.05 ± 1.97),(16.76 ± 1.53),(16.12 ±2.15)months vs.(12.85 ± 1.80)months] (P ＜0.05).The recurrence time of gestrinone group of 3 months and untreated group had no significant difference(P ＞ 0.05).The pregnancy rate of GnRH-a group and gestrinone group was higher than that in untreated group,but there was no significant difference (P ＞ 0.05).The rate of menopausal symptom in GnRH-a group was higher than that in gestrinone group [50.5％ (48/95) vs.16.2％ (11/68)].The rate of abnormal bleeding in vagina,acne and side-effect of aminotransferase in GnRH-a group were significantly lower than those in gestrinone group [1.1％(1/95) vs.7.4％(5/68),0 vs.8.8％(6/68),0 vs.5.9％(4/68)](P＜ 0.05).Conclusions Laparoscopic conservative operations combined with GnRH-a on treatment of moderate and severe ovarian endometriosis can significantly improve remission rate,decrease recurrence rate.GnRH-a or gestrinone for 6 months,the pregnancy rate increases.In addition the side reactions of the two medicine have statistic difference,which of GnRH-a is lower.
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Objective To assess the efficacy of gonadotropin-releasing hormone analogue(GnRHa)with or without recombinant human growth hormone(rhGH)treatment in Chinese short pubertal children with non-growth hormone deficiency.Methods Of 42 short pubertal children(14 males,28 females)without growth hormone deftcieney,the average age was(11.6±0.8)year.30 children were treated with slow release GnRHa with initial dose (100μg·kg-1·d-1,28d)and maintenance dose(60-80μg·kg-1·d-1,28d)labd rgGH with initial dose(0.15IU·kg-1·d-1)and maintenance dose(0.10-0.15IU·kg-1·d-1)for at least 1year.16 of them were still ongoing till the end of the second year.12 children were treated with GnRHa alone by initial dose(100μg·kg-1·d-1,28d)and maintenance dose (60-80μg·kg-1·d-1,28d),and 7 of them remained on it for 2 years.Dynamic changes including annual growth velocity(GV),bone age(BA)/chronologic age(CA)ratio,Tanner stage,height SDS for CA (HtSDSCA),height SDS for BA(HtSDSBA),and predicted adult height (PAHSDS)were observed.Results By the end of the first year tretment with combination therapy,the following parameters:GV,HtSDSCA,HtSDSBA,and PAHSDS all increased significantly(all P<0.05).Treatment with GnRHa alone did not yield significant changes in GV,HtSDSCA,HtSDSBA,and PAHSDS(all P>0.05).Changes in GV,HtSDSBA,and PAHSDS between these two groups were statistically significant(all P<0.05).By the end of the second year treatment,in the combination group,GV slowed from 6.7 to 5.5 cm/year(P<0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P<0.05).In the group with GnRHa treatment alone,GV slowed from 4.0 to 3.6 cm/year(P>0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P>0.05).Changes in GV,HtSDSCA,HtSDSBA,and PAHSDS between these 2 groups were statistically significant respectively(all P<0.05).Conclusion This combined treatment regimen significantly impreved the growth by increasing growth rate and delaying bone matumtion in pubertal chidren without growth hormone deficiency.Further study is needed to verify beneficial effects on the final height gain.
