Effects Of Gonadotropin-releasing Hormone Antagonist Research Articles

Effect of Gonadotropin-Releasing Hormone Antagonist on the Expression Patterns of Insulin-Like Growth Factor 1, Androgen Receptor, and Luteinizing Hormone Receptor in an Experimental Rat Model of Functional Ovarian Cysts.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Effects of Low Luteinizing Hormone Serum Levels on Oocyte Retrieval, Fertilization Rate, and Embryo Quality during Controlled Ovarian Stimulation: Results from a Prospective Cohort Analysis

Objectives: Luteinizing hormone (LH) plays a key role in normal follicular development and oocyte maturation in controlled ovarian stimulation. LH stimulates the proliferation and differentiation of theca cells for the secretion of androgens, synergistically increasing estrogen production. This study aimed to investigate the effects of low LH concentrations on oocyte retrieval, fertilization, and embryo development in patients undergoing in vitro fertilization/intracytoplasmic sperm injection. Design: We prospectively (ClinicalTrials ID: NCT05755529) analyzed patients undergoing in vitro fertilization/intracytoplasmic sperm injection, subdividing them into three groups according to their age. Serum LH levels were evaluated on day 3, during stimulation (day 10) and before ovulation induction (day 12). Participants/Materials, Setting, Methods: Forty-three consecutive women were scheduled for IVF and received ovarian stimulation with follitropin alfa (Gonal F, Merck Serono, Germany) and ganirelix (Fyremaldel, Sun Pharma, Italy). Statistical analysis was performed with InStat 3.10, GraphPad software, San Diego, CA, USA. Normal distribution was tested by the Shapiro-Wilk test. Continuous variables were expressed as the mean and standard deviation. Categorical variables are expressed as frequencies and percentages. Results: Our data analysis suggests that serum LH levels progressively decrease during controlled ovarian stimulation, and this effect is more evident in the early phase of this procedure. From this perspective, circulating LH levels may significantly decrease during the late follicular phase due to the negative feedback of ovarian hormones from multiple follicular developments or after the suppressive effects of gonadotropin-releasing hormone antagonists. Limitations: Although our study confirms that exogenous LH can be considered a strategy in women with reduced LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome, the generalizability of the results is limited by the low number of participants enrolled. Conclusions: Exogenous LH may be considered a strategy in women with a decrease in LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome.

Chemotherapy-Related Structural Changes in Cancer: Effect of GnRH Antagonist in the Ovarian Follicles

Objectives: The adverse effect of chemotherapy on the proliferation of granulosa cells has been indicated in recent studies. Gonadotropin-releasing hormone (GnRH) antagonists exert protective effects on granulosa cells against the side effects of chemotherapy. In the present study, we aimed to evaluate the impact of cetrorelix on the proliferation of ovarian granulosa cells following administration of thiotepa in the ovaries of female mice. Materials and Methods: In this experimental study, 30 adult Balb/c female mice (5-8 weeks old, weighing 24-28 g) were divided into three groups (n=10/ each group) (Control group, T. group, and C. group). T. group received 2.5 mg/kg of thiotepa for four consecutive days. The C. group received cetrorelix (0.25 mg/kg) before and at the same time as thiotepa administration and a week after the end of thiotepa administration. Ovaries were used for quantitative and immunohistochemical studies at the end of the investigation. Results: The mean numbers of follicles such as primordial, primary, secondary, and tertiary significantly decreased in the T. group than control group (P=0.02). Cetrorelix treatment exerted a protective effect against thiotepa-induced damage by increasing the mean numbers of follicles in the ovarian cortex (P=0.04). Conclusions: As a GnRH antagonist, cetrorelix can be considered as one of the effective drugs to protect the granulosa cells against chemotherapy-induced damages in cancer disease.

The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer.

The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists. We conducted a systematic review to identify all randomized, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified 10 eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death, and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83), respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies. There is consistent but methodologically limited data to suggest that GnRH antagonists-a relatively new class of androgen deprivation therapy for prostate cancer-cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.

