Relugolix

{{Short description|Chemical compound}} {{Use dmy dates|date=March 2023}} {{Drugbox | Verifiedfields = | Watchedfields = | verifiedrevid = | image = Relugolix.svg | image_class = skin-invert-image | width = 250 | alt = | image2 = Relugolix molecule ball.png | image_class2 = bg-transparent | width2 = 250 | alt2 =

| pronounce = {{IPAc-en|ˌ|r|ɛ|l|ʊ|ˈ|g|oʊ|l|ɪ|k|s}} {{respell|RE|luu|GOH|liks}} | tradename = Orgovyx, Relumina | Drugs.com = {{drugs.com|monograph|relugolix}} | MedlinePlus = a621006 | DailyMedID = Relugolix | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category= | routes_of_administration = By mouth<ref name="pmid31461087" /> | class = GnRH antagonist | ATC_prefix = L02 | ATC_suffix = BX04 | ATC_supplemental = {{ATC|H01|CC54}} (combination with estradiol and norethisterone)

| legal_AU = S4 | legal_AU_comment = <ref>{{cite web | title=Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024 | website=Federal Register of Legislation | date=30 May 2024 | url=https://www.legislation.gov.au/F2024L00589/asmade/text | access-date=10 June 2024}}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Notice: Multiple additions to the Prescription Drug List (PDL) [2023-12-22] | website=Health Canada | date=22 December 2023 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/multiple-additions-2023-12-22.html | access-date=3 January 2024}}</ref><ref>{{cite web | title=Summary Basis of Decision (SBD) for Orgovyx | website=Health Canada | date=16 February 2024 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1708102173051 | access-date=24 February 2024}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Orgovyx FDA label">{{cite web | title=Orgovyx- relugolix tablet, film coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=077a92f6-9f1b-479a-87c7-c92b5db6aa9c | access-date=25 May 2021}}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Orgovyx EPAR" /> | legal_UN =  | legal_UN_comment = | legal_status =

| CAS_number_Ref = | CAS_number = 737789-87-6 | CAS_supplemental = | PubChem = 10348973 | IUPHAR_ligand = 5586 | DrugBank_Ref = | DrugBank = DB11853 | ChemSpiderID_Ref = | ChemSpiderID = 8524431 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = P76B05O5V6 | KEGG = D10888 | ChEBI = | ChEMBL = 1800159 | synonyms = RGX; RVT-601; TAK-385

| IUPAC_name = 1-[4-[1-[(2,6-difluorophenyl)methyl]-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl]phenyl]-3-methoxyurea | C=29 | H=27 | F=2 | N=7 | O=5 | S=1 | SMILES = CONC(=O)Nc1ccc(-c2sc3c(c2CN(C)C)c(=O)n(-c2ccc(OC)nn2)c(=O)n3Cc2c(F)cccc2F)cc1 | StdInChI = 1S/C29H27F2N7O5S/c1-36(2)14-19-24-26(39)38(22-12-13-23(42-3)34-33-22)29(41)37(15-18-20(30)6-5-7-21(18)31)27(24)44-25(19)16-8-10-17(11-9-16)32-28(40)35-43-4/h5-13H,14-15H2,1-4H3,(H2,32,35,40) | StdInChIKey = AOMXMOCNKJTRQP-UHFFFAOYSA-N }}

'''Relugolix''', sold under the brand names '''Orgovyx''' and '''Relumina''' among others, is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication which is used in the treatment of prostate cancer, uterine fibroids and endometriosis.<ref name="Orgovyx FDA label" /><ref name="pmid31461087">{{cite journal | vauthors = Barra F, Seca M, Della Corte L, Giampaolino P, Ferrero S | title = Relugolix for the treatment of uterine fibroids | journal = Drugs of Today | volume = 55 | issue = 8 | pages = 503–512 | date = August 2019 | pmid = 31461087 | doi = 10.1358/dot.2019.55.8.3020179 | s2cid = 201654739 }}</ref><ref name="ReluminaInfo">{{cite web | title = Relumina (relugolix) Information | work = ASKA Pharmaceutical | date = January 2019 | language = ja | access-date = 16 February 2019 | url = https://www.aska-pharma.co.jp/newitem/prd_relumina/data/info_new_relumina_1901_2.pdf| archive-url = https://web.archive.org/web/20190216153607/https://www.aska-pharma.co.jp/newitem/prd_relumina/data/info_new_relumina_1901_2.pdf | archive-date = 16 February 2019 }}</ref><ref name=":0">{{Cite news |title=New endometriosis pill approved on NHS in England |url=https://www.bbc.com/news/articles/cd7e47l3ny3o}}</ref> It is taken by mouth.<ref name="pmid31461087" /><ref name="ReluminaInfo" />

