Delving into the Latest Updates on Gonadotropin releasing hormone(Eunice Kennedy Shriver National Institute Of Child Health And Human Development) with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms-

Target

GnRHR

Mechanism

GnRHR agonists(Gonadotropin-releasing hormone receptor agonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Hypogonadism

Inactive Indication

Kallmann SyndromeProstatic Cancer

Originator Organization

National Institute of Child Health & Human Development

Active Organization

National Institutes of Health

National Institute of Child Health & Human Development

Inactive Organization-

Drug Highest PhaseClinical

First Approval Date-

Regulation-

Luteal phase support (LPS) with progesterone is a generally accepted practice after controlled ovarian stimulation, although the best protocols for LPS have been debated. We aimed to compare the efficacy of vaginal micronised progesterone tablets and 8% vaginal progesterone gel for LPS using real-world data.

METHODS:

This retrospective study included 459 in vitro fertilisation/intracytoplasmic sperm injection cycles performed at a university hospital from 2005 to 2019. All cycles were followed by fresh day 3 embryo transfer (ET). Either progesterone tablets or gel was used for LPS. To control the conditional probability of progesterone tablets or gel use, doubly robust inverse probability weighting composed of inverse-probability-of-treatment weighting (IPTW) and regression adjustment (RA). IPTW was performed based on the covariate balancing propensity score (CBPS).

RESULTS:

Progesterone tablets were administered in 65 cycles, and progesterone gel was administered in 394 cycles. Women who used progesterone tablets were more likely to be older (36 vs. 34 years), have primary infertility (78.5% vs. 61.4%), use gonadotropin-releasing hormone antagonist (60.0% vs. 43.2%), and have fewer retrieved oocytes (seven vs. nine) and transferred embryos (two vs. three) than participants who used progesterone gel. After IPTW-CBPS and RA analysis for the above covariates, the adjusted odds for clinical pregnancy in women who used progesterone tablets were 1.10 times compared with women who used progesterone gel; however, the 95% confidence interval did not reach statistical significance (0.96-1.26).

CONCLUSIONS:

Clinical pregnancy was comparable between vaginal micronised progesterone tablets and vaginal progesterone gel for LPS in fresh day 3 ET cycles.

01 Feb 2025·CELL STRESS & CHAPERONES

Molecular response of canine testis to GnRH agonist: Insights into AR, HIF-1α, and HSPs expression during arrest and recovery of spermatogenesis

Article

Author: Packeiser, Eva-Maria ; Ay, Serhan ; Goericke-Pesch, Sandra ; Findik, Murat ; Speiser-Fontaine, Christelle ; Körber, Hanna ; Selçuk, Murat ; Aslan, Selim ; Vasetska, Anastasiia ; Binli, Firdevs

Slow-release gonadotropin-releasing hormone (GnRH) agonist implants are frequently used for contraception in male dogs. Although the effects are fully reversible, there is still concern about the safety of the implant's mode of action. Addressing this, we investigated cellular stress and androgen receptor (AR) signaling during downregulation and recovery. Testicular tissues were sampled from dogs castrated at different time points after GnRH implant removal and compared with untreated controls. AR, hypoxia-inducible factor 1 (HIF1A), heat shock proteins heat shock protein 72 (HSP72), heat shock protein 73 (heat shock cognate, HSPA8) (HSP73), heat shock protein A2 (HSPA2), heat shock protein 90 alpha (inducible isoform) (HSP90AA1), and heat shock protein 90 beta (constitutive isoform) (HSP90AB1) were investigated by quantitative real-time polymerase chain reaction and AR, HSP72, HSP73, and HSP90 immunohistochemically. While AR, HIF1A, and HSP70 were upregulated at gene expression level, HSPA8, HSPA2, and HSP90AA1 expression were downregulated during spermatogenic arrest; HSP90AB1 expression did not change. Immunohistochemistry verified AR-expression in Sertoli, peritubular, and Leydig cells, occasionally also in spermatogonia. Stress-inducible HSP72 was occasionally detected, while constitutive HSP73 and HSP90 were abundantly expressed by germ cells. Our results were similar to studies on seasonal breeders such as pine voles, geese, fish, and soft-shelled turtles. Accordingly, GnRH implants did not impose additional cellular stress on testicular cells when compared with natural recrudescence. Since comparative data on HIF1α are scarce, we cannot draw conclusions about hypoxic conditions.

01 Feb 2025·Journal of Gynecology Obstetrics and Human Reproduction

Aneuploidy rates and clinical pregnancy outcomes after preimplantation genetic testing for aneuploidy using the progestin-primed ovarian stimulation protocol or the gonadotropin-releasing hormone antagonist protocol

Article

Author: Xu, Aike ; Fang, Lu ; Xu, Wen ; Tong, Xiaomei ; Chen, Bin ; Wang, Xiufen ; Wang, Jieyu

OBJECTIVE:

To investigate the chromosome abnormality rates and clinical pregnancy outcomes after preimplantation genetic testing for aneuploidy (PGT-A) using either the progestin-primed ovarian stimulation (PPOS) protocol or the gonadotropin-releasing hormone (GnRH) antagonist protocol.

