GnRH agonist

gnrh 激动剂
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    文章类型: Journal Article
    甲状腺炎可能是由戈舍瑞林(促性腺激素释放激素的长效类似物)引起的,用于治疗子宫内膜异位症的疼痛和出血。戈舍瑞林诱发的甲状腺炎有可能影响甲状腺功能,因此可能导致高tech酸钠Tc-99m甲状腺扫描的摄取不良。
    本病例报告重点介绍了一例罕见的中年妇女,有症状的毒性甲状腺肿,其高科技酸钠Tc-99m甲状腺扫描摄取被戈舍瑞林治疗抑制。
    照顾戈舍瑞林患者的医务人员需要意识到其影响甲状腺功能的可能性。
    UNASSIGNED: Thyroiditis may be induced by goserelin (a long acting analogue of gonadotropin - releasing hormone) prescribed for the treatment of pain and bleeding of endometriosis. Goserelin induced thyroiditis has a possibility of affecting thyroid function and hence may cause poor uptake on sodium pertechnetate Tc-99m thyroid scan.
    UNASSIGNED: This case report highlights a rare instance of a middle-aged woman with symptomatic toxic goitre whose sodium pertechnetate Tc-99m thyroid scan uptake was inhibited by goserelin therapy.
    UNASSIGNED: Medical personnel caring for patients on goserelin need to be aware of the possibility of it affecting thyroid function.
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  • 文章类型: Case Reports
    非梗阻性无精子症(NOA)是男性因素不育的最严重形式。它由原发性或继发性睾丸衰竭引起。这里,我们报告了两名由于成熟停滞和血清FSH升高而患有NOA的患者的病例,用GnRH激动剂和促性腺激素治疗。两名NOA患者接受了药物治疗,包括使用GnRH激动剂进行垂体脱敏和使用垂体促性腺激素进行睾丸刺激。睾丸刺激在开始GnRH激动剂治疗后一个月开始。女性伴侣接受控制性卵巢刺激(COS),然后进行卵胞浆内单精子注射(ICSI)。在循环的第三天,给药每日剂量的促性腺激素。当可见至少一个卵泡≥14毫米时,使用GnRH拮抗剂ganirelix进行垂体阻断。当三个或更多卵泡达到平均直径≥17mm时,给予醋酸曲普瑞林以触发最终的卵泡成熟。35小时后进行卵母细胞取回。治疗后,男性伴侣血液中的FSH水平,LH,降低和总睾酮增加。在两种情况下,收集精液后都观察到精子。COS之后,检索卵母细胞并进行ICSI。对胚胎进行活检以进行植入前遗传学检测(PGT),并将那些被认为是整倍体的胚胎转移,从而导致植入阳性。正在怀孕,这两种情况下的生活分娩。在本报告中,我们提出了一种成功的高促性腺功能减退症AOA男性策略,作为手术睾丸精子回收的替代方法。然而,需要前瞻性随机试验来证实我们的发现.
    Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility. It results form from either primary or secondary testicular failure. Here, we report cases of two patients with NOA due to maturation arrest and increased serum FSH, treated with GnRH agonist and gonadotrophins. The two NOA patients underwent a pharmacological treatment consisting of pituitary desensibilization using a GnRH agonist and testicular stimulation using menotropin. Testicular stimulation started one month after the beginning of GnRH agonist treatment. The female partner underwent controlled ovarian stimulation (COS) followed by intracytoplasmic sperm injection (ICSI). On the third day of the cycle, menotropin daily doses was administered. When at least one follicle ≥14 mm was visualized, pituitary blockage was performed using GnRH antagonist ganirelix. When three or more follicles attained a mean diameter of ≥17 mm, triptorelin acetate was administered to trigger final follicular maturation. Oocyte retrieval was performed 35 hours later. After treatment, male partner blood levels of the FSH, LH, decreased and total testosterone were increased. Spermatozoa was observed after semen collection in both cases. After COS, oocytes were retrieved and ICSI was performed. Embryos were biopsied for preimplantation genetic testing (PGT) and those considered euploidy were transferred resulting in positive implantation, ongoing pregnancy, and livebirth on both cases. In this report we present a successful strategy for hypergonadotropic hypogonadism AOA men, as an alternative approach to the surgical testicular sperm recovery. Nevertheless, prospective randomized trials are needed to confirm our findings.