Side effects of relugolix include menstrual abnormalities, hot flashes, excessive sweating, headache, and decreased bone mineral density.<ref name="ReluminaInfo" /><ref name="pmid31461087" /> Relugolix is a GnRH antagonist, or an antagonist of the gonadotropin-releasing hormone receptor.<ref name="pmid31461087" /> Unlike most other GnRH modulators, but similarly to elagolix (brand name Orilissa), relugolix is a non-peptide, small-molecule compound and is orally active.<ref name="pmid21657270">{{cite journal |display-authors=6 |vauthors=Miwa K, Hitaka T, Imada T, Sasaki S, Yoshimatsu M, Kusaka M, Tanaka A, Nakata D, Furuya S, Endo S, Hamamura K, Kitazaki T |date=July 2011 |title=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 |journal=Journal of Medicinal Chemistry |volume=54 |issue=14 |pages=4998–5012 |doi=10.1021/jm200216q |pmid=21657270}}</ref><ref name="pmid24333551">{{cite journal |display-authors=6 |vauthors=Nakata D, Masaki T, Tanaka A, Yoshimatsu M, Akinaga Y, Asada M, Sasada R, Takeyama M, Miwa K, Watanabe T, Kusaka M |date=January 2014 |title=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 |journal=European Journal of Pharmacology |volume=723 |pages=167–174 |doi=10.1016/j.ejphar.2013.12.001 |pmid=24333551}}</ref><ref name="pmid29232843" /> It suppresses sex hormone levels to the postmenopausal or castrate range in both women and men.<ref name="pmid31461087" /><ref name="pmid26502357" /><ref name="Orgovyx FDA label" />

==Medical uses== Relugolix is approved in the United States, Canada and the United Kingdom for the treatment of prostate cancer, in Japan for the treatment of uterine fibroids (uterine leiomyoma) and in the United Kingdom for endometriosis.<ref name="AdisInsight">{{Cite web |title=Relugolix - Myovant/Takeda |url=http://adisinsight.springer.com/drugs/800028257 |work=AdisInsight |publisher=Springer Nature Switzerland AG}}</ref><ref name="ReluminaInfo" /><ref name="Orgovyx FDA label" /><ref name="PRNewswire2019" /><ref name=":0" />

===Available forms=== Relugolix is available in the form of 40 and 120 mg oral tablets.<ref name="Orgovyx FDA label" /><ref name="PRNewswire2019" /><ref name="ReluminaInfo" />

==Side effects== The main side effects of relugolix for uterine fibroids include abnormal uterine bleeding (24.6–48.6% vs. 6.3% for placebo), hot flashes (42.8–45.5% vs. 0% for placebo), heavy menstrual bleeding (12.1–49.3% vs. 9.4% for placebo), headache (12.3–15.2%), and excessive sweating (9.4–15.2% vs. 0% for placebo).<ref name="pmid31461087" /><ref name="ReluminaInfo" /> In addition, decreased bone mineral density occurs with relugolix (21.7% decrease by week 12, 24.4% decrease by week 24).<ref name="pmid31461087" />

==Pharmacology==

===Pharmacodynamics=== thumb|right|425px|class=skin-invert-image|Estradiol levels with 40 mg relugolix once per day in premenopausal women relative to untreated premenopausal women.<ref name="ReluminaInfo" />

Relugolix is a selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR), with a half-maximal inhibitory concentration (IC50) of 0.12 nM.<ref name="pmid31461087"/><ref name="pmid21657270" /><ref name="pmid24333551" />

