• Korean Journal of Veterinary Research
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• v.39 no.2
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• pp.276-286
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• 1999

In the present study, to understand how gonadotropin-releasing hormone (GnRH) affects ovarian functions in superovulated rats, we examined the effects of GnRH agonist on the ovulatory response, the morphological normality and nuclear maturation of ovulated oocytes, the ovarian weight, the ovarian histology, and the circulating steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in immature rats pretreated with 30IU pregnant mare serum gonadotropin (PMSG) and supplemented with 10IU human chorionic gonadotropin(hCG). GnRH agonist was intravenously injected via jugular vein catheter every 20min for 4hrs in early follicular phase (from 6hr after PMSG) of superovulated rats. In addition, GnRH antagonist, Antide, was intravenously injected in combination with GnRH agonist to verify the effects of GnRH agonist on ovarian functions. All animals were sacrificed at 72hr after PMSG administration. The administration with GnRH agonist in early follicular phase of superovulated rats caused inhibition of ovulatory response, increased the proportion of abnormal appearing oocytes(especially, in the rats of the group treated with 500ng GnRH agonist), decreased ovarian weight and promote follicular atresia, compared to those from the rats of control regimen that were not treated with GnRH agonist. In addition, the treatment with GnRH agonist in the superovulated rat distinctly decreased serum steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in preovulatory phase. On the other hand, the inhibitory effects of GnRH agonist treatment in superovulation-pretreated rats on ovarian functions were totally reversed by the combination with GnRH antagonist, Antide. The nuclear maturation of oocytes recovered from the oviducts in immature rats treated with GnRH agonist and/or GnRH antagonist was characterized by prematurity and asynchronization in early follicular phase, which was similar to control group. The overall results of this study indicate that GnRH agonist disturbs directly ovarian function in early follicular phase of superovulated immature rats in terms of ovulatory response and morphological normality of ovulated oocytes. This concept has been further evidenced by the findings of a great decrease in ovarian weight, a marked increase in follicular and a distinct decrease circulating steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in GnRH agonist treatment regimen in early follicular phase.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.1
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• pp.11-26
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• 2021

Advances in anticancer treatments have resulted in increasing survival rates among cancer patients. Accordingly, the quality of life after treatment, particularly the preservation of fertility, has gradually emerged as an essential consideration. Cryopreservation of embryos or unfertilized oocytes has been considered as the standard method of fertility preservation among young women facing gonadotoxic chemotherapy. Other methods, including ovarian suppression and ovarian tissue cryopreservation, have been considered experimental. Recent large-scale randomized controlled trials have demonstrated that temporary ovarian suppression using gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy is beneficial for preventing chemotherapy-induced premature ovarian insufficiency in breast cancer patients. It should also be emphasized that GnRHa use during chemotherapy does not replace established fertility preservation methods. All young women facing gonadotoxic chemotherapy should be counseled about and offered various options for fertility preservation, including both GnRHa use and cryopreservation of embryos, oocytes, and/or ovarian tissue.

• Molecules and Cells
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• v.25 no.1
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• pp.91-98
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• 2008

The Glu/$Asp^{7.32}$ residue in extracellular loop 3 of the mammalian type-I gonadotropin-releasing hormone receptor (GnRHR) interacts with $Arg^8$ of GnRH-I, conferring preferential ligand selectivity for GnRH-I over GnRH-II. Previously, we demonstrated that the residues (Ser and Pro) flanking Glu/$Asp^{7.32}$ also play a role in the differential agonist selectivity of mammalian and non-mammalian GnRHRs. In this study, we examined the differential antagonist selectivity of wild type and mutant GnRHRs in which the Ser and Pro residues were changed. Cetrorelix, a GnRH-I antagonist, and Trptorelix-2, a GnRH-II antagonist, exhibited high selectivity for mammalian type-I and non-mammalian GnRHRs, respectively. The inhibitory activities of the antagonists were dependent on agonist concentration and subtype. Rat GnRHR in which the Ser-Glu-Pro (SEP) motif was changed to Pro-Glu-Val (PEV) or Pro-Glu-Ser (PES) had increased sensitivity to Trptorelix-2 but decreased sensitivity to Cetrorelix. Mutant bullfrog GnRHR-1 with the SEP motif had the reverse antagonist selectivity, with reduced sensitivity to Trptorelix-2 but increased sensitivity to Cetrorelix. These findings indicate that the residues flanking $Glu^{7.32}$ are important for antagonist as well as agonist selectivity.