Effect of Gonadotropin-Releasing Hormone Antagonist on Risk of Committing Child Sexual Abuse in Men With Pedophilic Disorder

Evidence-based treatments from randomized clinical trials for pedophilic disorder are lacking. To determine whether a gonadotropin-releasing hormone antagonist reduces dynamic risk factors for committing child sexual abuse. This academically initiated, double-blind, placebo-controlled, parallel-group, phase 2 randomized clinical trial was conducted at the ANOVA center in Stockholm, Sweden, from March 1, 2016, to April 30, 2019. Individuals who contacted PrevenTell, the national telephone helpline for unwanted sexuality, were recruited. Eligible participants were men seeking help aged 18 to 66 years with a pedophilic disorder diagnosis and no contraindications to the intervention. The primary end point was assessed by intent-to-treat analysis. Randomization to receive either 2 subcutaneous injections of 120 mg of degarelix acetate or equal volume of placebo. The primary end point was the mean change between baseline and 2 weeks in the composite risk score of 5 domains of child sexual abuse ranging from 0 to 15 points; each domain could be rated from 0 to 3 points. Secondary end points included efficacy at 2 and 10 weeks as measured by the composite score, each risk domain, quality of life, self-reported effects, and adverse events. A total of 52 male participants (mean [SD] age, 36 [12] years) were randomized to receive either degarelix (n = 25; with 1 withdrawal) or placebo (n = 26). At 2 weeks, the composite risk score decreased from 7.4 to 4.4 for participants in the degarelix group and from 7.8 to 6.6 for the placebo group, a mean between-group difference of -1.8 (95% CI, -3.2 to -0.5; P = .01). A decrease was seen in the composite score at 10 weeks (-2.2 [95% CI, -3.6 to -0.7]) as well as in the domains of pedophilic disorder (2 weeks: -0.7 [95% CI, -1.4 to 0.0]; 10 weeks: -1.1 [95% CI, -1.8 to -0.4]) and sexual preoccupation (2 weeks: -0.7 [95% CI, -1.2 to -0.3]; 10 weeks: -0.8 [95% CI, -1.3 to -0.3]) in the degarelix group compared with the placebo group. No difference was seen for the domains of self-rated risk (2 weeks: -0.4 [95% CI, -0.9 to 0.1]; 10 weeks: -0.5 [95% CI, -1 to 0.0]), low empathy (2 weeks: 0.2 [95% CI, -0.3 to 0.6]; 10 weeks: 0.2 [95% CI, -0.2 to 0.6]), and impaired self-regulation (2 weeks: -0.0 [95% CI, -0.7 to 0.6]; 10 weeks: 0.1 [95% CI, -0.5 to 0.8]), or quality of life (EuroQol 5 Dimensions questionnaire index score, 2 weeks: 0.06 [95% CI, -0.00 to 0.12], and 10 weeks: 0.04; 95% CI, -0.02 to 0.10; EuroQol visual analog scale, 2 weeks: 0.6 [95% CI, -9.7 to 10.9], and 10 weeks: 4.2 [95% CI, -6.0 to 14.4]). Two hospitalizations occurred from increased suicidal ideation, and more injection site reactions (degarelix: 22 of 25 [88%]; placebo: 1 of 26 [4%]) and hepatobiliary enzyme level elevations were reported by participants who received degarelix (degarelix: 11 of 25 [44%]; placebo: 2 of 26 [8%]). Among the 26 participants randomized to receive degarelix, 20 (77%) experienced positive effects (eg, improved attitude or behavior) on sexuality and 23 (89%) reported adverse effects on the body. This trial found that degarelix reduced the risk score for committing child sexual abuse in men with pedophilic disorder 2 weeks after initial injection, suggesting use of the drug as a rapid-onset treatment option. Further studies are warranted into the effects and long-term adverse effects of hormone deficiency. EU Clinical Trials Register Identifier: 2014-000647-32.