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Objective To evaluate the long-term final adult height outcome of combined treatment with gonadotropin-releasing hormone analogue(GnRHa)and recombinant human growth hormone(rhGH)in girls with idiopathic central precocious puberty(ICPP).Methods Out of 49 sirls with ICPP[treated with GnRHa at a dose of 60-80 μg/kg every 4 weeks for at least 6 months,whose height velocity fell below 4 cm/year and showed no improvement of predicted adult height(PAH)in 6 months],26 received(rhGH-combined group),in addition to chronological age,and duration of GnRHa treatment,who showed the same growth pattern but refused rhGH treatment,served to evaluate the efficacy of rhGH in addition.At the conclusion of the smdy,all the girls had been followed up for(3.3±1.9)years,and(3.2±0.9)years in rhGH-combined group and control group,respectively;and had achieved adult heisht.To compare the PAH with the final adult height(FAH)before and after treatment in the two groups.Results During rhGH treatment, height velocity of the rhGH-combined girls increased significantly[(6.7±2.0 vs <4)cm/year baseline],RhGH-combined gids showed an adult height far higher than pretreatment PAH [(157.5±4.5 vs 148.1±4.6)cm,P<0.01],and target height[(154.4±4.6)cm] was,significantly excceded.The control group reached an adult heisht also significandy higher than pretreatment PAH[(154.7±5.5vs 150.3±6.0)cm,P<0.01],while target height[(155.6±4.3)cm]was just reached but not significantlyexcceded.The gain in height obtained,calculated between pretreatment PAH and final heisat,(9.4±4.9)cm in rhGH-combined group was much more than that(4.3±4.2)cm in the control group(P<0.01).Conclusion RhGH may accelerate the linear growth and improve adult height of GnRHa-treated ICPP girls.
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Gonadotropin releasing hormone agonists(GnRHa)are the relatively safe drugs widely used in clinic to treat precocious puberty.After therapy withdrawal,the patients would have normal menstrual onset,gestation and fertility.GnRHa didn't degrade uterus volume of post puberty.After cessation of GnRHa,luteinizing hormone,follicle stimulating hormone and sex hormone levels would return to those before therapy,or even exceed them.Some researches suggested that gonadotropin releasing hormone analogue might increase the risk of androgen excess and polycystic ovary syndrome.The researches apply no sufficient evidences to show that GnRHa had significant and irreversible negative influences on bone mineral density.GnRHa might have the side effect of increasing body mass index(BMI).However,researches also showed that GnRHa was helpful to decrease BMI,or not to increase it.
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Objective To study the clinical effect of gonadotropin releasing hormone-analogue (GnRH-a) and marvelon in the treatment of ovarian endometriesis after laparoscopy.Method The postoperative women with ovarian endometriosis were divided into three groups:19 treated with GnRH-a and marvelon(greup A),20 treated with GnRH-a(group B),20 without endocrinal therapy(group C).The symptoms scores,the recurrence and side effects were compared.ResultsThree years after laparescopy,the recurrent rate and symptoms scores in group C was the highest (P＜0.05),the recurrent cyst size [(12 + 1)mm] and symptoms scores [(1.2 + 0.9)scores] in group A was the lowest among three groups.Conclusions Marvelon and GnRH-a can be used in the treatment of ovarian endometriesis after laparoseopy.The effect of marvelon combined with GnRH-a is prior to GnRH-a.
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PURPOSE: Many recent studies have been performed to improve adult height in short normal girls with early puberty by arresting rapid pubertal progression. We evaluated the effect of combined therapy with growth hormone (GH) and gonadotropin releasing hormone agonist (GnRHa) on predicted adult height in girls with early puberty, comparing them with a group treated with GnRHa alone. METHODS: Twenty eight girls with early puberty were classified into two groups and treated for an average 18 months. Group I of 18 girls was treated with GnRHa alone (leuprolide acetate; dosage: 30-90 mcg/kg, s.c. every 28 days) and group II of 10 girls was treated in combination with GH (dosage: 0.1 IU/kg, s.c. 5-7 days/week). Two groups were compared in terms of bone age, height, sexual maturity, and predicted adult height at the start and after the treatment. RESULTS: Two groups were not significantly different from each other in chronologic age, bone age, weight, target height, and sexual maturity before and after treatment. After treatment, group I showed predicted adult height (157.1+/-6.2 cm) which was comparable to target height (157.1+/-3.7 cm) and was not significantly higher than predicted adult height before treatment (156.0+/-6.5). On the contrary, group II showed predicted adult height (158.5+/-4.6 cm) which was comparable to target height (156.2+/-3.6 cm), but significantly higher than predicted adult height before treatment (154.2+/-7.4 cm) (P<0.05). CONCLUSIONS: GH and GnRHa combination treatment is more effective than GnRHa treatment alone to improve predicted adult height in girls with early puberty.
