Use Of GnRH Analogues Research Articles

Potency evaluation of different GNRH analogues on ovulation induction and reproductive performance of doe rabbit.

Gonadotropin-releasing hormone (GnRH) -supplemented extenders have emerged as a welfare-orientated method to induce ovulation in the artificial insemination (AI) of rabbits. The main factor that limits the bioavailability of GnRH analogue on intravaginal administration is the proteolytic activity of enzymes present in rabbit seminal plasma. The use of GnRH analogues with higher biological potency would allow us to decrease their concentration in the seminal dose without compromising effectiveness. The current study was designed to assess the efficacy of various GnRH analogues concerning their ability to induce ovulation in rabbit AI. The base solution used for experimental extenders contained an aminopeptidase inhibitor. Four experimental groups were used, females from the Control group were induced to ovulate with an intramuscular administration of 1 μg of buserelin, while in the other three groups females received an intravaginal administration of 3.5 μg of buserelin (BUS), deslorelin (DES) or fertirelin (FER) within the seminal dose. Results showed that the ovulation frequency was similar in all groups studied. A concentration of 3.5 μg of the different GnRH analogues tested in this study showed similar potency in inducing ovulation in non-lactating females, yielding comparable results in terms of pregnancy rate at birth and prolificacy.

Racial Disparities in Medical Management of Uterine Fibroids Prior to Myomectomy or Hysterectomy.

The symptomatic burden of uterine fibroids has been demonstrated to disproportionately affect Black and Hispanic women. The primary aim of this study was to evaluate if racial disparities seen in disease severity in regards to bleeding symptoms and surgical management also applied to presurgical medical management. A retrospective chart review evaluated women aged 18-50 with the diagnosis of fibroids who underwent a myomectomy or hysterectomy between 2012 and 2021. Black and Hispanic women were more likely to have preoperative hemoglobin values under 10mg/dL (p < 0.001) and had higher rates of preoperative blood transfusions than White women (p = 0.001). Black women utilized the highest number of medications before excisional procedures, followed by Hispanic women. Asian women reported the lowest average (p = 0.037). There was no preferential use of GnRH analogues, intrauterine devices, or oral hormonal therapies between races. Minor procedures were infrequently utilized without statistically significant variations among races. This study confirms previous evidence that Black and Hispanic women are more severely affected by uterine fibroids. This severity is mirrored in increased utilization of medications, but patients continue to be under optimized prior to surgery. Further research should identify factors preventing these groups from achieving better symptom control preoperatively.

Assessment of adenohypophysis function and ghrelin level in children with biologically inactive growth hormone syndrome

Background. Mutations in the growth hormone (GH) gene cause various forms of biologically inactive growth hormone (BIGH) syndrome. Ghrelin potentiates the secretion of GH. Ade­nohypophysis hormones take part in human growth mechanisms. Insulin-like growth factor 1 (IGF-1) level is a criterion of GH activity. The purpose of the study was to assess the adenohypo­physis functions and to determine the role of ghrelin in patients with BIGH syndrome to optimize the diagnosis and treatment. Materials and methods. Anthropometric parameters were evalua­ted in 158 children with BIGH syndrome whose average age was 7.83 ± 1.23 years. The function of the adenohypophysis was evalua­ted accor­ding to the levels of somatotropin, thyroid-sti­mulating, adrenocorticotropic, luteinizing, follicle-stimulating hormone and their corresponding peripheral hormones, which were determined by radioimmunological methods and chemiluminescent immunoassay. A statistical analysis of the results was carried out. Results. The release of GH against the background of clonidine and insulin tests in patients with BIGH syndrome was higher than 10 ng/ml, the basal level of IGF-1 was significantly lower than the reference values. After a 4-day test for sensitivity to GH, the level of IGF-1 increased more than 2 times. Against the background of treatment with recombinant GH, serum thyroid-stimulating, adrenocorticotropic hormone, and cortisol indicators changed significantly, but their levels fluctuated within the reference values. Significant changes in ghrelin content were detected 120 minutes after falling asleep. Most children with BIGH syndrome had timely sexual development, precocious puberty was revealed in 19 children, the smallest was the group with delayed puberty (5 children). Gonadotropin-releasing hormone ana­logues were added to the GH treatment in case of unsatisfactory final growth. Conclusions. Normal/high levels of GH and reduced IGF-1 are characteristic of children with BIGH syndrome. In addition, these children have a significant increase in ghrelin in the first hours after falling asleep. The test for sensitivity to GH is a reliable diagnostic method. Thyroid and adrenal disorders were not found in patients with BIGH syndrome. Children with BIGH syndrome have normal sexual development with a tendency to precocious puberty. The simultaneous use of gonadotropin-releasing hormone analogues in combination with GH preparations significantly improves patients’ final growth.

