{"paper_id":"15030168-0f7b-4f06-9ada-3a2795fe0b8c","body_text":"J Clin Anesthes Res\nVolume 2 • Issue 1 • 7\nJournal of \nClinical Anesthesiology Research \nPaul J, et al., J Clin Anesthes Res 2021, 2:1\nElagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis\nJoyson Paul, Rohit Bhatia*\nDepartment of Pharmaceutical Analysis, ISF College of Pharmacy Moga, Punjab, India-142001\n       ABSTRACT\n Endometriosis is a category of lesions and fibroids which occur in the innermost lining of the uterus that is the \nendometrial layer and spreads to the other parts of the neighboring tissues. It is characterized by inflammation, \npelvic pain, menstrual bleeding, and Dysmenorrhea. Endometriosis exists in 3 forms based on its spreadability. i.) \nsuperficial peritoneal lesions ii.) deep infiltrating lesion and iii.) cyst. Traditional treatments involve are NSAIDS, \nOral contraceptives, Aromatase inhibitors, and GnRH agonists. Elagolix emerges out to be the latest potent drug \nthat acts by inhibiting the GnRH receptor. Unlike other allopathy medicine, it is not an asymptomatic pain reliever \nbut acts on the root cause of the disease. FDA has approved it for specific treatment of endometriosis in July \n2018. It is believed that endometriosis occurs by an increase in the production of estrogen. Elagolix competitively \nbinds to the GnRH receptors and prevents the binding of the Gonadotropin hormone flowing through blood \ncapillaries from the Hypothalamus to the pituitary gland and thereby stops the formation of Oestrogen in the \nreproductive system which ultimately ceases in the proliferation of endometrial layers and tissue spread. In \nestrogen biosynthesis, the aromatase P450 enzyme plays a vital role. Elagolix belongs to BCS class III and available \nin the oral dosage form of 150, 200mg. It is rapidly absorbed and Cmax reaches within 1hour. The plasma protein \nbinding is 80%. In this review, various aspects related to Elagolix sodium have been summarised, which include \npathophysiology, Mode of Action, Structure-activity relationship, Pharmacokinetics, pharmacodynamics, and \nclinical studies with minimal side effects. \nKeywords: \n  Endometriosis, GnRH antagonist, Elagolix sodium, Aromatase \nP450, Estrogen, Fibroids.\nIntroduction\n  Endometriosis is a disease that occurs in the innermost \nlining of the Uterus, where the proliferation of cells leads to \nthe formation of fibroids. Endometriosis is a non-cancerous \nuterine Leiomyoma which is the outgrown tissues in the \nendometrium layer [1].It is defined by a benign inflammatory \ndisease characterized by ectopic endometrial glands and \nstroma [2]. Endometriosis occurs with no specific symptoms \nand affects around 5-10% of women in their active menstrual \ncycle [3,4]. Approximately 175 million females worldwide are \nsuffering from this deadly disease which is estimated to be 1 \nin 10 women is affected by endometriosis between the age \nof 15 to 49 [5]. Brown et al. says that more than 1.8 billion \nwomen receive the diagnosis of endometriosis. Endometriosis \nspread from superficial peritoneal lesion to cysts in the ovaries, \nmyometrium and even it spreads to the rectum. Based on its \nseverity of spreading the disease endometriosis is classified into \n3 subtypes: (i)superficial peritoneal lesions, (ii)deep infiltrating \nlesions, and (iii)cysts. The superficial peritoneal lesions are thin \nfilm that coats the inner surface of the pelvic cavity [6]. \n The 90% chances are during menstruation the pieces of \nendometrium reflux in the abdominal cavity through fallopian \ntubes adhere to the peritoneal lining and develop into lesions \n[7]. In rare cases the superficial peritoneal transformation may \nturn into malignancy [8]. Deep infiltrating lesions are the second \nform of endometriosis where small fibroids of 5mm size were \nfound penetrating the peritoneal