Cetrorelix 3mg powder and solvent for solution for injection vials

Background Aberrant vascular endothelial growth factor (VEGF)–driven angiogenesis is central to the establishment and persistence of endometriosis. Although numerous anti-angiogenic compounds have been tested, evidence remains fragmented, and no comparative framework guides the selection of agents compatible with fertility preservation. Objective To identify and rank vascular-targeted pharmacotherapies that most effectively regress endometriotic lesions and could be prioritised for fertility-sparing clinical translation. Methods We conducted a systematic review and frequentist network meta-analysis (PROSPERO CRD420251082905) of controlled studies evaluating VEGF-directed agents in endometriosis. Six databases and two trial registries were searched from inception to 28 July 2025. Thirty-one studies met inclusion criteria (five early-phase human trials, six patient-derived cell models, two baboon experiments, and 18 rodent experiments) investigating 23 pharmacological agents. Primary outcomes were lesion area, lesion number, and VEGF expression; secondary outcomes included microvascular density, endometrial cell proliferation, and apoptosis. Random-effects pairwise and network models (R 4.3 “netmeta”) generated standardised mean differences (SMDs) with 95% CIs and SUCRA rankings. Transitivity, heterogeneity ( τ 2 , I 2 ), and inconsistency were formally assessed. Drug–gene target intersections across six cheminformatic databases mapped mechanistic convergence. Results Curcumin achieved the greatest lesion-size reduction (SMD = −1.08, 95% CI = −1.38 to −0.79) and the steepest fall in microvascular density (−16%), while cetrorelix most effectively reduced lesion number (SMD = −0.78, 95% CI = −1.36 to −0.20). Retinoic acid and bevacizumab halved VEGF expression. Global inconsistency was non-significant ( P > 0.18) and heterogeneity moderate ( I 2 ≤ 65%). A network analysis identified a 16-gene hub ( CASP3 , MAPK1/3 , AKT1 , STAT3 , etc.) underpinning effective drugs; curcumin targeted 14 of these nodes. Limitations Fifty-eight per cent of the data derived from rodent models revealed that these models do not menstruate and incompletely recapitulate human endometriosis. Most experiments reported short-term surrogate outcomes and rarely measured pain, fertility, or quality of life. Risk of bias was frequently moderate to high, and therefore, small-study or publication bias cannot be excluded. Conclusion This study provides the first, exploratory comparative synthesis of VEGF-directed pharmacotherapies for endometriosis across pre-clinical and early-phase human models. Apparent efficacy rankings, including the high placement of curcumin, should be interpreted as relative signals within a limited and biased dataset rather than as evidence of inherent biological superiority or clinical readiness. These findings are best viewed as hypothesis-generating and may assist in prioritising agents for more rigorous translational and clinical research, rather than supporting specific treatment recommendations. Systematic Review Registration PROSPERO CRD420251082905.

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OBJECTIVE: This study is aimed to determine the efficacy of a cocktail style treatment by combining GnRH-antagonist, letrozole, and mifepristone on the prevention of ovarian hyperstimulation syndrome (OHSS) in high-risk women. METHODS: This prospective, randomized controlled clinical trial was performed between January 2018 and December 2018. A total of 170 women who identified as high risk of OHSS during the ovarian hyperstimulation and underwent cryopreservation of whole embryos. On the day of oocyte retrieval, the combination group received 0.25 mg Cetrorelix for 3 d, 5 mg letrozole for 5 d, and 50 mg mifepristone for 3 d, the mifepristone group received 50 mg mifepristone for 3 d. A total of 156 cases were included in final analysis. All the frozen embryo transfer (FET) cycles were followed up until December 2021. RESULTS: . 76.9%). CONCLUSIONS: The combination treatment effectively reduces the incidence of moderate/severe OHSS in high-risk women.

Abstract licence: CC BY-NC

Background: Assisted reproductive technology (ART) protocols can lead to a serious and potentially life-threatening complication known as ovarian hyperstimulation syndrome (OHSS). The present study investigated and compared the effects of gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) administration over 3-day and 7-day periods in women at high risk for OHSS. Methods: In this prospective randomized controlled pilot trial, an antagonist protocol was employed as part of ART in 41 patients aged 18 to 40 who were referred to the Infertility Center. After egg retrieval, subjects in group 1 received cabergoline in combination with 7 days of cetrorelix (one subcutaneous ampoule of cetrorelix once daily), while participants in group 2 received cabergoline along with 3 days of cetrorelix (one subcutaneous ampoule daily). Upon enrollment, participants were administered cabergoline tablets (Cabergolex 0.5 mg) at a dose of 0.5 mg orally at bedtime for 8 consecutive days. Ultrasound and clinical examinations were performed on the day of oocyte retrieval and on days 4, 8, and 14 thereafter to detect the occurrence of OHSS. Data were analyzed using SPSS version 22, with independent samples t-test and Chi-square test conducted at a significance level of <0.05. Results: The patients in the 3-day treatment group were aged between 30.30 ± 6.46 years, while those in the 7-day treatment group were between 29.09 ± 5.59 years, with no statistically significant difference between themean groups (p = 0.528). No hospitalizations were necessary in either the 3-day and 7-day treatment groups, and no cases of severe OHSS were observed. Moderate OHSS occurred in 6 patients (20%) in the 3-day treatment group and 5 patients (23.8%) in the 7-day treatment group, with no statistically significant difference between the groups (p = 0.768). Conclusions: A 3-day treatment appears to be as effective as a 7-day treatment in preventing OHSS. Clinical Trial Registration: This study is registered on the Iranian Registry of Clinical Trials (IRCT) at https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20201126049497N1 (registration number: IRCT20201126049497N1).