Uterine Leiomyomas and Infertility: A Comparison of National and International Guidelines.

Uterine leiomyomas are the most common benign tumors of the female genital track, causing various symptoms and problems, including a possible impact on fertility.The relationship between fibroids and infertility has long been a debate among gynecologists. Management of fibroids in women with otherwise unexplained infertility worldwide lacks standardized, evidence-based guidelines. Therefore, a review of guidelines from the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the American College of Obstetricians and Gynecologists, the Society of Obstetricians and Gynecologists of Canada, the Collège National des Gynécologues et Obstétriciens Français, and the American Society of Reproductive Medicine was conducted. There is agreement among all guidelines that the effect of fibroids on fertility is related to their position in the uterus and the alteration of the endometrial cavity. However, whether surgical intervention (laparotomy, laparoscopy, or hysteroscopy) is required varies among committees. More specifically, for submucous myomas, all guidelines agree that surgical intervention is needed. On the other hand, regarding intramural myomas, there is no consensus on what the approach may be. Novel treatments such as uterine artery embolization (UAE) and magnetic resonance-guided focused ultrasound surgery (MRgFUS) should only be used in clinical trial settings. Nevertheless, all guidelines agree that medical management of fibroids further delays efforts to conceive and has no role as a stand-alone treatment of fibroids; though, the use of GnRH analogues preoperatively can be useful to improve anemia and/or reduce fibroid volume. There is a need for updated international protocols to be introduced, in order to help clinicians dealing with fibroids and infertility to better suggest the optimal treatment.

Use of GnRH Analog Combined with Parenteral Progesterone Following Intravenous Estrogen Administration in the Treatment of Life-Threatening Dysfunctional Uterine Bleeding: A Case Report

Objective: To report a case of life-threatening anovulatory dysfunctional uterine bleeding (DUB) successfully treated without the use of oral contraceptives

Combined Therapy with Anthracyclines and GnRH Analogues for Breast Cancer: Impact on Ischemic Heart Disease

The combination of classic chemotherapy agents like anthracyclines with novel targeted medications has had a positive impact on women’s survival from breast cancer. GnRH analogues are primarily employed to temporarily suppress ovarian function in premenopausal women with hormone-receptor-positive (HR+) breast cancer. Despite their benefits, the true degree of their collateral effects has been widely understudied, especially when it comes to ischemic heart disease. This review aims at summarizing the current state of the art on this issue, with particular focus on the risk for cardiotoxicity associated with the combined use of GnRH analogues and anthracyclines.

THU194 Growth Pattern And Related Predictors Of Gonadotropin-releasing Hormone Analog Treatment In Girls With Precocious Puberty

Abstract Disclosure: L. Ouyang: None. F. Yang: None. Purpose: The purpose of this study was to analyze the height growth pattern during gonadotropin-releasing hormone analog (GnRHa) treatment in girls with central precocious puberty (CPP) and early and fast puberty (EFP), calculate the incidence of prominent height deceleration and explore the relevant predictors of prominent height deceleration, which may provide useful information for the application of GnRHa as treatement and other adjunctive treatments such as growth hormone (GH). Methods: Ninety-nine girls diagnosed with CPP and 47 girls with EFP were enrolled in this retrospective analysis, they were treated with GnRHa from 6 months to 2 years. Clinical indicators such as hormone levels, bone age (BA), and B-ultrasound indicators were included and shown every 6 months. The growth velocity (GV) of height and the change of height standard deviation score (SDS) were shown every 6 months and once a year. The incidence of height deceleration was calculated in both the first and second years of GnRHa treatment. Multivariate logistic regression analysis was used to explore the predictive indicators of height deceleration. Results: There was a statistically significant difference between girls with CPP and EFP in physical growth indicators, hormone levels, BA, BA advancement, and B-ultrasound indicators at the time of diagnosis (P &amp;lt; 0.05); however, these statistical differences gradually disappeared as treatment progressed. The treatment of GnRHa decreases the GV, BA, and levels of hormones in girls with CPP and EFP. The GV during GnRHa treatment in two groups reached a trough at 18 months, followed by a gradual rebound, but the rebound was significantly greater in CPP than in girls with EFP. The GV of girls with CPP was higher than that of girls with EFP, and the decrease in height-SDS of girls with EFP was more than girls with CPP during the entire of GnRHa treatment. The incidence of growth deceleration in CPP in the first and second year of treatment was 17.35% (17/98) and 42.86% (24/56), and EFP was 25.53% (12/47) and 76.92% (10/13), respectively. No significant indicators predicted the occurrence of growth deceleration (P&amp;lt;0.05). Conclusions: GnRHa is effective in slowing the GV of height, the maturation of BA, and hormone levels in patients with precocious puberty, and the treatment time of 2 years or more can lead to an adult height benefit. The girls with EFP seem to suffer more damage in GV, which might affect AH, so the use of GnRHa in treating EFP should be done with more caution than in CPP. An adequate period of observation in CPP is needed before adjunctive treatments such as GH are used due to the height ascent in the later stage of treatment (18 months to 24 months). None of the factors we studied predicted the incidence of height deceleration during the period of GnRHa treatment. Presentation: Thursday, June 15, 2023