surface it is characterized by \nstroma and ectopic endometrial glands and the disease known as \nAdenomyosis. It spreads to the posterior area, the cervical part \nto the posterior wall of the vagina, and the wall of the rectum \n[6]. Cyst is a third form of endometriosis because it originates \nfrom the inner lining of the uterus and spreads to the ceiling of \nthe ovarian fossa therefore is called an ovarian endometrioma. \nThe chances of spreading in ovaries are 17-44%. It is often \nassociated with pelvic pain and heavy bleeding. The heavy \nbleeding and severe pelvic pain are due to GnRH, inflammation, \nand dyspareunia. The susceptibility of endometriosis is 5 times \nmore in those women having dyspareunia.\n Also, Women diagnosed with endometriosis has 80% chances \nof dysmenorrhea and 40% chances of infertility [9]. The possible \ncause of endometriosis is the overexpression of the enzyme \naromatase cytochrome P450 which is responsible for the growth \nof estrogen and converts androgens into estrogen which plays a \nvital role in the formation of the endometrium layer. Aromatase \nReview Article\nCorrespondence to: Rohit Bhatia, Department of Pharmaceutical Analysis, ISF College of Pharmacy Moga, Punjab, India-142001; Email: Bhatiarohit5678@gmail.com\nReceived date: May 2, 2021; Accepted date: May 15, 2021; Published date: May 22, 2021\nCitation: Paul J, Bhatia R (2021) Elagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis. J Clin Anesthes Res 2(1): pp. 1-6. doi:10.52916/jcar214007\nCopyright: ©2021 Paul J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted \nuse, distribution and reproduction in any medium, provided the original author and source are credited.\nPage 1 of 6\n\nJ Clin Anesthes Res\nVolume 2 • Issue 1 • 7\nCitation: Paul J, Bhatia R (2021) Elagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis. J Clin Anesthes Res 2(1): pp. 1-6. doi:10.52916/jcar214007\nPage 2 of 6\nP450 is regulated by the tissue-specific promoters present in the \nplacenta (promoter I.1), adipose tissue (promoters I.4, I.3), and \ngonads (promoter II). The population of the Aromatase arises in \nthe use of each promoter [10]. Through mRNA transcription the \nmajority of P450arom are transcripts into the cells contained \ngonadal type promoter II and very few in other cells. Because \nof the inflammatory nature of endometriosis [11], it was \nfound that Prostaglandin receptors stimulate the P450arom to \npromote estrogen production [12]. PGE2 is responsible for the \nincrement in endometrium stromal cells by 19 to 44 times in \nthe production of P450arom. Therefore, PGE2 is potentially the \nprimary stimulator of P450arom. As PGE2 stimulates the stromal \ncells of endometriosis, the promoter II of gonads over-regulates \nthe cAMP pathway and increases the intracellular concentration \nlevel which leads to the production of estrogen and ultimately \nleads to inflammation, lesion and fibroids in the later stage.\nPathogenesis\n The exact pathogenesis of endometriosis is still unclear and \nmany researchers gave their theories but out of them only four \ntheories are popular and explain the pathogenesis to some \nextent [13].\n 4 popular theories believe to explain the pathogenesis of \nendometriosis:\n• Retrograde menstruation\n• Vascular and lymphatic dissemination \n• Impaired immunity\n• Hereditary and stem cells\nRetrograde menstruation \n  Retrograde menstruation is also called Sampson’s theory which \nstates that during menstruation the remains of endometrial \ntissue back trap into the fallopian tube and reach to the ovaries \nwhich causes inflammation and outgrown tissues. The tissue \nback trap is called the retrograde flow. And therefore, repeated \nretrograde flow led to the formation of the fibroids. Sampson’s \ntheory failed to explain that why endometriosis occurs in only \n10% of women when retrograde menstruation