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  • 文章类型: Journal Article
    背景:口服促性腺激素释放激素拮抗剂relugolix,暂时停止月经,用于治疗大量月经出血,骨盆压力,子宫肌瘤女性的腰背痛。治疗还可以帮助女性从低血红蛋白水平中恢复,并可能缩小肌瘤。然而,腹腔镜子宫肌瘤切除术前使用relugolix的证据有限.然而,治疗可以减少手术间失血,降低术后贫血的风险,缩短手术时间。因此,我们的目的是测试12周术前治疗是否使用relugolix(口服40毫克,每天一次)与亮丙瑞林(每4周注射一次)相似或不差于亮丙瑞林(每4周注射一次),以减少术中失血。
    方法:术前用药的有效性和安全性将在多中心进行研究,随机化,开放标签,平行组,非劣效性试验招募年龄≥20岁的绝经前妇女,诊断为子宫肌瘤,并计划进行腹腔镜子宫肌瘤切除术。参与者(n=80)将在参与机构的临床环境中招募。在1:1分配中使用随机化的最小化方法(预定义的因素:是否存在≥9cm的肌瘤以及国际妇产科联合会[FIGO]1-5型肌瘤)。Relugolix是一种40毫克的口服片剂,每天饭前服用一次,12周,直到手术前一天。亮丙瑞林是1.88毫克,或3.75毫克皮下注射,在手术前患者访视期间间隔3个4周给予。对于术中出血的主要结果测量,从体腔收集血流,手术海绵,和收集袋,以毫升为单位。次要结果指标是血红蛋白水平,肌瘤大小,其他手术结果,和生活质量问卷回答(KuppermanKonenkiShogai指数和子宫肌瘤症状-生活质量)。
    结论:将在临床环境中收集使用口服促性腺激素释放激素拮抗剂的预治疗以减少腹腔镜子宫肌瘤切除术妇女的术中出血的真实世界证据。
    背景:jRCTs031210564于2022年1月19日在日本临床试验注册中心注册(https://jrct。尼夫.走吧。jp)。
    BACKGROUND: The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss.
    METHODS: Efficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants (n = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1-5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms-Quality of Life).
    CONCLUSIONS: Real-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy.
    BACKGROUND: jRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ).
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  • 文章类型: Journal Article
    这项前瞻性研究旨在测试卵泡GnRH激动剂激发试验(FACT)预测对GnRH激动剂触发的次优反应的能力,非医疗卵母细胞冷冻保存计划中排卵触发后LH水平评估。该研究包括91名接受非医学生育能力保存的妇女。在月经周期的第二天,进行了血液检查(基础雌二醇,基础FSH,基础LH,进行孕酮)和超声(US)。那天晚上,指示这些妇女注射0.2mgGnRH激动剂(FACT),并在第二天早上10-12小时后进行反复血液检查,其次是灵活的拮抗剂方案。将排卵触发后早晨的LH水平与FACTLH水平进行比较。结果表明,激动剂排卵触发后的LH水平低于15IU/L发生在1.09%的周期中,由FACT预测,r=0.57,p<0.001。ROC分析表明,FACTLH>42.70IU/L可以预测触发后LH超过30IU/L,灵敏度为75%,特异性为70%,AUC=0.81。触发后的LH水平也显示出与基础FSH(r=0.35,p=0.002)和基础LH(r=0.54,p<0.001)的显着正相关。排卵触发后LH水平与卵母细胞总数或成熟率无关。与冷冻卵母细胞数量的最强相关性是激动剂触发后的孕酮水平(r=0.746,p<0.001)。我们得出结论,对激动剂触发剂的反应欠佳,根据触发后LH水平评估,这是一种罕见事件.FACT可以作为辅助预触发因素,用于预测激动剂排卵触发后LH水平升高的周期内工具。未来的研究应集中在优化激动剂触发剂的疗效评估和预测上。尤其是在高反应者中。
    This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10-12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders.