Comparison of the Effects of Dienogest and Leuprolide Acetat on Serum Interferon (IFN-Ɣ) Levels in a Mouse Model of Endometriosis (Mus musculus)

Introduction: Endometriosis is a medical condition in which there is abnormal growth of tissue resembling the endometrium outside the uterus. It can cause symptoms of pain and/or infertility. The current medical therapy focuses on reducing estradiol levels or stimulating progesterone response. One of the most effective options for medical treatment is the use of GnRH analogs. Dienogest have a direct anti-inflammatory effect on endometriotic stromal cells. However, a comparison of the anti-inflammatory effects of these drugs on IFN-Ɣ has not been previously investigated. Therefore, this study aims to compare the effects of reducing IFN-Ɣ by both Dienogest and Leuprolide Acetat in a mouse model. Material and Methods: This study employed a post-test only control group design and involved 4 groups, namely the negative control group, positive control group, and two treatment groups: one group administered Dienogest at a dosage of 0.0052 milligrams per day for 14 days, and the other administered Leuprolide Acetat at a dosage of 0.00975 milligrams once every 5 days for a period of 14 days. Serum IFN-Ɣ levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The data were subsequently analyzed using IBM SPSS 25 with One-Way ANOVA test. Results: This study demonstrated that Leuprolide Acetat significantly decreased serum levels of IFN-Ɣ, whereas Dienogest actually increased the levels . Conclusion: In a mouse model of endometriosis (Mus musculus), Leuprolide Acetat effectively reduced the levels of IFN-Ɣ (pro-inflammatory). Conversely, Dienogest increased the levels of IFN-Ɣ (anti-inflammatory) in the mouse model of endometriosis.

P-680 Oocyte maturation triggering protocols in in vitro fertilisation treatment: a systematic review and network meta-analysis

