Nafarelin

{{Short description|Pharmaceutical drug}} {{Drugbox | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 462258124 | IUPAC_name = (2''R'')-''N''-[(2''R'')-5-carbamimidamido-1-[(2''S'')-2-[(carbamoylmethyl)carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]-2-[(2''R'')-2-[(2''R'')-2-[(2''R'')-3-hydroxy-2-[(2''S'')-2-[(2''S'')-3-(1''H''-imidazol-4-yl)-2-<nowiki/>{[(2''R'')-5-oxopyrrolidin-2-yl]formamido}propanamido]-3-(1''H''-indol-3-yl)propanamido]propanamido]-3-(4-hydroxyphenyl)propanamido]-3-(naphthalen-2-yl)propanamido]-4-methylpentanamide | image = Nafarelin.svg | image_class = skin-invert-image | width = 250px

| tradename = Synarel, Nasanyl, others | Drugs.com = {{drugs.com|monograph|synarel}} | MedlinePlus = a601082 | pregnancy_category = X | legal_status = Rx-only | routes_of_administration = Nasal spray<ref name="pmid2140979" /><ref name="SynarelLabel" /> | class = GnRH analogue; GnRH agonist; Antigonadotropin

| bioavailability = {{abbrlink|IN|Intranasal administration}}: 2.8% (1.2–5.6%)<ref name="SynarelLabel" /> | protein_bound = 80%<ref name="SynarelLabel" /> | metabolism = Peptidases (not {{abbrlink|CYP450|cytochrome P450}})<ref name="SynarelLabel" /> | elimination_half-life = {{abbr|IN|Intranasal administration}}: 2.5–3.0 hours<ref name="SynarelLabel" /> {{Font|size=98%|{{abbrlink|SC|Subcutaneous injection}}: 86 hours (metabolites)<ref name="SynarelLabel" />}} | excretion = Urine: 44–55%<ref name="SynarelLabel" /> Feces: 19–44%<ref name="SynarelLabel" />

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 76932-56-4 | CAS_supplemental = 76932-60-0 (acetate) | ATC_prefix = H01 | ATC_suffix = CA02 | PubChem = 25077649 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00666 | IUPHAR_ligand = 3902 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 10482014 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 1X0094V6JV | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 7445 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1201309 | KEGG = D08241 | synonyms = Nafareline; Nafarelin acetate; RS-94991; RS-94991-298; [6-D-(2-naphthyl)alanine]-GnRH

| C=66 | H=83 | N=17 | O=13 | SMILES = CC(C)C[C@H](NC(=O)[C@@H](Cc1ccc2ccccc2c1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)NCC(N)=O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C66H83N17O13/c1-36(2)25-48(58(89)76-47(13-7-23-71-66(68)69)65(96)83-24-8-14-54(83)64(95)73-33-55(67)86)77-60(91)50(28-38-15-18-39-9-3-4-10-40(39)26-38)78-59(90)49(27-37-16-19-43(85)20-17-37)79-63(94)53(34-84)82-61(92)51(29-41-31-72-45-12-6-5-11-44(41)45)80-62(93)52(30-42-32-70-35-74-42)81-57(88)46-21-22-56(87)75-46/h3-6,9-12,15-20,26,31-32,35-36,46-54,72,84-85H,7-8,13-14,21-25,27-30,33-34H2,1-2H3,(H2,67,86)(H,70,74)(H,73,95)(H,75,87)(H,76,89)(H,77,91)(H,78,90)(H,79,94)(H,80,93)(H,81,88)(H,82,92)(H4,68,69,71)/t46-,47-,48-,49-,50+,51-,52-,53-,54-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = RWHUEXWOYVBUCI-ITQXDASVSA-N }}  '''Nafarelin''', sold under the brand name '''Synarel''' among others, is a gonadotropin-releasing hormone agonist (GnRH agonist) medication which is used in the treatment of endometriosis and early puberty.<ref name="pmid2140979">{{cite journal | vauthors = Chrisp P, Goa KL | title = Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions | journal = Drugs | volume = 39 | issue = 4 | pages = 523–551 | date = April 1990 | pmid = 2140979 | doi = 10.2165/00003495-199039040-00005 }}</ref><ref name="SynarelLabel">{{cite web |title=Synarel® (nafarelin acetate) nasal solution |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019886s033s035lbl.pdf |access-date=10 July 2024 |archive-date=3 January 2020 |archive-url=https://web.archive.org/web/20200103181633/https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019886s033s035lbl.pdf |url-status=dead }}</ref> It is also used to treat uterine fibroids, to control ovarian stimulation in ''in vitro'' fertilization (IVF), and as part of transgender hormone therapy.<ref name="pmid10900582">{{cite journal | vauthors = Minaguchi H, Wong JM, Snabes MC | title = Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature | journal = The Journal of Reproductive Medicine | volume = 45 | issue = 6 | pages = 481–489 | date = June 2000 | pmid = 10900582 }}</ref><ref name="Mutschler2001" /><ref name="pmid27241976" /><ref name="pmid23385274" /> The medication is used as a nasal spray two to three times per day.<ref name="pmid2140979" /><ref name="SynarelLabel" /><ref name="pmid22028996">{{cite journal | vauthors = Magon N | title = Gonadotropin releasing hormone agonists: Expanding vistas | journal = Indian Journal of Endocrinology and Metabolism | volume = 15 | issue = 4 | pages = 261–267 | date = October 2011 | pmid = 22028996 | pmc = 3193774 | doi = 10.4103/2230-8210.85575 | doi-access = free }}</ref>