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  • 文章类型: Journal Article
    促黄体生成素(LH)存在于整个自然卵泡期。然而,关于IVF中卵巢刺激期间是否需要LH的争论仍未解决.这篇评论着眼于这场辩论的演变,提到房间里被制药行业忽视的三只大象,专业组织,和临床医生一样:1。长激动剂和拮抗剂方案之间的不同内分泌学。2.两种市售最广泛的拮抗剂制剂的固定剂量,即cetrorelix和ganirelix.3.事实上,该领域的大多数研究都使用基于人口的标准,忽略内分泌参数。LH受体基因的个体遗传学也可能有助于在刺激期间个性化LH需求;然而,关于这种方法,陪审团仍然没有意见。结论:个体内分泌和遗传学参数可能对卵巢刺激期间补充LH的问题有意义。
    Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: 1. The different endocrinology between the long agonist and the antagonist protocols. 2. The fixed dose of the two most widely commercially available antagonist preparations, namely cetrorelix and ganirelix. 3. The fact that most research in this area uses population-based criteria, ignoring endocrine parameters. Individual genetics of the LH receptor gene may also serve to individualize LH needs during stimulation; however, the jury is still out regarding this approach. CONCLUSIONS: Individual endocrine and genetics parameters may shed meaningful light on the question of LH supplemental during ovarian stimulation.
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  • 文章类型: Randomized Controlled Trial
    目的:比较促性腺激素释放激素(GnRH)拮抗剂单药治疗与雄激素阻断(CAB)联合GnRH激动剂和比卡鲁胺治疗晚期激素敏感型前列腺癌(HSPC)的有效性和安全性。
    方法:本研究按照KYUCOG-1401试验(UMIN000014243)进行,纳入200名患者,随机分为A组(GnRH拮抗剂单药治疗,然后加用比卡鲁胺)或B组(GnRH激动剂和比卡鲁胺的CAB)。主要终点是PSA无进展生存期。次要终点是CAB治疗失败的时间,放射学无进展生存期,总生存率,血清参数的变化,包括PSA,荷尔蒙,骨骼和脂质代谢标记物,和不良事件。
    结果:B组PSA无进展生存期显著延长(风险比[HR],95%置信区间[CI];1.40,1.01-1.95,p=0.041)。A组CAB治疗失败的时间稍长(HR,95%CI;0.80,0.59-1.08,p=0.146)。在放射学无进展生存期或总生存期方面没有观察到显著差异。在A组中,血清睾酮未达到去势水平的患者百分比在60周时较高(p=0.046)。两组之间的骨代谢或脂质标志物的血清水平没有显着差异。A组的注射部位反应更为频繁。
    结论:本研究结果支持使用GnRH激动剂和比卡鲁胺的CAB治疗晚期HSPC比GnRH拮抗剂单一疗法更有效。
    OBJECTIVE: To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC).
    METHODS: The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events.
    RESULTS: PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01-1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59-1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A.
    CONCLUSIONS: The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    GnRH analogues were widely used for controlld ovary stimulation, but their effects on oocyte quality remain contradictory. This study aimed to explore the influence of GnRH analogues on oocyte quality in mice. A total of 120 mice were randomly assigned to four groups:(i)GnRH-a+PMSG group; (ii) GnRH-ant+PMSG group; (iii) PMSG group; (iv) Control group. Ovaries were collected for quantitative real-time polymerase chain reaction (qRT-PCR) to assess GDF9 and BMP15 mRNA expression, and protein expression were evaluated by western blotting. Moreover, embryo developmental progress in vitro and implantation rate in vivo were recorded. Compared with control group, both GDF9 mRNA and protein expressions were strengthened in PMSG group, but reduced in the presence of GnRH-a or GnRH-ant. The GnRH-a group exhibited decreased BMP15 mRNA expression compared to PMSG group, while the GnRH-ant group did not show the same pattern. BMP15 protein expression were not statisticlly different among the four groups. Notably, there was no statistically difference in the expression of these two factors between GnRH-a and GnRH-ant groups. The percentage of zygotes progressing to the 2-cell stage and percentage of 2-cell advancing to the blastocyst stage were similar in the PMSG group and control group. However, both the GnRH-a and GnRH-ant groups showed decreased embryos development rates compared to other two groups. The embryonic implantation rate in control group (53.3%) was higher than that in the GnRH-a and GnRH-ant groups (33.3% and 30.8%, P<0.05). The difference between the PMSG (45.0%) and GnRHa group was statistically significant (P value of 0.023), but not between the PMSG and GnRH-ant group (P value of 0.486). No statistical difference was confirmed between GnRH-a and GnRH-ant groups. Our findings shed light on the safety of GnRH analogues in ovary stimulation, and highlight the need for further research to establish optimal and effective controlled ovary stimulation protocol.