• Journal of Breast Disease
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• v.6 no.2
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• pp.46-51
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• 2018

Purpose: Endocrine therapy is the preferred treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated the efficacy of combined aromatase inhibitor (AI) and luteinizing hormone-releasing hormone (LHRH) agonist in premenopausal patients with HR-positive MBC. Methods: We retrospectively analyzed the medical records of 21 HR-positive premenopausal MBC patients treated with combined AI and LHRH agonist therapy. Results: The median follow-up period was 32.9 months. The overall response rate was 47.6%, with three complete responses (14.3%) and seven partial responses (33.3%). Nine patients (42.9%) achieved stable disease lasting more than 6 months; thus, the clinical benefit rate was 90.4%. The median time to progression was 45.4 months. No patients experienced grade 3 or 4 toxicity. Conclusion: Combined AI and LHRH agonist treatment safely and effectively induced remission or prolonged disease stabilization, suggesting that this could be a promising treatment option for HR-positive premenopausal patients with MBC.

• Clinical and Experimental Reproductive Medicine
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• v.18 no.2
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• pp.201-208
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• 1991

Recently the application of gonadotropin-releasing hormone (GnRH) agonist to superovulation in previous poor responders has resulted in the improved outcomes after in vitro fertilization (IVF) outcome. However, poor responders with poor estradiol $(E_2)$ rise or single dominant follicle are a particularly challenging group. Recent reports have also shown that patients with higher basal serum follicle stimulating hormone (FSH) level, result in poorer ovarian response and lower pregnancy rate. Analysis of the differences of superovulation outcomes according to the different protocols of GnRH agonist, long (L, n = 18) and short (S, n = 16) protocols, in patients with high basal FSH levels (>20mIU/ml) were undertaken at Seoul National University Hospital from June to October 1990. The administration of GnRH agonist was begun on day 21 of the cycle in long protocol, and on day 2 in short protocol. Ages of patients and husbands, basal FSH and luteinizing hormone (LH) levels and FSH/LH ratio did not differ significantly. Types and causes of infertility were evenly distributed. Whereas the duration of stimulation and the amounts of gonadotropins administered were significantly reduced in short protocol, the numbers of oocytes retrieved and cleaved, the cleavage rate and the number of embryos transferred were higher in long protocol without statistical signifieance. The pregnancy rate per ET was 16.7% (2/12) in short protocol, and 17.6% (3/17) in long protocol. These data suggest that both protocols result in the similar superovulation outcomes in patients with higher basal serum FSH levels.

• Clinical and Experimental Reproductive Medicine
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• v.18 no.2
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• pp.189-196
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• 1991

Long-term administration of luteinizing hormone-releasing hormone(LHRH) agonists, through a process of pituitary desensitization and down-regulation of receptors, inhibits the secretion of gonadotropin and sex-steroids and induces a reversible suppression of gonadal activity. This approach can be used as an effective endocrine therapy for some hormone-dependent tumors. We have used D-Trp6-LHRH, a long acting LHRH agonist, for the treatment of eleven patients with uterine leiomyomas, thereafter myomectomy was performed in seven cases and observed the ultrastructural changes of leiomyoma with an electron microscope. The use of LHRH agonist may be effective in reducing the size of a myoma considerably by primarily inducing medical hypophysectomy and would allow easier surgical removal. Electron microscopic findings of myoma cells after the use of LHRH agonist included the following: loss of cristae and swelling nuclear chromatin, perinuclear vacuolation in cytoplasm. Bone mineral density was slightly decreased, however, the difference was not statistically significant.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.3
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• pp.169-173
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• 2016