is found in 80% \nof women. \nVascular and lymphatic dissemination\n This theory says many lymphatic blood vessels provide blood \nsupply into the uterine endometrial layer and other parts of the \nreproductive system. It is believed that some of the tissues of \nthe endometrial layer go into the blood vessels and travels to \nthe fallopian tube, ovaries, and pelvic region and this repeated \nprocess promote the formation of endometriosis. \nImpaired immunity\n Endometrial tissue starts to pour out of the uterine tube into \nthe pelvic region as it deposits the endometrial tissue. The \nwhite blood cells reach the pelvic region. They bind with the \nhaptoglobin proteins found in the patients of endometriosis \nand increase the Interleukin production. Other cytokines that \nmigrate to the peritoneal fluid include macrophage migration \ninhibitory factor, TNF-alpha, IL-1beta, IL-6, IL-8. The growth \nfactors of PGE2 cause adhesion, proliferation, and inflammation. \nThe white blood cells destroy the endometrial layer instead of \noutgrown endometrial tissues present in the peritoneal layer, \nfallopian tube, and ovaries. Because WBCs are unable to detect \nHereditary \n A theory says if a mother had endometriosis it is likely to have \nthe same disease in her daughter as well. But the problem with \nthat is there is plenty of cases that prove this theory 100% \ncorrect.\nStem cells \n Inside of endometrium, there are a bunch of stem cells that \nare undifferentiated and can regrow after a while. They renew \nto form the endometrium layer. These stem cells reach the \nfallopian by retrograde menstruation and due to the ability \nto renew they grow and form fibroids and ultimately cause \nendometrioses. \nPathophysiology\n Due to inflammation in the neighbouring tissues by various \npathogenesis theories, the excess production of Prostaglandin \ntriggers the Aromatase enzyme P450 to increase the reaction \nrate and formation of estrone from androstenedione which is a \nfirst estrogen. The pathophysiology of endometriosis has been \noutlined in figure 1.\nTreatment\n The first-line treatment of endometriosis is some drugs that work \non the symptoms of endometriosis. For the first-line treatment, \nwe use NSAIDS for pelvic pain relief and dysmenorrhoea. Most \ncommonly used among NSAIDs are ibuprofen, aspirin, and \nnaproxen [15]. However one study revealed a low positive effect \nof NSAIDs on pain relief in women suffering from endometriosis \n[5]. The other first-line drugs are combined oral contraceptives. \nSecond- and third-line drugs for treatment are progestins, an \naromatase inhibitor, and a GnRH agonist. GnRH agonists are \nnot recommended to adolescents because of their effect on \nbone. Aromatase inhibitor shows good results by decreasing \nthe production of estrogen and cessation of the menstrual \ncycle during endometriosis in women [16]. Studies showed that \nprolong use of aromatase inhibitors cause decrease in bone \nmineral density. \nGnRH antagonist \n Elagol ix is a GnRH antagonist and works opposite to GnRH \nagonist in which downregulation leads to desensitization of the \nreceptor and the therefore the release of estrogen decreases \nand ceases in the formation of the endometrium layer. Elagolix \nbelongs to a class of fluorinated carbons [17]. Elagolix is in the \nearly stages of treating heavy menstrual bleeding and uterine \nleiomyoma. The drug is known by its brand name ORILISSA and \nis manufactured by the neucrine and Abbvie Inc. \nPregnenolone O2, NADPH 17alpha Hydroxy Pregnenolone Oxidation Dehydrepindrosterone\nTautamersim Oxidation\nAndorstenedione\nEstrone\nAromatase P450 Oxidation\nEstradiol\nInflamation\nPGE2\nExcess Production\nFigure 1: Pathophysiology of Endometriosis.\n\nJ Clin Anesthes Res\nVolume 2 • Issue 1 • 7\n Page 3 of 6\nChemistry\n The structure and synthesis of elagolix have been depicted in figure 2 and 3.