Abstract Study question What is the relative effectiveness and safety of final oocyte maturation trigger protocols in women undergoing in vitro fertilisation (IVF) treatment? Summary answer OHSS rate was lowest with GnRH agonist trigger and no difference in LBR was observed comparing various trigger protocols in normal, high and poor responders. What is known already Oocyte maturation trigger prior to oocyte retrieval is a crucial component of ovarian stimulation(OS). Pituitary suppression is an important component of OS in IVF, involving the use of GnRH analogues. Currently, the GnRH antagonist regimen is predominantly used given its comparable efficacy and lower risk of OHSS compared with GnRH agonist (GnRHa) regimens. Whilst only hCG trigger can be used with GnRH agonist regimens, GnRH antagonist regimen enables use of hCG trigger, GnRH agonist trigger or combinations of both as dual or double trigger. However, there is no consensus on how these trigger protocols compare in their effectiveness and safety. Study design, size, duration The following databases were searched until August 2022: MEDLINE, EMBASE, CINAHL, CENTRAL and ClinicalTrials.gov. Randomised controlled trials (RCTs) comparing at least two trigger protocols: hCG trigger, GnRH agonist trigger, dual trigger (hCG and GnRH agonist administered at the same time) and double trigger (GnRH agonist followed by hCG after a time interval) with the antagonist regimen were included. Primary outcome was live birth (LBR) per participant. Secondary outcomes included number of oocytes and OHSS rates. Participants/materials, setting, methods Two reviewers independently screened, selected studies and extracted data. Pairwise and network meta-analyses (NMA) were conducted according to ovarian response groups (normal, high and poor response). Effect estimates were presented as weighted means difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) for continuous and dichotomous outcomes respectively. Quality assessment was performed using GRADE Main results and the role of chance Initial searches identified 4225 studies, of which 54 RCTs involving 5838 women met the inclusion criteria to be included in the analysis. In normal responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.11,95%CI:0.83-1.49;3 studies,430 women,I2=33%,low-certainty evidence, direct comparison(DC)),dual trigger vs hCG(RR:1.14,95%CI:0.99-1.31;4 studies,1007 women,I2=33%,low-certainty evidence, DC),double trigger vs hCG(RR:0.53, 95%CI:0.27-1.06;indirect comparison(IC)),dual vs GnRHa (RR:0.97, 95%CI:0.70-1.34, IC),double vs GnRHa (RR:2.07, 95%CI:0.98-4.38, IC),dual vs double (RR:2.14, 95%CI:1.06-4.32;IC). In high responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.04, 95%CI:0.84-1.29; 3 studies,178 women, I2 = 44%, low-certainty evidence, DC, dual trigger vs hCG (RR:1.82, 95%CI:1.25-2.67; 4 studies,117 women, I2 = 37%, low-certainty evidence, DC), double trigger vs hCG (RR:2.10, 95%CI:1.29-3.43, IC), dual vs GnRHa (RR:0.57, 95%CI:0.37-0.88, IC),double vs GnRHa (RR:0.49,95%CI:0.29-0.88, IC),dual vs double (RR:0.87, 95%CI:0.64-1.18; 1 study,57 women, low-certainty evidence,DC). In poor responders, there may be a difference in LBR when comparing dual trigger to hCG (RR:1.12,95%CI:1.12-2.89 1 study,112 women,low-certainty evidence,DC). OHSS rates were lowest with the use of GnRHa in high responders (RR:0.39,95%CI:0.04-3.78;9 studies;960 women;I2 =43%, low-certainty evidence,DC) and normal responders (RR:0.88, 95%CI:0.78 to 0.99;7 studies; 2246 women; I2=0%, low-certainty evidence,DC). There was no significant difference in number of oocytes or miscarriage risks with the use of any triggers. Limitations, reasons for caution Stratifying results by predicted ovarian response resulted in disconnected networks, limiting our ability to perform NMA for certain groups and outcomes. The certainty of the evidence was limited by high risk of bias. Wider implications of the findings Our results suggest that the use of short GnRH agonist trigger results in reduced OHSS rates in women with predicted normal or high ovarian response. There is no difference in LBR and number of oocytes comparing the different trigger protocols in all response groups (normal, high, poor responders) Trial registration number Not applicable

Current treatments for endometriosis in South Korea: an analysis of nationwide data from 2010 to 2019

While a wide range of treatments, including medical therapies and surgery, are used to manage endometriosis, the characteristics and treatment status of patients who received these treatments have not been investigated in Korea. This study analyzed the Korean Health Insurance Review & Assessment Service—National Patient Sample (HIRA-NPS) data from 2010 to 2019 with 7530 patients diagnosed with endometriosis. Annual trends in the types of visit and surgery, medication prescriptions and associated costs were investigated. The analysis showed that surgery slightly decreased among the types of utilized healthcare services (2010: 16.3, 2019: 12.7), dienogest prescription rapidly increased due to national health insurance coverage from 2013 (2013: 12.1, 2019: 36.0), and the use of gonadotrophin-releasing hormone analogues decreased (2010: 33.6, 2019: 16.4). There was no significant change in total and outpatient costs per person over time. Regarding endometriosis treatment, conservative treatment mainly based on prescribed medications has been gradually replacing surgery. Particularly, the listing of dienogest for national health insurance coverage might have affected the trend. However, there were no significant changes in terms of total and medication costs per person.