METHODS:

The study included 431 PGT-A cycles in which controlled ovarian stimulation was performed using the PPOS protocol (n = 320 cycles) or GnRH antagonist protocol (n = 111 cycles) between January 2018 and December 2021. Frozen embryo transfer was subsequently performed in 307 cycles with transferable blastocysts. The number of retrieved oocytes, embryo development, next-generation sequencing results, and clinical pregnancy outcomes were compared between the two protocols. The primary outcome measure was the aneuploidy rate. Secondary outcome measures were clinical pregnancy per first frozen-thawed embryo transfer cycle and cumulative live birth rates per PGT-A cycle.

RESULTS:

There were no statistically significant between-group differences in the number of retrieved oocytes, available blastocysts, and high-quality blastocyst rate. The aneuploidy rates were similar between the two groups. There was no significant difference in clinical pregnancy outcomes, including the clinical pregnancy, implantation, miscarriage, live birth, or cumulative live birth rates, after frozen-thawed embryo transfer cycles (P>0.05).

CONCLUSIONS:

The study found no significant differences in the aneuploidy rate, clinical pregnancy rate and cumulative live birth rate after PGT-A cycles between those using the PPOS protocol and those using the GnRH antagonist protocol.

1

News (Medical) associated with Gonadotropin releasing hormone(Eunice Kennedy Shriver National Institute Of Child Health And Human Development)

13 Jun 2022

·www.prnewswire.com

Enteris BioPharma Presents Data from Two Clinical Studies Involving Oral Formulations of Leuprolide at ENDO 2022 Annual Conference

Data suggest that oral formulations of leuprolide developed utilizing Enteris' Peptelligence® platform successfully deliver meaningful circulating drug concentrations and achieve hormonal suppressive effects which are comparable to parenteral administration BOONTON, N.J., June 13, 2022 /PRNewswire/ -- Enteris BioPharma, Inc., a biotechnology company developing innovative drug products based on its proprietary delivery technologies, and a wholly-owned subsidiary of SWK Holdings Corporation (Nasdaq: SWKH), announced today that two posters describing clinical studies of oral formulations of leuprolide developed utilizing Enteris' proprietary Peptelligence® platform are being presented at the annual meeting of The Endocrine Society (ENDO 2022) taking place June 11-14, 2022, in Atlanta. Peptelligence is a novel formulation technology designed to enhance the oral delivery and bioavailability of selected drugs by enhancing the permeation of such compounds that are typically injected, including peptides and BCS class III and IV small molecules, and preventing their breakdown in the digestive tract. Leuprolide is a gonadotropin-releasing hormone analogue that is used to treat endometriosis and uterine fibroids in women, prostate cancer in men, and central precocious puberty in boys and girls. The first poster, titled, "Systemic Delivery of Leuprolide via Oral Administration," details the results from a randomized, four-period, four-treatment, crossover pharmacokinetic and food effect study to determine whether Enteris' Peptelligence enteric coating and permeation enhancement is able to deliver therapeutically relevant doses of an oral formulation of leuprolide. The study assessed the PK profiles of 14 healthy female volunteers following single administrations of 1 and 4 mg of leuprolide and compared these profiles to that of a single subcutaneous injection of 1 mg of leuprolide acetate. Data from the study confirmed the successful systemic delivery of leuprolide by the oral route with measures of bioavailability and dose proportionality, as well as revealing an acceptable safety and tolerability profile. The second poster, titled "Effective Suppression of Gonadotropins and Gonadal Steroids Following Oral Administration of Leuprolide," highlights the results from a study testing whether orally delivered low doses of leuprolide could achieve key pharmacodynamic measures, including suppressive effects on luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone. Estradiol suppression is noted as a key indicator for effectiveness in treating hormone-dependent benign gynecologic conditions such as endometriosis. Across all measures, orally administered leuprolide effectively suppressed the gonadal steroids at levels comparable to that of a one-month depot injection of leuprolide (an active comparator in this study), as well as to an approved, marketed dose of a GnRH antagonist. Further, there were no serious or severe adverse events related to the oral formulation of leuprolide. "We are excited to share the results of our studies at ENDO 2022. Both studies have shown positive data on key measures related to the pharmacokinetics and pharmacodynamics of our oral formulation of leuprolide," said Enteris Chief Medical Officer Dr. Gary Shangold. "This is a significant milestone in developing effective oral delivery of leuprolide and there are meaningful applications for underserved patient populations. The depot injection method requires time for its effects to reverse upon discontinuation and may be associated with tolerability issues related to the injection site. Endometriosis can result in multiple painful surgeries, and an orally delivered gonadotropin-releasing hormone (GnRH) agonist could offer significant benefits to patients." In addition to their live presentation at the meeting on Monday June 13th, the full poster presentations will also be available in the virtual format starting on June 11, at 10:00 a.m. ET. Information about ENDO 2022 may be accessed at . About Enteris BioPharma Enteris BioPharma, Inc. is a wholly-owned subsidiary of SWK Holdings Corporation (Nasdaq: SWKH) offering total integrated contract development and manufacturing (CDMO) services including innovative formulation solutions utilizing its proprietary drug delivery technologies, Peptelligence® and ProPerma®. The technologies have been the subject of numerous feasibility studies and active development programs, several of which are in clinical development. Additionally, Enteris BioPharma is advancing an innovative internal product pipeline of drug products that address significant unmet clinical needs for which there is no satisfactory treatment option. For more information on Enteris BioPharma and its proprietary oral drug delivery technologies, please visit . SOURCE Enteris BioPharma, Inc.