\nO\nOH\nN\nH\nN\nNO O\nF\nF F\nF\nO\nF\n4-[[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1-\nphenylethyl]amino]butanoic acid\nFigure 2: Structure of elagolix.\nFigure 3: Synthesis of elagolix sodium.\nF\nCN\nCF3\nReflux\nF\nCH2NH2\nCF3\nUrea, HCl\nReflux\nF\nCH2NH\nCF3\nO NH2\nNaI\nDiketene\nTMSCl\nHN\nN\nO\nO\nBr2\nAcOH\nHN\nN\nO\nO\nBr\nF\nF3C\nBH3, TF\nHO\nN\nH\nt-BOC\nPph3, DIAD,THF\nN\nN\nO\nHN\nt-BOC\nBr\nF\nF\nF\nF\nO\nB\nHO\nHO\nF O\nNa\n2CO3, \nPd(PPh\n3)4\nwater/ \ndioxide\nN\nN\nO\nO\nF\nO\nF\nF\nF\nF\nHNt-BOC\nTFA/DCM\nN\nN\nO\nO\nF\nO\nF\nF\nF\nF\nH2N\ni)Ethyl-4-bromobutyrate\nHuning's base ACN\nii)NaOH, THF/water Citric acid Dowax MSC-1\nN\nN\nO\nO\nF\nO\nF\nF\nF\nF\nHN\nO\nONa\nCitation: Paul J, Bhatia R (2021) Elagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis. J Clin Anesthes Res 2(1): pp. 1-6. doi:10.52916/jcar214007\n\nJ Clin Anesthes Res\nVolume 2 • Issue 1 • 7\n Page 4 of 6\nMode of action \n The Hypothalamus present in the forebrain and pituitary gland \nbelow it receives a signal from the peripheral nervous system and \nfunnels the signal into pituitary glands which control the other \nendocrine glands and our body responds to the environment. \nGnRH hormone releases in the hypothalamus and signals the \nanterior pituitary gland to release FSH and LH (Gonadotropins) \nthrough blood circulation this gonadotropin reaches the female \nreproductive system. Where LH triggers the theca cells and \nthrough biosynthesis produces estrone and oestradiol which are \nStructural Activity Relationship\n The benzyl group at position 1 (arm1) of the uracil core is essential. \nPosition 3 of uracil core is termed arm 2 along with butyrate \nmoiety (Figure 5). Phenyl group forms pie-pie interactions with \nN- terminus. Incorporation of butyrate moiety might increase \nthe solvent excess and water mediated interaction. Arm 3 at \nposition 5 of uracil core makes hydrophobic interactions with \nside chain of residues in N terminus of receptor. Methyl group \nat position 6 of Elagolix contribute to high affinity ligand binding \n[19]. \nthe first estrogens [18]. Estrogens produce the endometrial layer \nto support the egg in the uterus. Elagolix competitively acts on \nthe anterior pituitary receptor gland in place of GnRH and stops \nall the above processes of formation of the Gonadotropins and \nOestrogens. In this way, the production of estrogen reduces and \nthe formation of the endometrial layer decreases in and outside \nthe formation of the endometrial layer decreases in and outside \nthe uterus. When the release of estrogen release is suppressed\nthe condition is known as the hypoestrogenic condition. The \nmode of action of elagolix has been outlined in Figure 4.\nClinical trials (Application No: NCT01931670)\n The Phase 1 trials were initiated in February 2004. The phase 2 \ntrials were initiated in April 2005. Uterine leiomyoma associated \nendometriosis Phase 2 studies were initiated in September \n2013. Between 2012 to 2016 various studies were performed \nELARIS EM-IV, II, III and I.(clinical trials.org) [20]. In 2016 a \nglobal study was performed to evaluate the safety and efficacy \nof elagolix in subjects with moderate to severe endometriosis-\nassociated pain (ELARIS EM-II). The study consists of 815 \nparticipants having composite pelvic signs and symptoms score \nFigure 4: Mode of action of elagolix.\nCitation: Paul J, Bhatia R (2021) Elagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis. J Clin Anesthes Res 2(1): pp. 1-6. doi:10.52916/jcar214007\n\nJ Clin Anesthes Res\nVolume 2 • Issue 1 • 7\n Page 5 of 6\nof 6 or greater and dysmenorrhoea. The protocol of the \nclinical trial consists of 4 parts. 