Objective: To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozenthawed embryo transfer (FET) cycles following GnRH agonist treatment. Methods: This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. Results: GnRH agonist pretreatment increased the stimulation duration ($11.5{\pm}2.1days$ vs. $9.9{\pm}2.0days$) and total dose of gonadotropin ($3,421{\pm}1,141IU$ vs. $2,588{\pm}1,192IU$), which resulted in a significantly higher number of retrieved oocytes ($10.0{\pm}8.2$ vs. $7.9{\pm}6.8$, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes ($14.3{\pm}9.2$ vs. $10.0{\pm}8.2$, p=0.022) with a lower dose of gonadotropin ($2,974{\pm}1,112IU$ vs. $3,421{\pm}1,141IU$, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. Conclusion: FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further largescale prospective studies are required to confirm this result.

• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.4
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• pp.188-196
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• 2018

Objectives: This study is to report the clinical effectiveness of the complex Korean medicine therapy on a postoperative endometriosis patient's hypoestrogenic side effects who is treated with GnRH-agonist injection. Methods: The patient in this case was diagnosed with endometriosis and has been treated with GnRH-a injection after laparoscopic operation. The patient complained hot flash and sweating mainly after GnRH-a treatment. The patient received complex Korean medicine therapy during 10 days admission period. The clinical effects were evaluated through KI (Kupperman's Index) and SF-36 (36 item Short Form Health Survey). Results: After the complex Korean medicine therapy, the various clinical symptoms including hot flash and sweating were improved. Also, the quality of life was enhanced. Conclusions: This case report shows that the complex Korean medicine therapy was effective for treating hypoestrogenic side effects occurred after GnRH-a treatment in postoperative endometriosis patient.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.239-244
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• 2010

Objective: The objective of this retrospective study was to compare the in vitro fertilization (IVF) outcomes of gonadotropinreleasing hormone (GnRH) agonist and GnRH antagonist protocols in poor responders. Methods: A total of 172 cycles in subjects with less than 5 oocytes retrieved treated with either GnRH agonist long protocols or antagonist protocols were included. The outcome variables such as numbers of growing follicles and retrieved oocytes, and the fertilization rate were evaluated as the main outcome measures. Results: There was no difference in regard to the numbers of growing follicles and oocytes, and fertilization rate between the two groups. $E_2$ level on Day 7/8, mean gonadotropin dose, and the days of stimulation were shown to be statistically different (p<0.01, respectively). Conclusion: Considering that similar results were observed with less time and gonadotropin dose, GnRH antagonist protocol may be considered as a preferable choice over GnRH agonist protocols in poor responders.

• Clinical and Experimental Pediatrics
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• v.60 no.12
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• pp.395-402
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• 2017

Purpose: The potential effect of gonadotropin-releasing hormone agonist (GnRHa) treatment on the weight of girls with central precocious puberty (CPP) remains a controversy. We investigated anthropometric changes during and after GnRHa treatment among girls with CPP. Methods: This retrospective study evaluated data from 127 girls with CPP who received GnRHa treatment for ${\geq}2years$. Height, weight, and body mass index (BMI) values were compared at the baseline (visit 1), after 1 year of GnRHa treatment (visit 2), the end of GnRHa treatment (visit 3), and 6-12 months after GnRHa discontinuation (visit 4). Results: The height z score for chronological age (CA) increased continuously between visit 1 and visit 4. No significant differences were observed in BMI z score for CA between visits 1 and 4. However, an increasing trend in the BMI z score for bone age (BA) was observed between visits 1 and 4. The numbers of participants who were of normal weight, overweight, and obese were 97, 22, and 8, respectively, at visit 1, compared to 100, 16, and 11, respectively, at visit 4 (P=0.48). Conclusion: Among girls with CPP, the overall BMI z score for CA did not change significantly during or after GnRHa treatment discontinuation, regardless of their BMI status at visit 1. However, the BMI z score for BA showed an increasing trend during GnRHa treatment and a decreasing trend after discontinuation. Therefore, long-term follow-up of BMI changes among girls with CPP is required until they attain adult height.