A Case Report of Laparotomic Myomectomy After The Use of Gnrh Analogue in A Brazilian Woman

Uterine leiomyoma is the most common genital benign tumor in the female population. It is estimated that about 20 to 40% of women will have leiomyoma during their reproductive stage. IBGE (Brazilian Institute of Geography and Statistics) estimated the Brazilian population to be over 200 million Brazilians, of which half are women and approximately 50% are of reproductive age; hence, by calculating the prevalence of leiomyomatosis, there would be just over 6 million women with symptomatic fibroids in Brazil that require clinical or surgical treatment.[1-3-4] Due to its presence during the reproductive period, it can be caused by infertility or recurrent spontaneous pregnancy loss. Hence, myomectomy can be necessary when the fibroid itself causes distortion of the endometrial cavity, or competes with the embryo for the same place, or when conservative treatment was ineffective. This report describes a case of myomectomy which was performed after treatment with goserelin acetate with considerable reduction of fibroids volume, probably facilitating surgical approach, decreasing the blood loss and the risk of hysterectomy conversion. In addition, other GnRH analogue benefits before surgery such as doctor’s impression of decrease in size and better mobility of the tumor and patients feeling of decrease of the abdominal volume and the bleeding. This subjective approach can optimize the timing of surgery and establish the number of injections.

Gonadotropin-Releasing Hormone (GnRH)/GnRH Receptors and Their Role in the Treatment of Endometriosis.

Endometriosis, defined as the development of endometrial tissue outside of the uterine cavity, is a common gynecological disorder. The prevalence of pelvic endometriosis approaches 6%-10% in the general female population, and in women with pain, infertility, or both, the frequency is 35%-50%. The gold standard recommended process for diagnosing endometriosis is laparoscopy, an invasive surgical procedure, with or without histologic verification. The currently available nonsurgical treatments include oral contraceptives (estrogen-progestogen preparations), progestogen preparations (containing progesterone derivatives), androgenic hormones (danazol), and gonadotropin-releasing hormone (GnRH) agonists and antagonists. Two GnRH types have been discovered in mammals, GnRH I and GnRH II. In particular, GnRH I is released by the hypothalamus; however, it can be present in various tissues and organs of the body, including neural tissue, where it exerts neuroendocrine, autocrine, and paracrine actions in the peripheral and central nervous system (CNS). Interestingly, another GnRH isoform, GnRH III, has been identified, which has 60% similarity with GnRH I from which it varies by four amino acids. This peptide has been shown to have a significant role in reproduction, specifically in gametogenesis and steroidogenesis. Further research is needed to identify innovative treatment options for endometriosis, such as the therapeutic exogenous administration of GnRH II or antagonists of the GnRH I receptor. In this review, we examined the role of GnRH in endometriosis, outlining the specific actions of GnRH and GnRH receptors (GnRHRs). The innovative use of GnRH analogs and antagonists in the treatment of endometriosis is also discussed.

A Retrospective Study of the Use of Gonadotropin-Releasing Hormone Analogs and Testosterone in Transgender Boys: Who, What, When, and for How Long?

A retrospective review of gender-affirming hormone therapy was conducted in 101 transgender boys followed in the pediatric endocrine clinic. Eighty-seven percent were postmenarchal at the initial visit. Of the 44% prescribed gonadotropin-releasing hormone analogs (GnRHas), insurance coverage was denied in 34% and an average of 4.5 months elapsed before treatment could be started in the remainder. Patients prescribed GnRHas were younger than those who were not, 13.7±2.1 versus 15.5±2.0 years, p<0.001. Continued menstrual bleeding was reported by patients receiving testosterone alone at doses ranging from 50 to 200 mg every 2 weeks.

Mitigating the economic burden of GnRH agonist therapy for progestogen-resistant endometriosis: why not?

Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens? An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief. Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted. A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected. Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded. Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or 'draw-back' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%). The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed. Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access. This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. N/A.

GnRH analogs for the treatment of heavy menstrual bleeding associated with uterine fibroids

Treatment of heavy menstrual bleeding associated with uterine fibroids (UF) is evolving. Historically, treatment options were limited to predominantly invasive surgery; today, conservative and novel oral medical treatments are widely available for use with significant efficacy. This evolution was directly driven by our improved understanding of UF pathophysiology. Specifically, our recognition of the hormone-mediated pathway in UF development and growth laid the framework for using GnRH agonist analogs in treating UF. In this report, we explore the use of GnRH analogs in the treatment of heavy menstrual bleeding associated with UF in phases. We review historical perspectives, discuss the development and use of aternatives to GnRH analogs, a period we refer to as the "Dark Ages" of GnRH analogs, we then provide an overview of the later years and present-day use of GnRH analogs and discuss opportunities for future directions.