Side effects of nafarelin are related to sex hormone deprivation and include symptoms of low testosterone levels and low estrogen levels such as hot flashes, sexual dysfunction, vaginal atrophy, and osteoporosis.<ref name="SynarelLabel" /> Nafarelin is a gonadotropin-releasing hormone agonist (GnRH agonist) and works by preventing the production of sex hormones by the gonads.<ref name="pmid2140979" /><ref name="SynarelLabel" /> It can lower sex hormone levels by 95% in both sexes.<ref name="pmid2140979" /><ref name="SynarelLabel" /> Nafarelin is a peptide and an analogue of {{abbrlink|GnRH|gonadotropin-releasing hormone}}.<ref name="Srivastava2017">{{cite book| vauthors = Srivastava V |title=Peptide-based Drug Discovery: Challenges and New Therapeutics|url=https://books.google.com/books?id=sbcpDwAAQBAJ&pg=PA182|date=26 June 2017|publisher=Royal Society of Chemistry|isbn=978-1-78262-732-6|pages=182–}}</ref>

Nafarelin was introduced for medical use in 1990.<ref name="Drugs@FDA" /><ref name="pmid2140979" /><ref name="pmid1984190" /> It is available widely throughout the world, including in North America, Europe, and elsewhere throughout the world.<ref name="Drugs.com" /><ref name="IndexNominum2000" /> The medication is one of only two medically used GnRH analogues that are available as nasal sprays, the other being buserelin.<ref name="Önerci2013">{{cite book|vauthors=Önerci TM|title=Nasal Physiology and Pathophysiology of Nasal Disorders|url=https://books.google.com/books?id=qfu8BAAAQBAJ&pg=PA208|date=17 August 2013|publisher=Springer Science & Business Media|isbn=978-3-642-37250-6|pages=208–|access-date=10 July 2024|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020305/https://books.google.com/books?id=qfu8BAAAQBAJ&pg=PA208|url-status=live}}</ref>