Repeated doses of GnRH antagonist at midcycle in artificial frozen embryo transfer cycles may not affect pregnancy outcomes

No significant differences in outcomes have been found between protocols of endometrial preparation for frozen embryo transfer (FET), though gonadotropin releasing hormone (GnRH) antagonists may have detrimental effects on the endometrium. We conducted a retrospective cohort noninferiority study at a single academic center of women receiving multiple doses of mid-cycle GnRH antagonist (GAnt) to those receiving GnRH agonist (GAg) to determine if there are detrimental effects of GnRH antagonists. 1047 FET cycles were identified, detailed data was available in 840 cycles: 610 GAg and 230 GAnt cycles. Patients undergoing GAnt cycles were older (40 ± 6.6 versus 37 ± 5.1 years, p < 0.0001), more often used donor oocyte (36% versus 18.6%, p < 0.0001), and more often exhibited diminished ovarian reserve (49.1% versus 36.2%, p = 0.0009). Clinical pregnancy rates (CPRs) per transfer and implantation rates (IRs) were similar for GAnt and GAg cycles. There was a trend for higher pregnancy and IRs with GAg cycles in younger women (CPR 38.8% versus 26.7%, p = 0.16; IR 36% versus 23.3%, p = 0.07). Stratifying by diagnosis, CPR and IR were similar in GAnt and GAg cycles. A GAnt protocol of endometrial preparation for FET is not inferior to a GAg protocol regardless of patient age, use of donor oocyte, or infertility diagnosis.

Effect of GnRH antagonists on clinical pregnancy rates in ovulation induction protocols with gonadotropins and intrauterine insemination.

Intrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) was applied to selected infertile patients to determine the effect of gonadotropin-releasing hormone (GnRH) antagonists in IUI cycles, in which recombinant follicle-stimulating hormone (rFSH) had been used for COH. This study was conducted between April 1, 2009 and June 10, 2009, and involved a total of 108 patients. These patients had primary or secondary infertility, which resulted in an indication for IUI, and they each received two cycles of ovarian stimulation treatment with clomiphene citrate. The patients were randomised into two groups--patients in group A received rFSH + GnRH antagonist (n = 45), while those in group B received only rFSH (n = 63). The mean age of the patients was 31.84 ± 3.73 years and the mean body mass index (BMI) was 24.40 ± 1.88 kg/m(2). The mean age and BMI of the patients in groups A and B were not significantly different. There was no significant difference in the mean total rFSH dose administered (988.33 IU in group A and 871.83 IU in group B). When compared to group B, the mean number of follicles that were > 16 mm on the human chorionic gonadotropin (HCG) trigger day was significantly higher in group A (1.58 and 1.86, respectively; p < 0.05). When the two groups were compared, there were no statistically significant differences in the number of cancelled cycles due to premature luteinisation (none in group A vs. two in group B) and the rate of clinical pregnancy (8.9% in group A vs. 7.9% in group B). No significant improvement in the clinical pregnancy rates was observed when GnRH antagonists were used in COH + IUI cycles, despite the significant increase in the number of follicles that were > 16 mm on HCG trigger day.

Effects of gonadotropin-releasing hormone antagonists on the expression of vascular endothelial growth factor and its receptors in a rat model of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists (GnRHanta) are thought to be effective in preventing this complication, and some clinical trials have found lower incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate the effects of GnRHanta on vascular permeability and the expression of vascular endothelial growth factor (VEGF) and its receptors in a rat model of OHSS. An immature early OHSS rat model was established. Three ovarian stimulation protocols were used: pregnant mare serum gonadotropin/human chorionic gonadotropin (hCG) alone, with a GnRHanta, or with a gonadotropin-releasing hormone agonists (GnRHa). Blood and tissue samples were collected at 48 hours after hCG administration. Vascular permeability was evaluated by measuring the Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and its receptors, including flt-1 and KDR, were detected by reverse transcriptase-polymerase chain reaction and Western blotting. Treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF and its two receptors. However, GnRHanta treatment caused a greater reduction in serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa. There were no significant reductions in the expression of VEGF or its receptors in extra-ovarian tissues, including the liver, lungs and peritoneum. Our results reveal that GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries.