Effect of the Use of GnRH Analogs in Low-Grade Cerebral Glioma

Low-grade gliomas are children’s most common brain tumors, presenting a wide range of clinical, histological, and biological behavior. Estrogens and progesterone are steroid hormones. In recent years, there has been speculation about its relationship with its role in the development of tumors. We describe the case of a 2-year-old girl with a low-grade brain tumor treated with chemotherapy without changes in its measurements. Initiated treatment with Decapeptyl® due to precocious puberty presents a decrease in its solid component, more than 50% of the initial size three years after starting treatment. Various studies have described the influence of estrogen and progesterone on the development of gliomas, decreasing or increasing their expression in those tumors of greater aggressiveness, respectively. Despite the study of the tumor-hormonal expression relationship in other types of tumors, in brain tumors, its role in their treatment remains to be known.

RF33 | PSAT68 Gonadotropin-Releasing Hormone Agonist Therapy Does Not Affect Bone Mineral Density in Congenital Adrenal Hyperplasia: a Clinical Study

Abstract Background Children with congenital adrenal hyperplasia (CAH) are at risk for early central puberty, and gonadotropin-releasing hormone analogs (GnRHa) are frequently used aiming to improve adult height. However, their effect on bone health among the CAH population has not been previously studied. GnRHa reduce sex steroid levels and delay central puberty, which may negatively affect the achievement of peak bone mass. In healthy children, bone mass increases with time, reaching its peak between the second and third decades of life. The purpose of this study was to investigate the short-term and long-term effect of GnRHa therapy on the bone mineral density (BMD) of patients with classic CAH. Methods Sixty patients with classic CAH due to 21OH deficiency were followed longitudinally at our institution with DXA scans at the time they achieved adult height. Adult height was considered attained when bone age exceeded 15 years in girls and 17 years in boys. Twenty-one patients treated with GnRHa (81% male, 57% salt wasting, treated for mean ± SD: 4.3 ±2 years) were compared to 39 patients not treated with GnRHa (49% male, 79.5% salt wasting). BMD z scores, adjusted for height and age, were evaluated at the time they reached adult height and on average 8.3 years later. Results There was no difference between GnRHa groups in total body (p=0.96), femoral neck (p=0.24), lumbar spine (p=0.59), forearm (p=0.38), and total hip (p= 0.31) z scores at adult height attainment. In multivariable analyses, there was no effect of GnRHa on BMD z scores at any site. In reduced models, increased 17-hydroxyprogesterone (17-OHP) levels correlated with higher BMD z scores for total body (p=0.003), lumbar spine (p&amp;lt;0.001), and forearm (p&amp;lt;0.001). Higher BMI (p=0.014) and no treatment with dexamethasone (p=0.022) were also associated with higher femoral BMD z score. Overall, the follow up DXA during young adulthood (n=28) showed significant decreases in z scores at total body (p=0.019), femoral neck (p=0.036), lumbar spine (p&amp;lt;0.001), forearm (p&amp;lt;0.001), and total hip (p=0.024), and use of GnRHa did not contribute. Interestingly, when adjusting for midparental height, those treated with GnRHa had lower adult height z scores than those without GnRHa (p=0.037). Conclusion Treatment with GnRHa for approximately 4 years does not impact BMD in adolescents and young adults with CAH, and exposure to adrenal androgens may play a protective role. In patients with CAH, BMD decreases with time and during the second and third decades of life, which may reflect the effect of long-term supraphysiologic glucocorticoid therapy. Although intended to preserve height, children with CAH who experience early puberty have loss of adult height, despite treatment with GnRHa. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:54 p.m. - 12:59 p.m.

Analysis of the effectiveness of the GnRH analogue use in the protocol of superovulation of donor cows

The aim of the study was to estimate the effectiveness of the drugs containing a synthetic analogue of gonadotropin-releasing hormone (hereinafter referred to as GnRH) and to determine the best drug that stimulates the follicle ovulation in the ovaries of donor cows for obtaining the maximum number of high-quality embryos. The hormone stimulation of donor cows was carried out in Centre for Reproductive Technologies, LLC (Syreyka, Kinel district, Samara region) in the period from 2018 to 2022. The cows that were treated beforehand with follicle-stimulating hormone and having three or more dominant follicles were selected for the experiment (n=264). Three groups were formed depending on the GnRH product. In group I (n=31), we administrated "Fertagil" intramuscularly at a dose of 2.5 ml per animal. In group II (n=132), the drug "Veterlin" was applied and also at a dose of 2.5 ml per animal. In group III (n=101), the drug "Surfagon" was used at a concentration of 10 micrograms and at a dose of 5 ml per animal. 12 and 24 hours after administration of the drug, artificial insemination of donor cows was performed by the rectocervical method. Embryos were flushed on the 7th day of the induced estrus cycle. During the morphological evaluation of the obtained embryos, it was found that the largest number of high-quality embryos was detected in group II, where we used "Veterelin". When recalculating the total number of high-quality embryos on average per donor, this indicator was 8.7 embryos, which significantly exceeded the results obtained in group I by 1.2 pcs. (PЈ0.05) and in group III - by 1.4 pcs. (PЈ0.01).