==Medical uses== Nafarelin is approved and used in the treatment of endometriosis and precocious puberty.<ref name="SynarelLabel" /><ref name="pmid2140979" /> It is also used in the treatment of uterine fibroids.<ref name="pmid10900582" /><ref name="pmid2533618">{{cite journal | vauthors = Monroe SE, Andreyko J | title = Treatment of uterine leiomyomas and hirsutism with nafarelin | journal = The Journal of Reproductive Medicine | volume = 34 | issue = 12 Suppl | pages = 1029–1033 | date = December 1989 | pmid = 2533618 }}</ref> The medication is used to control ovarian stimulation in ''in vitro'' fertilization (IVF).<ref name="Mutschler2001">{{Cite book| vauthors = Mutschler E, Schäfer-Korting M |title=Arzneimittelwirkungen|language=de|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2001|edition=8|pages=372–3|isbn=3-8047-1763-2}}</ref><ref>{{cite journal | vauthors = Wuttke W, Jarry H, Feleder C, Moguilevsky J, Leonhardt S, Seong JY, Kim K | title = The neurochemistry of the GnRH pulse generator | journal = Acta Neurobiologiae Experimentalis | volume = 56 | issue = 3 | pages = 707–713 | year = 1996 | doi = 10.55782/ane-1996-1176 | pmid = 8917899 | url = http://www.ane.pl/linkout.php?vol=56&no=3&fpp=707 | access-date = 2015-11-27 | archive-date = 2015-12-08 | archive-url = https://web.archive.org/web/20151208053059/http://www.ane.pl/linkout.php?vol=56&no=3&fpp=707 | url-status = dead | doi-access = free }}</ref> Nafarelin is used as a puberty blocker in transgender youth and to suppress testosterone levels in transgender women.<ref name="LeePerl2018">{{cite book| vauthors = Lee JY, Perl L, Rosenthal SM |title=Pediatric Endocrinology |chapter=Care of Gender Nonconforming/Transgender Youth |year=2018|pages=813–823|publisher=Springer |doi=10.1007/978-3-319-73782-9_36|isbn=978-3-319-73781-2}}</ref><ref name="pmid27241976">{{cite journal | vauthors = Olshan J, Eimicke T, Belfort E | title = Gender Incongruity in Children With and Without Disorders of Sexual Differentiation | journal = Endocrinology and Metabolism Clinics of North America | volume = 45 | issue = 2 | pages = 463–482 | date = June 2016 | pmid = 27241976 | doi = 10.1016/j.ecl.2016.02.001 }}</ref><ref name="pmid24972421">{{cite journal | vauthors = Olson J, Garofalo R | title = The peripubertal gender-dysphoric child: puberty suppression and treatment paradigms | journal = Pediatric Annals | volume = 43 | issue = 6 | pages = e132–e137 | date = June 2014 | pmid = 24972421 | doi = 10.3928/00904481-20140522-08 }}</ref><ref name="pmid23385274">{{cite journal | vauthors = Spack NP | title = Management of transgenderism | journal = JAMA | volume = 309 | issue = 5 | pages = 478–484 | date = February 2013 | pmid = 23385274 | doi = 10.1001/jama.2012.165234 }}</ref><ref name="Nakatsuka2014">{{cite journal | vauthors = Nakatsuka M | title = Endocrine treatment of transsexuals: assessment of cardiovascular risk factors | journal = Expert Review of Endocrinology & Metabolism | volume = 5 | issue = 3 | pages = 319–322 | date = May 2010 | pmid = 30861686 | doi = 10.1586/eem.10.18 | s2cid = 73253356 | doi-access = free }}</ref> Nafarelin can also be used to treat hirsutism and polycystic ovary syndrome by lowering gonadotropin and androgen levels.<ref name="pmid2140979" /><ref name="pmid2533618" /><ref name="pmid2969835">{{cite journal | vauthors = Shaw RW | title = GnRH agonists-antagonists--clinical applications | journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology | volume = 28 | issue = 2 | pages = 109–116 | date = June 1988 | pmid = 2969835 | doi = 10.1016/0028-2243(88)90086-X | doi-access = free }}</ref> It is effective in the treatment of benign prostatic hyperplasia.<ref name="pmid2140979" />

===Dosages=== Nafarelin is used to treat precocious puberty at a dosage of 1,600 to 1,800 μg per day.<ref name="SynarelLabel" /> The 1,600 μg/day dosage is achieved by two sprays (400 μg total) into each nostril in the morning (four sprays, 800 μg total) and two sprays (400 μg total) into each nostril in the evening (four sprays, 800 μg total).<ref name="SynarelLabel" /> If 1,600 μg/day is insufficient for adequate pubertal suppression, the 1,800 μg/day dosage can be used instead. This is achieved by three sprays (600 μg total) into alternating nostrils three times per day (nine sprays per day total).<ref name="SynarelLabel" /> When administering the sprays, the head should be tilted back slightly and 30 seconds should elapse between each spray.<ref name="SynarelLabel" /> A bottle of nafarelin nasal spray (brand name Synarel) lasts for about 7 days at a dosage of 1,600 μg/day.<ref name="SynarelLabel" />

Nafarelin is used to treat endometriosis at lower dosages of 400 to 800 μg per day.<ref name="SynarelLabel" /> This is achieved by one or two sprays (200 or 400 μg total) into alternating nostrils once in the morning and once in the evening (two to four sprays per day total).<ref name="SynarelLabel" /> A bottle of nafarelin nasal spray (brand name Synarel) lasts for about 30 days at a dosage of 400 μg/day.<ref name="SynarelLabel" />