Effect of gonadotropin-releasing hormone antagonist on ovarian and uterine weights in immature female rats

The immature rat uterotrophic assay has been proposed as a screening test method for detecting estrogenic and antiestrogenic chemicals. Although the immature rat uterotrophic assay is advantageous because the test animals are not traumatized by the ovariectomizing process, the effect of endogenous estrogen on ovarian and uterine weight in the immature animals that are used in immature rat uterotrophic assay has not received much attention. In this study, 19-day-old rats were treated with antide, a gonadotropin-releasing hormone antagonist, antide, to block gonadal production of endogenous estrogen. Uterine and ovarian weights of the antide-treated animals were markedly lower than those of control animals. This finding suggests that endogenous gonadal estrogen may already be acting on the uterus and ovaries in immature rats. Blocking endogenous estrogen with a gonadotropin-releasing hormone antagonist may enhance the sensitivity of the immature rat uterotrophic assay; however, the possibility that this protocol may interfere with the ability of the immature rat uterotrophic assay to detect centrally-mediated effects can not be discounted.

Direct Effects of Gonadotropin-Releasing Hormone on the Ovary in Rats and Humans

In order to know whether gonadotropin-releasing hormone (GnRH)-like substances play a role as local regulators in the ovary, localization of the GnRH receptor, and the effects of GnRH agonist (GnRHa) on the cyclic AMP system in the rat ovary was studied. In addition, effects of GnRH antagonist on the rat ovary and effects of GnRHa on steroidogenesis in the human ovary were also examined. In the rat, localization of the GnRH receptor was observed to change with follicular development, and GnRHa decreased follicle-stimulating-hormone-stimulated cAMP production. On the other hand, GnRH antagonist showed the tendency to promote ovarian function. In the human ovary, GnRHa seemed to inhibit steroidogenesis directly, in vivo and in vitro. These data suggested that GnRH/GnRH-like substances play a role as local regulators in the ovary.

Effect of gonadotropin-releasing hormone antagonists on serum follicle-stimulating hormone and luteinizing hormone under conditions of singular follicle-stimulating hormone secretion.

Previous work has indicated that in long-term ovariectomized rats a potent antagonist to gonadotropin-releasing hormone (GnRH) suppressed serum luteinizing hormone (LH) more successfully than follicle-stimulating hormone (FSH). The present studies examined whether the rise in serum FSH which occurs acutely after ovariectomy, or during the proestrous secondary surge, depends on GnRH. In Experiment A, rats were ovariectomized at 0800 h of metestrus and injected with (Ac-dehydro-Pro1, pCl-D-Phe2, D-Trp3,6, NaMeLeu7)-GnRH (Antag-I) at 1200 h of the same day, or 2 or 5 days later. Antag-I blocked the LH response completely, but only partially suppressed serum FSH levels. Experiment B tested a higher dose of a more potent antagonist [( Ac-3-Pro1, pF-D-Phe2, D-Trp3,6]-GnRH; Antag-II) injected at the time of ovariectomy. The analog suppressed serum LH by 79% and FSH by 30%. Experiment C examined the effect of Antag-II on the day of proestrus on the spontaneous secondary surge of FSH, as well as on a secondary FSH surge which can be induced by exogenous LH. Antag-II, given at 1200 h proestrus, blocked ovulation and the LH surge expected at 1830 h, as well as increases in serum FSH which occur at 1830 h and at 0400 h. Exogenous LH triggered a rise in FSH in rats suppressed by Antag-II. In Experiment D proestrous rats were injected with Antag-II at 1200 h and ovariectomized at 1530 h. By 0400 h the antag had suppressed FSH in controls, but in the ovariectomized rats, a vigorous FSH response occurred.(ABSTRACT TRUNCATED AT 250 WORDS)