A dosage of relugolix of 40 mg once per day has been found to suppress estradiol levels to postmenopausal levels (<20 pg/mL) within 24 hours in premenopausal women.<ref name="pmid31461087" /> In the control group of women, estradiol levels fluctuated between 50 and 250 pg/mL.<ref name="pmid31461087" /> Estradiol levels have been found to return to normal concentrations within 4 weeks of discontinuation of relugolix in premenopausal women.<ref name="pmid31461087" /> The medication additionally suppresses levels of progesterone, luteinizing hormone, and follicle-stimulating hormone in premenopausal women.<ref name="pmid31461087" /> Relugolix at a dosage of 40 mg or more once per day has been found to reduce testosterone levels to sustained castrate levels (<20 ng/dL) in men.<ref name="pmid26502357">{{cite journal | vauthors = MacLean DB, Shi H, Faessel HM, Saad F | title = Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 100 | issue = 12 | pages = 4579–4587 | date = December 2015 | pmid = 26502357 | pmc = 4667159 | doi = 10.1210/jc.2015-2770 }}</ref> It additionally suppresses luteinizing hormone and follicle-stimulating hormone levels in men.<ref name="pmid26502357" />

Lower doses of relugolix (<40 mg/day) are under investigation for achieving partial sex hormone suppression in the treatment of endometriosis and uterine fibroids.<ref name="pmid22439891">{{cite journal |vauthors=Streuli I, de Ziegler D, Borghese B, Santulli P, Batteux F, Chapron C |date=March 2012 |title=New treatment strategies and emerging drugs in endometriosis |journal=Expert Opinion on Emerging Drugs |volume=17 |pages=83–104 |doi=10.1517/14728214.2012.668885 |pmid=22439891 |s2cid=27472695}}</ref> This is intended to reduce the incidence and severity of menopausal symptoms such as hot flushes and decreased bone mineral density that are secondary to estrogen deficiency.<ref name="pmid22439891" /><ref name="pmid19033369">{{cite journal | vauthors = Struthers RS, Nicholls AJ, Grundy J, Chen T, Jimenez R, Yen SS, Bozigian HP | title = Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 94 | issue = 2 | pages = 545–551 | date = February 2009 | pmid = 19033369 | pmc = 2646513 | doi = 10.1210/jc.2008-1695 }}</ref>

===Pharmacokinetics=== A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL (47 nmol/L) after 1.5 hours.<ref name="pmid31461087" /> Steady-state levels are reached within 7 days with 40 mg/day relugolix administration.<ref name="pmid31461087" /> There is an approximate 2-fold accumulation of relugolix by 2 weeks of continuous administration.<ref name="pmid31461087" /> Food diminishes the oral bioavailability of relugolix by about 50%.<ref name="pmid31461087" />

Relugolix is a substrate for P-glycoprotein, which may have a limiting effect on its absorption and distribution.<ref name="pmid31461087" /> The plasma protein binding of relugolix is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL.<ref name="pmid31461087" />

Relugolix is not a substrate for CYP3A4.<ref name="pmid31461087" /> The elimination half-life of relugolix is 36 to 65 hours across a dosage range of 20 to 180 mg/day.<ref name="pmid31461087" /> There is moderate to high interindividual variability in systemic exposure to relugolix.<ref name="pmid31461087" />

Relugolix is excreted mainly in feces (83%) and to a small degree in urine (4%).<ref name="pmid31461087" /> Only about 6% of a dose of relugolix is excreted unchanged.<ref name="pmid31461087" />

==Chemistry== Relugolix is a non-peptide, small-molecule compound, and is structurally distinct from GnRH analogues.<ref name="pmid29232843">{{cite journal | vauthors = Tukun FL, Olberg DE, Riss PJ, Haraldsen I, Kaass A, Klaveness J | title = Recent Development of Non-Peptide GnRH Antagonists | journal = Molecules | volume = 22 | issue = 12 | page = 2188 | date = December 2017 | pmid = 29232843 | pmc = 6149776 | doi = 10.3390/molecules22122188 | doi-access = free }}</ref> It is an ''N''-phenyl urea derivative.<ref name="pmid31461087" />