===Available forms=== Nafarelin is available in the form of a 0.2% nasal spray for use one, two, or three times per day.<ref name="LemkeWilliams2012">{{cite book|vauthors=Lemke TL, Williams DA|title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA230|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=230–|access-date=10 July 2024|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020305/https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA230|url-status=live}}</ref><ref name="SynarelLabel" /><ref name="pmid2140979" /> Each bottle of nafarelin nasal spray (brand name Synarel) contains about 60 sprays delivering approximately 200 μg nafarelin in 100 μL solution per actuation.<ref name="SynarelLabel" /> Nafarelin is not available for use by any other routes than intranasal administration.<ref name="FalconeHurd2017" />

==Side effects== Side effects of nafarelin are related to sex hormone deficiency and include hot flashes, vaginal dryness, headaches, mood changes, and sexual dysfunction. Nafarelin causes erectile dysfunction in more than half of men with benign prostatic hyperplasia treated with it.<ref name="MunarrizTraish2009">{{cite book| vauthors = Munarriz R, Traish A |title=Sexual Function in the Prostate Cancer Patient|chapter=Impact of Androgen Deprivation on Male Sexual Function|year=2009|pages=163–175|publisher=Humana Press |doi=10.1007/978-1-60327-555-2_11|isbn=978-1-60327-554-5}}</ref> Some people may experience acne, muscle pain, reduced breast size, and nasal irritation. These side effects are reversible and should resolve after stopping the medication.<ref>DailyMed: [https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d0aa57cb-d2f4-46d7-af43-7c8b06aa81a6 Synarel – nafarelin acetate spray] </ref> There is a case report of severe hyperkalemia during nafarelin therapy in a woman with uterine fibroids.<ref name="pmid8569395">{{cite journal | vauthors = Hata T, Hata K, Kawamura T | title = Severe hyperkalaemia with nafarelin | journal = Lancet | volume = 347 | issue = 8997 | pages = 333 | date = February 1996 | pmid = 8569395 | doi = 10.1016/S0140-6736(96)90514-0 | s2cid = 39987508 | doi-access = free }}</ref> The mechanism is unknown.<ref name="pmid8569395" />

==Pharmacology==

===Pharmacodynamics=== Nafarelin is a GnRH agonist, or an agonist of the GnRH receptor, the biological target of GnRH.<ref name="pmid2140979" /><ref name="SynarelLabel" /> It works by continuously activating the GnRH receptor, which results in profound desensitization of the receptor such that it becomes non-functional.<ref name="pmid2140979" /><ref name="SynarelLabel" /> As a result, nafarelin suppresses the GnRH-induced secretion of the gonadotropins, luteinizing hormone and follicle-stimulating hormone, from the pituitary gland.<ref name="pmid2140979" /><ref name="SynarelLabel" /> This, in turn, results in profound suppression of gonadal sex hormone production, as well as reversible suppression of fertility.<ref name="pmid2140979" /><ref name="SynarelLabel" />

===Pharmacokinetics=== The bioavailability of nafarelin with intranasal administration is 2.8% on average, with a range of 1.2 to 5.6%.<ref name="SynarelLabel" /> The plasma protein binding of nafarelin is 80%.<ref name="SynarelLabel" /> It is metabolized primarily by peptidases and not by cytochrome P450 enzymes.<ref name="SynarelLabel" /> The elimination half-life of nafarelin is 2.5 to 3.0 hours by intranasal administration, whereas the half-life of nafarelin and its metabolites by subcutaneous injection is 85.5 hours.<ref name="SynarelLabel" /> Nafarelin is eliminated 44 to 55% in urine and 18.5 to 44.2% in feces.<ref name="SynarelLabel" />