Innovative DrugSmall molecular drug

100 Deals associated with Gonadotropin releasing hormone(Eunice Kennedy Shriver National Institute Of Child Health And Human Development)

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2022	Not Applicable	Hormone receptor positive breast cancer	84	gonadotropin-releasing hormone agonists (GnRHa) (OFS plus AI)	zzbcxmevzg(cweksbmqrg) = fmrgwlcnen ojprnlnwfn (zpbhbigrhl )	-	02 Jun 2022
				OFS plus tamoxifen	zzbcxmevzg(cweksbmqrg) = pvbczypoct ojprnlnwfn (zpbhbigrhl )
ESMO2019	Not Applicable	Ovarian Germ Cell Cancer	354	GnRHa group	ybdmdhasac(rzhrfmdhqd) = ltjrayjieq fmecjbbean (qlfciomoeb )	-	29 Sep 2019
				gonadotropin-releasing hormone agonists (non-GnRHa group)	ybdmdhasac(rzhrfmdhqd) = cwzdiusyso fmecjbbean (qlfciomoeb )
ASCO_GU2017	Not Applicable	Prostatic Cancer Neoadjuvant	406	GnRH antagonist + EMP	enpndtutsh(yvftvsymdc) = yrakjdbfau bifgeaabws (iryrqjzebv ) View more	Positive	29 Mar 2017
				LHRH agonist + EMP	enpndtutsh(yvftvsymdc) = xuonilcmjj bifgeaabws (iryrqjzebv ) View more
SABCS2016	Not Applicable	Premenopausal breast cancer Neoadjuvant Ki-67 \| hormone receptor (HR)-positive	332	GnRH agonist + neoadjuvant chemotherapy	jsurowzizy(tuhaegtdzw) = more decreased Ki-67 expression during treatment srrsmbpifs (kdtgctgyiv ) View more	Positive	15 Feb 2016
				Neoadjuvant chemotherapy alone
ASCO_GU2016	Not Applicable	-	3,295	Gonadotropin-releasing hormone agonists (GnRHa)	jcrvyqybpg(zfzyakozfb): HR = 0.8 (95% CI, 0.65 - 0.97) View more	Negative	10 Jan 2016
				gonadotropin-releasing hormone agonists (Bilateral orchiectomy)
ASCO2014	Not Applicable	Premenopausal breast cancer Adjuvant	539	GnRH analogue use shorter than 24 months	ednoijducq(ktolukoxmo) = kqlzfibdrx inwtlqnrun (xlcfkwqwfx )	-	20 May 2014
				GnRH analogue use equal to 24 months	nklagtqmmn(zijshrkmwh) = slagiwarvq mfcnlxpxna (ivwdrgcoig )
NCT01210144 (EXPRESS, CTgov)	Phase 4	Infertility	27	Ovitrelle+Gonal-f (Gonal-f® + Ovitrelle®)	cqrtqdmiuy(jddlkqmwxs) = jqvkgmgvqn zdzmcfoxfs (yqvjrphpjq, klobesvpjt - rvaztttlhx) View more	-	14 Nov 2012
				Ovitrelle+Gonal-f (Gonal-f® + Ovitrelle® (Long Agonist Protocol))	wrufstvebt(pchnvxxelv) = ipoktpqthp vcfueceltu (fbfnilawxa, awxsqlqswz - iyqdfqpzqj) View more
NCT00392756 (Pubmed \| N Engl J Med)	Phase 1	-	624	Low-dose gonadotropin-releasing hormone	rnggihjonx(wpdjoihffj) = All subjects noted breast tenderness gbfcqjhstw (zbdnnwclct ) View more	-	11 Nov 1982