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Background: The symptoms of ovarian hyperstimulation syndrome (OHSS), an unintentional and possibly lethal side effect of ovarian stimulation in assisted reproductive technology (ART), include rapid movement of fluid from the blood vessels to the space outside the blood vessels and tissue spaces, such as the abdominal cavity and cystic enlargement of the ovaries. Aim: Evaluating the efficacy of the GnRH antagonist (GnRHant) cetrorelix in the treatment of early-onset severe OHSS after controlled ovarian hyperstimulation (COH) versus standard management of OHSS. Patients and Methods: This randomized controlled clinical trial included 60 women who developed early-onset severe OHSS after COH presenting to the casualty/outpatient clinic at Alazhar University. They were split up into two groups at random. Group A received standard management of severe/critical OHSS, and Group B received standard management plus cetrorelix. Results: Although the proportions of women requiring initial paracentesis, elevated serum creatinine, or experiencing oliguria were alike between the two groups, women in Group II (cetrorelix group) demonstrated significantly better outcomes. Specifically, the need for repeat paracentesis, mean serum creatinine levels at 48 hours, and the incidence of persistent oliguria after 48 hours were notably lower in Group II compared to Group I (control group). Moreover, both the average length of hospital stay and the mean time to recovery were significantly shorter among women in the cetrorelix group. Conclusion: Using GnRH antagonist as cetrorelix acetate 0.25 mg SC injection once per day in addition to standard management was an effective therapy in women with early OHSS after controlled ovarian hyperstimulation.

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Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists' clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases.

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Abstract Nasal sprays are extensively researched due to their rapid absorption, high bioavailability, and low side effects. Lipid liquid crystal nanoparticles (LLCNs) are being considered as potential carriers for intranasal delivery. LLCs loaded with cetrorelix (GnRH antagonist) were utilized for intranasal drug delivery to enhance brain targeting while minimizing systemic exposure. A single-phase formulation incorporating HPMC as a mucoadhesive was developed to extend nasal residence time. Following intranasal administration of cetrorelix in rats, its distribution in various brain regions and serum was assessed using LC–MS-MS. In the LLC formulation, the particle diameter, PDI, and Zeta potential were measured as 204.92 ± 0.89 nm, 0.188 ± 0.019, and -21.63 ± 1.72 mV, respectively. A monomodal distribution and low polydispersity index were observed, along with a negative zeta potential. Cetrorelix was released from the LLC in a biphasic profile, with an initial burst release of 30%, followed by a gradual and sustained release phase. The LLCs containing cetrorelix exhibited lower cytotoxicity compared to the LLC base. The nasal administration of cetrorelix via LLCs presents a promising advancement for nose-to-brain drug transport. The pharmacokinetic data demonstrated that the AUC 0-360min for brain tissue analysis, following nasal administration of the single-phase formulation, was 3.104 ng/ml.min. The value was 7.104 ng/ml.min for LLC nasal administration and 6.104 ng/ml.min for subcutaneous injection. The maximum concentration (C max ) values for brain tissue analysis indicated a significant increase with LLC nasal administration (238 ± 6. 2 ng/ml) in comparison to the single-phase formulation (202.5 ± 6.3 ng/ml) and subcutaneous injection (218.2 ± 3. 1 ng/ml). In serum analysis, the C max values were significantly elevated, with subcutaneous injection achieving (4983.3 ± 2.5 ng/ml), followed by LLC nasal administration at (93.1 ± 6.2 ng/ml), and the single-phase formulation at (43.7 ± 2.2 ng/ml). This innovative method aims to target the brain directly, eliminating the need for needles, and reducing adverse effects, hence offering new hope for brain-targeted drug delivery. This study introduces, for the first time, a cetrorelix-loaded lipid liquid crystal (LLC) nanoparticle formulation for intranasal nose-to-brain delivery. The LLC system achieved enhanced brain targeting efficiency while reducing systemic exposure compared to conventional subcutaneous injections and simple nasal formulations, representing a promising advancement in GnRH drug delivery strategies. Graphical Abstract

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