==Chemistry== Nafarelin is a GnRH analogue, or a synthetic analogue of GnRH.<ref name="pmid2140979" /><ref name="SynarelLabel" /><ref name="FalconeHurd2017" /> It is a decapeptide and is also known as [6-D-(2-naphthyl)alanine]-GnRH.<ref name="FalconeHurd2017">{{cite book|vauthors=Falcone T, Hurd WW|title=Clinical Reproductive Medicine and Surgery: A Practical Guide|url=https://books.google.com/books?id=pzgoDwAAQBAJ&pg=PA9|date=14 June 2017|publisher=Springer|isbn=978-3-319-52210-4|pages=9–|access-date=10 July 2024|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020331/https://books.google.com/books?id=pzgoDwAAQBAJ&pg=PA9|url-status=live}}</ref><ref name="pmid8477775">{{cite journal | vauthors = Kreuser ED, Klingmüller D, Thiel E | title = The role of LHRH-analogues in protecting gonadal functions during chemotherapy and irradiation | journal = European Urology | volume = 23 | issue = 1 | pages = 157–63; discussion 163–4 | date = 1993 | pmid = 8477775 | doi = 10.1159/000474586 }}</ref> Nafarelin is marketed for medical use in both its free base (nafarelin) and acetate salt (nafarelin acetate) forms.<ref name="IndexNominum2000" />

==History== Nafarelin was introduced for medical use in 1990.<ref name="Drugs@FDA">{{Cite web|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019886|title=Drugs@FDA: FDA-Approved Drugs|access-date=2024-07-10|archive-date=2021-03-23|archive-url=https://web.archive.org/web/20210323051150/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019886|url-status=dead}}</ref><ref name="pmid2140979" /><ref name="pmid1984190">{{cite journal | vauthors = Conn PM, Crowley WF | title = Gonadotropin-releasing hormone and its analogues | journal = The New England Journal of Medicine | volume = 324 | issue = 2 | pages = 93–103 | date = January 1991 | pmid = 1984190 | doi = 10.1056/NEJM199101103240205 }}</ref>

==Society and culture==

===Generic names=== ''Nafarelin'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|BAN|British Approved Name}}, while ''nafaréline'' is its {{abbrlink|DCF|Dénomination Commune Française}} and ''nafarelin acetate'' is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014">{{cite book|vauthors=Elks J|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA846|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=846–|access-date=10 July 2024|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020305/https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA846|url-status=live}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA712|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=712–|access-date=2024-07-10|archive-date=2023-01-13|archive-url=https://web.archive.org/web/20230113020304/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA712|url-status=live}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA189|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=189–}}</ref><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/nafarelin.html|title=Nafarelin nasal Uses, Side Effects & Warnings|access-date=2024-07-10|archive-date=2018-08-28|archive-url=https://web.archive.org/web/20180828001729/https://www.drugs.com/international/nafarelin.html|url-status=live}}</ref> It is also known by its former developmental code name ''RS-94991'' or ''RS-94991-298''.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Drugs.com" />

===Brand names=== The major brand names of nafarelin are Synarel and Synarela.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> It has also been marketed under a number of other brand names including Synrelin, Synrelina, Nafarelil 0.2%, and Nasanyl 0.2%.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

===Availability=== Nafarelin is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, other European countries, Australia, Israel, Argentina, Brazil, Mexico, and Japan.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

==References== {{Reflist}}

==Further reading== {{refbegin}} * {{cite journal | vauthors = Barbieri RL | title = Comparison of the pharmacology of nafarelin and danazol | journal = American Journal of Obstetrics and Gynecology | volume = 162 | issue = 2 | pages = 581–585 | date = February 1990 | pmid = 2137975 | doi = 10.1016/0002-9378(90)90436-B }} * {{cite journal | vauthors = Chrisp P, Goa KL | title = Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions | journal = Drugs | volume = 39 | issue = 4 | pages = 523–551 | date = April 1990 | pmid = 2140979 | doi = 10.2165/00003495-199039040-00005 }} * {{cite journal | vauthors = Burry KA | title = Nafarelin in the management of endometriosis: quality of life assessment | journal = American Journal of Obstetrics and Gynecology | volume = 166 | issue = 2 | pages = 735–739 | date = February 1992 | pmid = 1531576 | doi = 10.1016/0002-9378(92)91705-F }} * {{cite journal | vauthors = Minaguchi H, Wong JM, Snabes MC | title = Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature | journal = The Journal of Reproductive Medicine | volume = 45 | issue = 6 | pages = 481–489 | date = June 2000 | pmid = 10900582 }} {{refend}}

Category:Gonadotropin-releasing hormone agonists Category:Decapeptides Category:Drugs developed by Pfizer Category:Puberty blockers Category:Feminizing hormone therapy