1) washout period, 2) screening \nperiod of up to 100 days before the first dose, 3) 6 months, \nand 4) a post-treatment follow-up period of up to 12 months \nand electronic diary to record responses. The subject using \nelagolix of doses 150mg and 200mg for 6 months. It was found \nthat there was a reduction of -0.85 or greater in the daily \nassessment of Dysmenorrhea (DYS) pain scale as well decreased \nin analgesic use for endometriosis-associated pain. And in the \nNon-menstrual pelvic pain scale, a reduction in -0.43 or greater \nwas recorded as well as no increased use of analgesics for \nendometriosis-associated pain [21]. At the end of 2016, the \npreregistration for endometriosis in the USA and priority review \nstatus was granted in the USA in October 2016. The prescription \ndrug user fee act (PDUFA) was extended to the third quarter of \nApril 2018. In July 2018 the Elagolix sodium was registered for \ntreatment for endometriosis in the USA. Still, Phase 3 clinical \ntrials are going on and will last in 2022.\nPharmacodynamics \n Elagolix is a highly potent non-peptide GnRH antagonist that \ncompetitively binds to GnRH receptors in the pituitary gland \nby blocking the endogenic GnRH signaling, elagolix dominates \nand decreases the Luteinizing Hormone (LH) and Follicle-\nStimulating Hormone (FSH), resulting in diminishing estradiol \nand progesterone production. Elagolix when administered \norally of doses 150 mg twice daily in a clinical trial in the healthy \nsubject it suppresses the LH, FSH, estradiol, and progesterone \nin a dose-dependent manner [22]. Women that participate in \nphase III trials having endometriosis dosed with 150 mg once \ndaily and 200 mg twice daily.\nPharmacokinetics \n Elagolix is dose-proportional in healthy premenopausal women \n(dose range 100-400 mg twice daily). It is rapidly absorbed with \nCmax reached within 1hour of the oral dose. Plasma protein \nbinding is 80%. Cmax reduces by 24 and 36% when elagolix is \nadministered orally with a high-fat content meal as compared \nto fasting. It belongs to BCS class III [23]. \nAdverse effects \n Elagolix sodium is the latest drug in the treatment of \nendometriosis. Nausea, headache, and nasopharyngitis are \nsome common side effects [24]. It overcomes the major side \neffects that occur by using drugs to treat this disease is Bone \nMineral Density (BMD)[25]. \nConclusion \n  Endometriosis is a non-cancerous uterine leiomyoma \ncharacterised by outgrown tissues in the endometrium layer \nthat arises in the innermost lining of the uterus, where cell \nproliferation results in the development of fibroids. We offered \na thorough description of pathogenesis and pathophysiology in \nthis study, with an emphasis on the experimental treatment of \nendometriosis with Elagolix Sodium, a recently approved GnRH \nantagonist. We included the synthesis, SAR, mode of action, \npharmacodynamics, pharmacokinetics, and clinical trials that \nwere conducted. The drug’s potential applications include \ntreating mild to serious uterine fibroids, as well as prostate \ncancer and other significant forms of cancer.\nReferences \n1. Hickey M, Ballard K, Farquhar C. Endometriosis. BMJ. \n2014;348(mar19 5):g1752.\n2. Zondervan KT, Becker CM, Koga K, et al. (2018) Endometriosis. \nNat Rev Dis Prim 4(1): pp. 9.\n3. Fourquet J, Gao X, Zavala D, et al. (2010) Patients’ report on \nhow endometriosis affects health, work, and daily life. Fertil \nSteril 93(7): pp. 2424-2428.\n4. endometriosis.org. Facts about endometriosis \n« Endometriosis.org. Published 2017. Accessed January 19, \n2021. http://endometriosis.org/resources/articles/facts-about-\nendometriosis/ \n5. Brown J, Tj C, Allen C,et al. (2017) Nonsteroidal anti-\ninflammatory drugs for pain in women with endometriosis \n(Cochrane Database Syst Rev 1(1): pp. CD004753. \n6. Gałczyński K, Jóźwik M, Lewkowicz D, et al. (2019) Ovarian \nendometrioma - A possible finding in adolescent girls and young \nwomen: A mini-review. J Ovarian Res 12(1): pp. 104. \n7. Marchand E, Hequet D, Thoury A, et al. (2013) Malignant \ntransformation of superficial peritoneal endometriosis lesion. \nBMJ Case Rep. 2013: pp. 7730.