Type of endocrine therapy and DFS in patients with early HER2+/HR+ BC: Analysis from the phase III randomized ShortHER trial.

547 Background: Optimal adjuvant endocrine therapy for HER2+/HR+ patients treated with chemotherapy and trastuzumab is still unclear. We evaluated the impact of the type of endocrine therapy on DFS in patients with HER2+/HR+ breast cancer enrolled in the phase III ShortHER trial. Methods: The Short-HER study randomized 1254 patients with HER2+ early breast cancer to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with anthracycline-taxane chemotherapy. The type of adjuvant endocrine was collected every 6 months during the first 5 years of follow-up and was classified as: aromatase inhibitor (AI), tamoxifen and aromatase inhibitor (TAM-AI, in case of both drugs were administered for at least 1 year each), or tamoxifen (TAM). For premenopausal patients, the use of GnRH analogue was also collected. DFS was calculated from randomization to disease recurrence (locoregional or metastatic), second primary invasive cancer, or death. Results: 853 patients with HR+ BC (ER and/or PgR &gt;10%) were included: 60% postmenopausal, 40% premenopausal. The pattern of endocrine therapy was: 55% AI, 22% TAM, 15% TAM-AI (8% missing data). Among premenopausal patients, 51% received GnRH. At a median follow up of 8.7 years (IQR 7.6-9.0), patients who received AI had a significantly better DFS as compared to patients who received TAM or TAM-AI: 7-yr DFS 87.3% vs 81.7%, log-rank P=0.017 (HR 1.46, 95%CI 1.05-2.03). In multivariate analysis including menopausal status, stage, and treatment arm, the type of endocrine therapy maintained a significant association with DFS (Table). In the subgroup of premenopausal patients, the use of GnRH was associated with numerically improved DFS: 86.6% vs 81.6%, log-rank P=0.168 (HR=0.70, 95%CI 0.43-1.16). Conclusions: In this post-hoc analysis of the ShortHER trial, adjuvant treatment with aromatase inhibitor was independently associated with improved DFS. Subgroup analysis in premenopausal patients suggests potential benefit with ovarian suppression. Clinical trial information: NCT00629278. [Table: see text]

Efficiency of using bioregulators depending on the system and method of keeping of cows

Relevance. For the reproduction of the breeding stock of cattle, the conditions of detention should maximally meet the optimal conditions for the life of animals. In this regard, the study of the characteristics of physiological changes after injections of bioregulators to induce estrus in cows under various systems and methods of keeping is of great importance and is an important area of research. The purpose of the work is to study the reproductive function of cows depending on age and various conditions of keeping.Methods. The results of the work are based on analytical, biometric, statistical methods and the authors’ own research.Results. In studies was found that a general decrease in the effectiveness of the use of GnRH analogs and hCG to increase fertility can occur due to treatments carried out in the summer months. The greatest effect of the use of GnRH and hCG preparations should be expected when they are introduced in parallel with insemination in induced estrus in the winter-spring and autumn-winter months. At the same time, the fertility rates in cows tethered were slightly higher in the stall-pasture system of keeping, and slightly lower in the camp-pasture system than in loose ones. When studying the reproductive function, depending on the number of lactations, as a result of the use of a complex of bioregulators, high indicators of cows that came into the hunt were obtained, from 74 to 91% of the total number of animals showed signs of estrus according to the different number of lactations. Cows with 1st and 2nd lactation have the highest rate for those who came into heat (91% and 87%) with the lowest insemination efficiency (47% and 49%, respectively). In cows of the 3rd and 4th lactations, the highest adjustment to the restoration of the ovarian cycle is observed, with the average indicators of those who came to the hunt, the highest insemination efficiency was subsequently obtained (70 and 75%, respectively). For three or more months after calving, more than half of the herd of calving cows (71.6%) were fruitfully inseminated.