Effect of dietary with Zhibai dihuang pills and gonadotropinreleasing-hormone-analogue on girls with precocious and rapidly progressive puberty

BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy

BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy(NAC),and the oncologic efficacy of gonadotropin-releasing hormone(GnRH)agonists.METHODS This retrospective study involved a prospectively enrolled cohort.We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017.Among patients with HR-positive and human epidermal grow factor 2(HER2)-negative breast cancer,we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years.RESULTS Among 431 patients with NAC and HR-positive/HER2-negative breast cancer,78 were 35 years old or younger,and 353 patients were older than 35 years.The median follow-up was 71.0 months.There was no statistically significant difference in disease free survival(DFS,P=0.565)and overall survival(P=0.820)between the patients equal to or younger than 35 years and the patients older than 35 years.The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group(52.4%vs 11.2%,P<0.001).Interestingly,for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years,patients treated with the GnRH agonist had better DFS(P=0.037).CONCLUSION Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins:Two case reports

BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.

Influence of Different Gonadotropin-releasing Hormone Agonist Administration Methods on Pregnancy Outcomes of Patients Undergoing In-vitro Fertilization-embryo Transfer

This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (w=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), folliclestimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, M II rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the shortacting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<O.Ol). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.

Associations of Gonadotropin-Releasing Hormone Receptor (GnRHR) and Neuropeptide Y(NPY) Genes’Polymorphisms with Egg-Laying Traits in Wenchang Chicken

Single nucleotide polymorphisms （SNP） of chicken gonadotropin-releasing hormone receptor （GnRHR） and neuropeptide Y （NPY） were selected to identify the genotypes of Wenchang （Chinese indigenous breed） chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production （NE）, average days of continual laying （ADCL）, and number of double-yolked eggs （DYE） traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 （Bpu1102 Ⅰ A） and 0.31 （Bpu1102 Ⅰ a） and for NPY 0.46 （Dra Ⅰ B） and 0.54 （Dra Ⅰ b）. Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes＇ marker were found： for GnRHR and number of eggs （dominant; t= 2.67, df= 116） and NPY and number of eggs （additive; t= 1.97, df= 116）. The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.

Artificial Cycle with or without a Depot Gonadotropin-releasing Hormone Agonist for Frozen-thawed Embryo Transfer： An Assessment of Infertility Type that Is Most Suitable

The clinical outcomes of five groups of infertility patients receiving frozen- thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone （GnRH） agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups： tubal infertility, polycystic ovary syndrome （PCOS）, endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention： group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B （control group） was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively （P〈0.05）. The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%, respectively （P〈0.05）. The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist co- treatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.

Identification and distribution of gonadotropin-releasing hormone-like peptides in the brain of horseshoe crab Tachypleus tridentatus

Gonadotropin-releasing hormone （GnRH） is a crucial peptide for the regulation of reproduction. Using immunological techniques, we investigated the presence of GnRH in horseshoe crab Tachypleus tridentatus. Octopus GnRH-like immunoreactivity, tunicate GnRH-like immunoreactivity, and lamprey GnRH-I-like immunoreactivity were detected in the neurons and fibers of the protocerebrum. However, no mammal GnRH-like immunoreactivity or lamprey GnRH-LII-like immunoreactivity was observed. Our results suggest that a GnRH-like factor, an ancient peptide, existed in the brain of T. tridentatus and may be involved in the reproductive endocrine system.

Preliminary study of gonadotropin-releasing analogue (GnRH-A) initiated gonadal development of amphioxus

Amphioxus in the seasonally regressed phase of gonadat development were used in this study. Each sample animal was injected with 40 nanogram of synthetic gonadotropin-releasing hormone analogue (GnRH-A) in distilled water every other day for up to 16 days; control animals received similar volumes of distilled wnter only. Both hormone-treated samples and control animals were examined under microscope every eight days and every twelve days. Then all the animals were killed on the 16th day. Gonads earlier development and a more advanced degree of gametogenesis are in the hormone-treated group than in the control group. Thus, GnRH-A can initiate and accelerate the gonadal development in gonadally regressed am-phioxus. GnRH-A in some form may be important in regulating the gonadal development in amphioxus as well as in vertebrates.

Morphological changes of gonadotropin-releasing hormone neurons in the rat preoptic area across puberty

Gonadotropin-releasing hormone （GnRH） neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green fluorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive maturation. There was no significant difference between male and female rats. Immunofluorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.

Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels （at 120 minutes of exposure） and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

Immunohistochemical Localization and Receptor Expression of Gonadotropin-Releasing Hormone in Pituitary of Guangxi Swamp Buffaloes

[ Objective] To locate gonadotropin-releasing hormone （GnRH） in pituitary of Guangxi swamp buffaloes and to provide a theoretical ba- sis for cloning and sequence analysis of GnRH receptor gene. [ Method] GnRH in pituitary were immunohistochemically stained by avidin biotin complex method. The GnRH expression was analyzed with image system. The GnRH receptor gene was amplified by real-time PCR. [ Result] Many GnRH positive cells were detected in pars distalis of adenohypophysis. GnRH were distributed in cytoplasm but not in nuclei. No positive sig- nal was observed in neurohypophysis. In addition, the GnRH receptor gene, 920 bp in size, was amplified. [ Conclusion] A large number of GnRH and GnRH receptor were found in pars distalis of adenohypophysis, which indicates that anterior pituitary is an important tissue for functions of hypo- thalamus-pituitary-gonadal axis and other endocrine axes.

Kisspeptin regulates gonadotropin-releasing hormone secretion in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats

Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kJsspeptJn antagonist peptJde 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.

Changes in Electrocardiogram Findings during Treatment with Gonadotropin-Releasing Hormone Agonist and Surgical Castration for Prostate Carcinoma

Purpose: To investigate electrocardiogram (ECG) changes after complete androgen blockade (CAB) achieved by either surgical or medical castration and compare the outcomes of the groups. Methods: Sixty-three consecutive men (between 58 - 86 years of age) requiring CAB for prostate cancer were enrolled in the study. Patients with diabetes mellitus, an additional malignancy, coronary heart disease, atrial fibrillation, heart failure or a medical history of cardiac event in the last 12 months were excluded from the study. Additionally, those who were taking medicine affecting heart rate were excluded. The participants were divided into two groups according to their modality of castration. The first group consisted of 35 patients who received bilateral orchiectomy plus anti-androgen medication. The second group contained 28 patients who accepted gonadotropin-releasing hormone (GnRH) plus anti-androgen therapy. After complete examinations and biochemical tests, the ECG leads of the patients were obtained conveniently. This was then repeated at three- and six-month visits. ECG findings (including heart rate, PR, QRS, QT, corrected QT (QTc) intervals and QT dispersion (QTd)) were recorded and analysed statistically. The groups were then compared in terms of pre- and post-treatment ECG outcomes. Results: Both groups revealed similarly lower heart rate and prolonged PR, QRS, QT, corrected QTc and QTd by the end of six months. By the end of three months, all variables had changed significantly in the orchiectomy group, whereas in the GnRH group, they had not. Conclusion: CAB may result in lower heart rate and prolonged QT, a condition associated with fatal cardiac arrhythmia and sudden death. Therefore, patients receiving CAB should be monitored closely for cardiac adverse effects.

中西医诊治儿童性早熟研究进展

目前,越来越多的无创诊断技术正在运用到儿童性早熟的诊断中,基因检测技术促进了该病遗传病因诊断的发展。对于该病的治疗,西医主要通过病因治疗继发性性早熟,对于特发性外周性性早熟没有特殊治疗方案,目前,中枢性性早熟治疗首选促性腺激素释放激素类似物(gonadotropin-releasing hormone agonist, GnRHa)。中医认为,性早熟病机为阴虚火旺,肝郁化火,痰湿壅滞,治以滋阴降火、疏肝解郁或燥湿化痰,可改善症状,抑制骨龄快速增长。但目前中医药治疗性早熟的临床研究证据等级不高,缺少样本量大、严格且全面的临床研究,未来可通过开展多中心的随机对照、大样本研究以验证中医药治疗性早熟的疗效。网络药理学和中药成分动物实验研究证明了中药治疗性早熟的部分机制,但中药方剂成分复杂,多通过胃肠道吸收后起效,是否可以调节肠道菌群、产生特异性菌群,该菌群是否改变了机体中某些代谢产物水平从而发挥治疗作用尚无相关研究,今后可开展更多的相关机制研究。