===Synthesis=== The discovery route of relugolix was recently reported:<ref>{{cite journal | vauthors=((Flick, A. C.)), ((Leverett, C. A.)), ((Ding, H. X.)), ((McInturff, E.)), ((Fink, S. J.)), ((Mahapatra, S.)), ((Carney, D. W.)), ((Lindsey, E. A.)), ((DeForest, J. C.)), ((France, S. P.)), ((Berritt, S.)), ((Bigi-Botterill, S. V.)), ((Gibson, T. S.)), ((Liu, Y.)), ((O'Donnell, C. J.)) | journal=Journal of Medicinal Chemistry | title=Synthetic Approaches to the New Drugs Approved during 2019 | volume=64 | issue=7 | pages=3604–3657 | date=8 April 2021 | url=https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00208 | doi=10.1021/acs.jmedchem.1c00208}}</ref> A scalable process was also developed recently:<ref>{{cite journal | vauthors=((Wang, X.)), ((Luo, Y.)), ((Zhang, P.)), ((Zhu, X.)), ((Liu, X.)), ((Chen, Y.)) | journal=Tetrahedron | title=An alternative and scalable synthesis for Relugolix | volume=167 | article-number=134243 | date= November 2024 | url=https://linkinghub.elsevier.com/retrieve/pii/S004040202400423X | doi=10.1016/j.tet.2024.134243| url-access=subscription }}</ref> invert-skin-image|700px|center A Gewald aminothiophene synthesis between 4-nitrophenylacetone [5332-96-7] ('''1''') and ethyl cyanoacetate [105-56-6] ('''2''') in the presence of sulfur and triethylamine to give an aminothiophene [174072-89-0]. The amino group was protected with cathyl chloride to give the corresponding carbamate, [308831-93-8] ('''3'''). Alkylation with 2,6-Difluorobenzyl chloride [697-73-4] ('''4''') gave [308831-94-9]. Next, a free-radical bromination gave [308831-95-0] ('''5'''). Displacement of the bromide with (2-methoxyethyl)(methyl)amine [38256-93-8] ('''6''') and subsequent catalytic hydrogenation of the nitro group gave PC53388810 ('''7'''). The aniline was reacted with CDI, and the resulting imidazolide was further treated with methoxyamine [67-62-9] to give the urea [737789-92-3] ('''8'''). A cyclization reaction mediated by diethyl pyrocarbonate (DEPC) in the presence of 3-methoxy-6-aminopyridazine [7252-84-8] ('''9''') followed by exposure to sodium methoxide generated thymine derivative [737789-61-6] ('''10'''). Quaternization of the basic amine with 1-chloroethyl chloroformate followed by displacement with dimethylamine completed the synthesis of relugolix ('''11''').

==History== Relugolix was first described in 2004.<ref name="US7300935">{{Cite patent | country = US | number = 7300935 | url=https://patents.google.com/patent/US7300935 |title = Thienopyrimidine compounds and use thereof | inventor = Cho N, Imada T, Hitaka T, Miwa K, Kusaka M, Suzuki N | assign1 = Takeda Pharmaceutical Co Ltd | gdate = 27 November 2007 | postscript = . }}</ref><ref name="pmid21657270" /> It superseded sufugolix (developmental code name TAK-013), which was developed by the same researchers.<ref name="pmid21657270" /> Relugolix was approved for the treatment of uterine fibroids in Japan in January 2019.<ref name="AdisInsight" /><ref name="PRNewswire2019" /> It was the second orally active GnRH antagonist to be introduced for medical use, following elagolix (brand name Orilissa) in July 2018.<ref name="AdisInsight" /><ref name="AdisInsight-Elagolix">{{Cite web | url=https://adisinsight.springer.com/drugs/800020238 | title=Elagolix - Abbvie/Neurocrine Biosciences | work = AdisInsight | publisher = Springer Nature Switzerland AG }}</ref> Relugolix was approved for the treatment of prostate cancer in the United States on 18 December 2020.<ref name="AdisInsight" /><ref name="Orgovyx FDA label" />

The FDA approved relugolix based on evidence from a clinical trial (NCT03085095) of 930 participants 48 to 97 years old with advanced prostate cancer.<ref name="FDA snapshot" /> The trial was conducted at 155 sites in the United States, Canada, and countries in South America, Europe and the Asia Pacific region.<ref name="FDA snapshot" /> All participants in the trial had advanced prostate cancer.<ref name="FDA snapshot" /> Participants were randomly assigned to receive either one relugolix tablet daily (on the first day they received three tables) or an active control (leuprolide acetate) which was given as an injection under the skin every three months.<ref name="FDA snapshot" /> The participants and healthcare providers were aware of which treatment was being given.<ref name="FDA snapshot" /> The treatment lasted for 48 weeks.<ref name="FDA snapshot" /> The efficacy of relugolix was assessed by the percentage of participants who achieved and maintained low testosterone level equal to castration.<ref name="FDA snapshot">{{cite web | title=Drug Trial Snapshot: Orgovyx | website=U.S. Food and Drug Administration (FDA) | date=18 December 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-orgovyx | access-date=6 January 2021}} {{PD-notice}}</ref>