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  • 文章类型: Journal Article
    目的:本研究旨在比较单用促性腺激素释放激素激动剂(GnRHa)触发剂与包含GnRHa和低剂量人绒毛膜促性腺激素(hCG)的双重触发剂对多囊卵巢综合征(PCOS)患者生殖结局的影响。
    方法:本回顾性队列研究共纳入615个周期。进行倾向评分匹配(PSM)以1:1的比例控制GnRHa触发组(0.2mgGnRHa)和双触发组(0.2mgGnRHa加1000/2000IUhCG)之间的潜在混杂因素。应用多变量逻辑回归估计触发方法与生殖结局之间的关联。
    结果:PSM后,双重触发的患者(n=176)获得了更多的卵母细胞,成熟卵母细胞,和2PN胚胎与单独的GnRHa触发相比。然而,卵母细胞成熟率,正常受精率,而冷冻胚胎两组间差异无统计学意义。卵巢过度刺激综合征(OHSS)的发病率(14.8%vs.2.8%,P<0.001)和中度/重度OHSS(11.4%vs.1.7%,P<0.001)在双触发组中明显高于GnRHa单独组。Logistic回归分析显示,OHSS双触发因素的校正比值比为5.971(95%置信区间2.201~16.198,P<0.001)。两组妊娠结局和单胎结局具有可比性(P>0.05)。
    结论:对于采用全部冻结策略的PCOS女性,单独触发GnRHa可降低OHSS的风险而不损害卵母细胞成熟,并获得满意的妊娠结局。
    This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy.
    A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2 mg GnRHa) and dual-trigger group (0.2 mg GnRHa plus 1000/2000 IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes.
    After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05).
    For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.
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  • 文章类型: Journal Article
    本研究旨在探讨促性腺激素释放激素激动剂(GnRHa)对青春期早快女孩最终成年身高(FAH)的影响。
    通过回顾2010年1月1日至2020年12月31日在MacKay儿童医院的儿科内分泌科诊所的医疗记录数据,进行了一项回顾性研究。治疗组包括109名患者,每月接受3.75mg,持续至少1年,而对照组由95名未接受治疗的女孩组成。
    治疗组在纳入时明显年龄较大(实际年龄(CA1),治疗vs.control,8.7vs.8.4年,p<0.001),骨龄更高(BA)(BA1,11.5vs.10.8年,p<0.001),BA1-CA1(2.7vs.2.2年,p<0.001),和较短的预测成人身高(PAH1)(153.3vs.157.1cm,p=0.005),显着低于其目标高度(Tht)(PAH1-Tht,-3.9vs.-1.3厘米,p=0.039)。GnRHa和对照组的FAHs相似(157.0vs.156.7cm,p=0.357),并且与他们的Tht没有显着差异(FAH与在GnRHa组中,157.0vs.157.0cm;对照组,156.7vs.157.0厘米)。在亚组分析中,在PAH1小于153cm和Tht的患者中,GnRHa治疗后FAH显着升高(154.0vs.152.0厘米,p=0.041),和那些CA1在8到9岁之间的人(158.0vs.155.4厘米,p=0.004)。我们将满意的FAH结果定义为FAH-PAH1≥5cm,重要因素是GnRHa治疗,PAH1比他们的短,年龄小于9岁,第一年的增长速度更快。
    GnRHa可有效恢复一些青春期早快的女孩的Tht,尤其是在PAH较差(PAH低于153厘米且短于目标高度)的人群中。开始治疗时年龄较小,治疗过程中生长速度较快,身高增长较好。
    This study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty.
    A retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children\'s Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment.
    The treatment group was significantly older at the time of inclusion(chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht)(PAH1-Tht, -3.9 vs. -1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH-PAH1≥5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year.
    GnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain.
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