\n8. Kor E, Mostafavi SRS, Mazhin ZA, et al. (2020) Relationship \nbetween the severity of endometriosis symptoms (dyspareunia, \ndysmenorrhea and chronic pelvic pain) and the spread of the \ndisease on ultrasound. BMC Res Notes 13(1): pp. 1-8. \n9. Mori T, Ito F, Koshiba A, et al. (2018) Aromatase as a target for \ntreating endometriosis. J Obstet Gynaecol Res 44(9): pp. 1673-\n1681. \n10. Noble LS, Takayama K, Zeitoun KM, et al. (1997) Prostaglandin \nE 2 Stimulates Aromatase Expression in Endometriosis-Derived \nStromal Cells. J Clin Endocrinol Metab 82(2): pp. 600-606.\n11. Bulun SE, Yang S, Fang Z, et al. (2001) Role of aromatase \nin endometrial disease. J Steroid Biochem Mol Biol 79(1-5): pp. \n19-25.\n12. Bulun SE, Gurates B, Fang Z, et al. (2002) Mechanisms of\nFigure 5: Structural features of elagolix with respect to activity.\nO\nO\nN\nH\nN\nNO O\nF\nF F\nF\nO\nF\nArm2\nArm1\nArm3\nCore\nNa\nCitation: Paul J, Bhatia R (2021) Elagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis. J Clin Anesthes Res 2(1): pp. 1-6. doi:10.52916/jcar214007\n\nJ Clin Anesthes Res\nVolume 2 • Issue 1 • 7\n Page 6 of 6\nexcessive estrogen formation in endometriosis. J Reprod \nImmunol 55(1-2): pp. 21-33. \n13. Burney RO, Giudice LC (2012) Pathogenesis and \npathophysiology of endometriosis. Fertil Steril 98(3): pp. 511-\n519. \n14. Taylor HS, Dun EC, Chwalisz K (2019) Clinical evaluation of \nthe oral gonadotropin-releasing hormone-antagonist elagolix \nfor the management of endometriosis-associated pain. Pain \nManag 9(5): pp. 497-515.\n15. Giudice LC (2005) Endometriosis in Clinical Practice. N Engl J \nMed 362(25): pp. 2389-2398.\n16. Słopień R, Mȩczekalski B (2016) Aromatase inhibitors in the \ntreatment of endometriosis. Prz Menopauzalny 15(1): pp. 43-\n47.\n17. Lamb YN (2018) Elagolix: First Global Approval. Drugs 78(14): \npp. 1501-1508.\n18. Shebley M, Polepally AR, Nader A, et al. (2020) Clinical \nPharmacology of Elagolix: An Oral Gonadotropin-Releasing \nHormone Receptor Antagonist for Endometriosis. Clin \nPharmacokinet 59(3): pp. 297-309.\n19. Yan W, Cheng L, Wang W, et al. (2020) Structure of the human \ngonadotropin-releasing hormone receptor GnRH1R reveals an \nunusual ligand binding mode. Nat Commun 11(1): pp. 1-10.\n20. A Clinical Study to Evaluate the Safety and Efficacy of Elagolix \nin Subjects With Moderate to Severe Endometriosis-Associated \nPain - Full Text View - ClinicalTrials.gov. Accessed January 28, \n2021. https://www.clinicaltrials.gov/ct2/show/NCT01620528 \n21. NCT01931670. A Global Phase 3 Study to Evaluate the Safety \nand Efficacy of Elagolix in Subjects With Moderate to Severe \nEndometriosis-Associated Pain. Https://clinicaltrials.gov/show/\nnct01931670.\n22. Struthers RS, Nicholls AJ, Grundy J, et al. (2009) Suppression \nof gonadotropins and estradiol in premenopausal women by \noral administration of the nonpeptide gonadotropin-releasing \nhormone antagonist elagolix. J Clin Endocrinol Metab 94(2): pp. \n545-551.\n23. Winzenborg I, Nader A, Polepally AR, et al. (2018) Population \nPharmacokinetics of Elagolix in Healthy Women and Women \nwith Endometriosis. Clin Pharmacokinet 57(10): pp. 1295-1306.\n24. Surrey ES, Soliman AM, Agarwal SK, et al. (2019) Impact \nof elagolix treatment on fatigue experienced by women with \nmoderate to severe pain associated with endometriosis. Fertil \nSteril 112(2): pp. 298-304.\n25. Archer DF, Soliman AM, Agarwal SK, et al. (2020) Elagolix in \nthe treatment of endometriosis: impact beyond pain symptoms. \nTher Adv Reprod Heal 14.\nCitation: Paul J, Bhatia R (2021) Elagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis. J Clin Anesthes Res 2(1): pp. 1-6. doi:10.52916/jcar214007","source_license":"CC0","license_restricted":false}