促性腺激素释放激素类似物对不同血清中网膜素-1水平的特发性矮小症患儿的治疗效果

目的分析促性腺激素释放激素类似物对不同血清中网膜素-1水平的特发性矮小症患儿治疗效果。方法选取2022年8月至2023年3月收治的95例特发性矮小症患儿为研究对象,以网膜素-1水平58.91 ng/mL为临界值,将网膜素-1<58.91 ng/mL的47例患儿作为低表达组,网膜素-1≥58.91 ng/mL的48例患儿作为高表达组,两组均给予促性腺激素释放激素类似物。检测对比两组体格发育指标、相关生长因子、骨代谢指标、维生素D、微量元素、甲状腺功能指标水平。结果治疗后两组患儿生长速度、身高、骨龄、预测成年身高、胰岛素样生长因子1(IGF-1)、骨密度、骨碱性磷酸酶(BALP)、Ⅰ型前胶原N端前肽(PINP)、维生素D、锌、镁、钙水平上升,且高表达组较高;人生长激素释放多肽(ghrelin)、摄食抑制因子1(nesfatin-1)、β-胶原降解产物(β-CTX)水平下降,且高表达组较低(P<0.05)。治疗后两组患儿促甲状腺激素(TSH)、游离三碘甲腺原氨酸(FT_(3))、游离甲状腺素(FT_(4))水平与治疗前相比差异无统计学意义(P>0.05),两组间比较亦差异无统计学意义(P>0.05)。结论特发性矮小症患儿采用促性腺激素释放激素类似物治疗后均取得较好效果,但网膜素-1高表达水平患儿治疗后体格发育、相关生长因子水平、骨代谢改善较为明显,维生素D、微量元素提升较为明显,且甲状腺功能无明显变化。

Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.

促性腺激素释放激素类似物治疗下丘脑错构瘤导致性早熟5例临床分析

目的 探讨儿童下丘脑错构瘤导致性早熟的临床特点和诊疗方案。方法 回顾性分析2017年5月至2021年5月广州医科大学附属妇女儿童医疗中心诊治的下丘脑错构瘤导致性早熟患儿5例。在万方数据库及PubMed数据库中检索相关文献,总结下丘脑错构瘤导致性早熟的诊治特点。结果 5例患儿初诊年龄为6月~8岁。均以性早熟为突出表现。使用促性腺激素释放激素类似物(醋酸亮丙瑞林注射液或醋酸曲普瑞林注射液)治疗。性发育均获得明显控制。5例患儿性激素水平均明显下降,骨龄均获得明显的控制。病例1月经消失,乳腺从B2期减小到B1期。病例2和病例5阴茎和睾丸没有进一步增大。病例3和病例4乳腺从B3期减小到B2期。结论 部分下丘脑错构瘤患儿主要临床表现为性早熟。若未合并癫痫等神经系统表现,可首先使用促性腺激素释放激素类似物治疗,效果良好,性早熟可得到明显控制,避免手术。

重组人生长激素联合促性腺激素释放激素类似物对青春期特发性身材矮小症男童身高及骨代谢水平的影响

目的探讨重组人生长激素(recombinant human growth hormone,rhGH)联合促性腺激素释放激素类似物(gonadotropin releasing hormone analogue,GnRHa)对青春期特发性身材矮小症(idiopathic short stature,ISS)男童身高及骨代谢水平的影响。方法选取2020年10月至2021年9月上饶市立医院收治的60例ISS男童作为研究对象,采用随机数字表法分为对照组与观察组,每组30例。对照组给予rhGH治疗,观察组给予rhGH联合GnRHa治疗。比较两组治疗前后生长参数[身高(height,Ht)、体质量(weight,Wt)、体重指数(body mass index,BMI)、生长速率(growth velocity,GV)、身高标准差积分(height standard deviation score,HtSDS)]、骨代谢指标{血清骨碱性磷酸酶(bone alkaline phosphatase,BAP)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、25-羟维生素D[25-hydroxyvitaminD,25-(OH)D]}、血脂指标[总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、动脉粥样硬化指数(atherosclerosis index,AI)]及用药安全性。结果治疗12个月后,两组Ht、BMI、HtSDS均高于治疗前,Wt大于治疗前,GV快于治疗前,且观察组Ht、BMI、HtSDS均高于对照组,Wt大于对照组,GV快于对照组,差异有统计学意义(P<0.05)。治疗12个月后,两组BAP、IGF-1、25-(OH)D水平均高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。治疗12个月后,两组HDL-C水平均高于治疗前,LDL-C水平、AI均低于治疗前,且观察组HDL-C水平高于对照组,LDL-C水平、AI均低于对照组,差异有统计学意义(P<0.05);两组组内、组间治疗前与治疗12个月后TC、TG水平比较差异无统计学意义。两组不良反应发生率比较差异无统计学意义。结论rhGH联合GnRHa治疗ISS男童可改善患儿骨代谢及血脂水平,促进其生长发育,安全性较高。