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Adolescent , Adult , Female , Humans , Gonadotropin-Releasing Hormone , Gonadotropins , Growth Hormone , PubertyABSTRACT
3-8 years old group(group C2) with 50 cases] were detected.A gonadotropin releasing hormone analogue(GnRHa) stimulation test was performed in 140 girls with IPT.The 140 girls were divided into 3 groups:IPT group,CPP group,and peripheral precocious puberty group(PPP group).Kruskal-Wallis and Mann-Whitneg tests were performed on the data between every groups.Results For basal LH levels,there were significant diffe-rences between IPT1 group and group C1,among IPT2 group,CPP group and group C2(Pa0.05).For peak LH/FSH ratios,there was significant difference between IPT2 group and CPP group(P
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PURPOSE: The recent results observed in precocious puberty and the hope that interrupting puberty might increase adult height have led to an attempt to use GnRH agonist(GnRHa) in children with premature puberty and a poor growth prognosis. We aimed to analyze the growth promoting effect of GnRHa in girls with early puberty and low predicted adult height(PAH). METHODS: Thirty six girls were recruited. They were grouped according to the GnRHa treatment period(group 1>6 mo, n=18; group 2<6 mo, n=18). The following variables were analyzed before and after GnRHa treatment:chronological age(CA), bone age(BA), delta age(CA-BA), height, target height (TH), PAH, serum IGF-1, IGFBP-3. RESULTS: Duration of the GnRHa treatment was 0.89+/-0.81 yr(1.37+/-0.92 yr in group 1, and 0.41+/-0.08 yr in group 2). Before treatment, none of the variables were different between the two groups. There were no differences in the following variables the between two groups at the end of treatment:CA, BA, delta age, PAH, serum IGF-1, IGFBP-3. But, growth velocity(GV) and PAH increment during treatment were significantly reduced in group 1. Compared with initial PAH, PAH at the end of treatment was significantly increased(3.7+/-3.2 cm). The last serum levels of IGF-1 and IGFBP-3 were lower than those before treatment. CONCLUSION: Even though last PAH didn't approach TH, short term GnRHa administration in early puberty with low predicted PAH was somewhat effective. But, GnRHa administration suppressed the growth hormone-IGF-1 axis. Therefore, it is recommended that growth hormone(GH) should be used in combination with GnRHa.
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Adolescent , Adult , Child , Female , Humans , Axis, Cervical Vertebra , Gonadotropin-Releasing Hormone , Growth Hormone , Hope , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor I , Prognosis , Puberty , Puberty, PrecociousABSTRACT
AIM:To investigate whether gonadotropin-releasing hormone analogue(GnRHa)affect the sensitivity of breast cancer cells to 5-FU and epirubicin in vitro.METHODS:Two breast cancer cell lines(MCF-7 and MDA-MB-231)were treated with different concentrations of GnRH analogue,triptorelin acetate,or with a GnRHa+5-FU or GnRHa+epirubicin.The cellular growth profiles were determined by CCK-8.The mRNA levels of GnRH receptor,PCNA and MDR1 were measured by RT-PCR.RESULTS:Both cell lines had positive GnRH receptor mRNA expression detected by RT-PCR.GnRHa did not suppress cell growth after GnRHa exposure.IC50 of 5-FU and epirubicin was not changed in the presence of GnRHa.Suppression of cell growth by the exposure to 5-FU and epirubicin was not changed in the presence of GnRHa.GnRHa treatment up-regulated PCNA mRNA expression in MDA-MB-231 cells but not in MCF-7 cells.The expression of MDR1 mRNA was down-regulated by GnRHa in MCF-7 cell lines.No MDR1 mRNA expression in MDA-MB-231 cells was observed.CONCLUSION:The present data suggest that GnRH analogue(triptorelin acetate)does not affect the sensitivity of breast cancer cell lines MCF-7 and MDA-MB-231 to 5-FU and epirubicin.GnRHa may decrease the drug resistance by down-regulating MDR1 mRNA expression.