==Society and culture== === Names === ''Relugolix'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="ChemIDplus">{{Cite web | url=https://pubchem.ncbi.nlm.nih.gov/#tab/sidsrcname=ChemIDplus&query=737789-87-6&input_type=text | work = ChemIDplus | publisher = U.S. National Library of Medicine | title = Relugolix }}</ref><ref name="KEGG">{{Cite web | url=https://www.kegg.jp/entry/D10888 | work = KEGG DRUG Database | publisher = Kyoto Encyclopedia of Genes and Genomes | title = Relugolix}}</ref> It is also known by its former developmental code names RVT-601 and TAK-385.<ref name="AdisInsight" /><ref name="ChemIDplus" />

Relugolix is sold under the brand name Orgovyx for the treatment of prostate cancer and under the brand name Relumina for the treatment of uterine fibroids.<ref name="AdisInsight" /><ref name="PRNewswire2019">{{Cite press release | url=https://www.prnewswire.com/news-releases/myovant-provides-corporate-updates-and-reports-financial-results-for-third-fiscal-quarter-ended-december-31-2018-300791994.html | title=Myovant Provides Corporate Updates and Reports Financial Results for Third Fiscal Quarter Ended December 31, 2018}}</ref><ref name="ReluminaInfo" /><ref name="Orgovyx FDA label" /> Relugolix compounded with estradiol hemihydrate and norethindrone is sold under the brand name Myfembree for the treatment of uterine fibroids.<ref>{{cite web | title=Myfembree- relugolix, estradiol hemihydrate, and norethindrone acetate tablet, film coated | website=DailyMed | date=18 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc3feb73-cc84-43a8-aa32-b262460495e8 | access-date=24 February 2024}}</ref>

=== Legal status === In February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Orgovyx, intended for the treatment of prostate cancer.<ref name="Orgovyx: Pending EC decision" /> The applicant for this medicinal product is Myovant Sciences Ireland Limited.<ref name="Orgovyx: Pending EC decision">{{cite web | title=Orgovyx: Pending EC decision | website=European Medicines Agency | date=24 February 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/orgovyx | access-date=27 February 2022 | archive-date=27 February 2022 | archive-url=https://web.archive.org/web/20220227000205/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/orgovyx }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Relugolix was approved for medical use in the European Union in April 2022,<ref name="Orgovyx EPAR">{{cite web | title=Orgovyx EPAR | website=European Medicines Agency | date=22 February 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/orgovyx | access-date=3 March 2023}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=Orgovyx Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1642.htm | access-date=3 March 2023}}</ref> and in the United Kingdom in July 2022<ref>{{cite web | title=ORGOVYX FILM-COATED TABLETS RELUGOLIX - PLGB 00142/1272 | url=https://products.mhra.gov.uk/product/?product=ORGOVYX | access-date=20 September 2024 }}</ref> (although not available in NHS England until August 2024<ref>{{cite web | title=Relugolix for treating hormone-sensitive prostate cancer | url=https://www.nice.org.uk/guidance/TA995 | access-date=20 September 2024 }}</ref>).

== References == {{Reflist}}

== Further reading == {{refbegin}} * {{cite journal | vauthors = Markham A | title = Relugolix: First Global Approval | journal = Drugs | volume = 79 | issue = 6 | pages = 675–679 | date = April 2019 | pmid = 30937733 | doi = 10.1007/s40265-019-01105-0 | s2cid = 89616869 }} * {{cite journal| vauthors = Elsharoud A, Ali M, Al-Hendy A |title=Relugolix. GnRH (LHRH) receptor antagonist, Treatment of uterine fibroids, Treatment of endometriosis-related pain, Treatment of prostate cancer|journal=Drugs of the Future|volume=44|issue=2|year=2019|page=131|issn=0377-8282|doi=10.1358/dof.2019.44.2.2927590|s2cid=87369995}} * {{cite journal | vauthors = Barra F, Seca M, Della Corte L, Giampaolino P, Ferrero S | title = Relugolix for the treatment of uterine fibroids | journal = Drugs of Today | volume = 55 | issue = 8 | pages = 503–512 | date = August 2019 | pmid = 31461087 | doi = 10.1358/dot.2019.55.8.3020179 | s2cid = 201654739 }} {{refend}}

== External links == * {{ClinicalTrialsGov|NCT03085095|A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer (HERO)}}

{{Pituitary and hypothalamic hormones and analogues}} {{GnRH and gonadotropins}} {{GnRH and gonadotropin receptor modulators}} {{Portal bar | Medicine}}

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