Relugolix/Estradiol/Norethisterone Acetate: A Review in Endometriosis-Associated Pain

Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;379: e070750.

Article  PubMed  Google Scholar 

Lamceva J, Uljanovs R, Strumfa I. The main theories on the pathogenesis of endometriosis. Int J Mol Sci. 2023;24(5):4254.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chantalat E, Valera MC, Vaysse C, et al. Estrogen receptors and endometriosis. Int J Mol Sci. 2020;21(8):2815.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arjona Ferreira JC, Migoya E. Development of relugolix combination therapy as a medical treatment option for women with uterine fibroids or endometriosis. Fertil Steril Rep. 2023;4(2S):73–82.

Google Scholar 

Barbara G, Buggio L, Facchin F, et al. Medical treatment for endometriosis: tolerability, quality of life and adherence. Front Glob Womens Health. 2021;2: 729601.

Article  PubMed  PubMed Central  Google Scholar 

Myovant Sciences Inc. MYFEMBREE® (relugolix, estradiol, and norethindrone acetate) tablets, for oral use: US prescribing information. 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc3feb73-cc84-43a8-aa32-b262460495e8. Accessed 28 Feb 2024.

Gedeon Richter Plc. Ryeqo (relugolix/estradiol/norethisterone acetate) 40 mg/1 mg/0.5 mg film-coated tablets: EU summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/ryeqo-epar-product-information_en.pdf. Accessed 28 Feb 2024.

Syed YY. Relugolix/estradiol/norethisterone (norethindrone) acetate: a review in symptomatic uterine fibroids. Drugs. 2022;82(15):1549–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Giudice LC, As-Sanie S, Arjona Ferreira JC, et al. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet. 2022;399(10343):2267–79.

Article  CAS  PubMed  Google Scholar 

Osuga Y, Seki Y, Tanimoto M, et al. Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study. Fertil Steril. 2021;115(2):397–405.

Article  CAS  PubMed  Google Scholar 

Osuga Y, Seki Y, Tanimoto M, et al. Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, in women with endometriosis-associated pain: phase 2 safety and efficacy 24-week results. BMC Womens Health. 2021;21(1):250.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Venturella R, As-Sanie S, Kotarski J, et al. Effects of relugolix combination therapy on endometriosis-associated pain and analgesic use in spirit studies: overall study and European populations [abstract no. 70]. Eur J Obstet Gynecol Reprod Biol. 2022;270:e32–3.

Google Scholar 

As-Sanie S, Brown EL, Imm SJ, et al. Relugolix combination therapy in North American women with endometriosis-associated pain: SPIRIT 1 and 2 trials [abstract no. P-271]. Fertil Steril. 2022;118(4):e223.

Article  Google Scholar 

Becker C, Kotarski J, Mehedintu C, et al. The effect of time since surgical diagnosis of endometriosis on treatment outcomes with relugolix combination therapy in women with endometriosis-associated pain: SPIRIT program [abstract no. O-131]. Hum Repod. 2021;36(Suppl 1):i57.

Google Scholar 

As-Sanie S, Mathur V, Mehedintu C, et al. Relugolix combination therapy improves multiple dimensions of quality of life in women with endometriosis-associated pain: results from the SPIRIT program [abstract no. O-118]. Fertil Steril. 2021;116(3 Suppl):e51.

Article  Google Scholar 

Becker CM, Johnson NP, As-Sanie S, et al. Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. Hum Reprod. 2024;39(3):526–37.

Article  PubMed  PubMed Central  Google Scholar 

As-Sanie S, Johnson N, Lukes AS, et al. Time to minimal or no pelvic pain with relugolix combination therapy in women with endometriosis-associated pain: results from the SPIRIT program [abstract no. 0–14]. Fertil Steril. 2022;118(4 Suppl):e6-7.

Article  Google Scholar 

Lukes AS, As-Sanie S, Becker CM, et al. Bleeding patterns in women with endometriosis-associated pain treated with relugolix combination therapy: SPIRIT program [abstract no. O-017]. Reprod Sci. 2021;28(Suppl 1):55A.

Google Scholar 

As-Sanie S, Giudice L, Jung S, et al. Bleeding patterns with relugolix combination therapy in women with endometriosis-associated pain [abstract no. 1345374]. Obstet Gynecol. 2023;141(5 Suppl):12S.

Article  CAS  Google Scholar 

As-Sanie S, Mehedintu C, Mathur V, et al. Sustained improvement in physical function and quality of life in women with endometriosis-associated pain treated with relugolix combination therapy over 104 weeks: SPIRIT long-term extension study [abstract no. O-1]. Fertil Steril. 2022;118(4 Suppl):e1.

Article  Google Scholar 

McClung MR, Santora A, Johnson N, et al. Relugolix combination therapy minimizes bone loss in patients with endometriosis-associated pain: results from the phase 3 SPIRIT program [abstract no. VPP-520]. J Bone Miner Res. 2022;37(Suppl 1):109.

Google Scholar 

Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):1–26.

Article  Google Scholar 

AbbVie Inc. ORILISSA® (elagolix) tablets, for oral use: US prescribing information. 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a86757b3-09c5-fd3b-1223-244e94f50a66. Accessed 28 Feb 2024.

Chapron C, Marcellin L, Borghese B, et al. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol. 2019;15(11):666–82.

Article  PubMed  Google Scholar 

Whitaker LHR, Saraswat L, Horne AW. Combination GnRH antagonists for endometriosis: balancing efficacy with side effects. Cell Rep Med. 2022;3(9): 100748.

Article  CAS  PubMed  PubMed Central  Google Scholar 

US National Institutes of Health. ClinicalTrials identifier NCT05862272. 2023. https://clinicaltrials.gov. Accessed 28 Feb 2024.

Miwa K, Hitaka T, Imada T, et al. Discovery of 1-4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor. J Med Chem. 2011;54(14):4998–5012.

Article  CAS  PubMed  Google Scholar 

Nakata D, Masaki T, Tanaka A, et al. Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice. Eur J Pharmacol. 2014;723:167–74.

Article  CAS  PubMed  Google Scholar 

Lukes A, Johnson B, Jones L, et al. Pharmacokinetics, pharmacodynamics, and safety of relugolix, a potent oral once-daily gonadotropin-releasing hormone (GnRH) receptor antagonist, as monotherapy and in combination with estradiol/norethindrone acetate add-back therapy [abstract no. P-287]. Hum Reprod. 2017;32(Suppl 1):i267–8.

Google Scholar 

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