Renamed user 51g7z61hz5af2azs6k6 (talk | contribs) →Anxiety and depression: There is no warning of this in any package insert I have been able to find, only a listing as "unconfirmed reports", "unestablished causality", or "unknown frequency", like 10's of other items. Deleted references to "warnings" |
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{{Short description|Antiandrogen medication}} |
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{{sprotected2}} |
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{{Use dmy dates|date=October 2022}} |
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{{Drugbox |
{{Drugbox |
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| Watchedfields = changed |
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| verifiedrevid = 458461973 |
| verifiedrevid = 458461973 |
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| IUPAC_name = ''N''-(1,1-dimethylethyl)-3-oxo-<br>(5α,17β)-4-azaandrost-1-ene-17-carboxamide |
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| image = Finasteride.svg |
| image = Finasteride.svg |
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| width = 200 |
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| image2 = Finasteride-3D-balls.png |
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| image2 = Finasteride-from-xtal-3D-bs-17.png |
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| width2 = 250 |
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<!--Clinical data--> |
<!-- Clinical data --> |
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| tradename = Propecia, |
| tradename = Proscar, Propecia, Finide, others |
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| Drugs.com = {{drugs.com|monograph|finasteride}} |
| Drugs.com = {{drugs.com|monograph|finasteride}} |
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| MedlinePlus = a698016 |
| MedlinePlus = a698016 |
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| DailyMedID = Finasteride |
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| pregnancy_category = X (will cause birth defects in a fetus) |
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| pregnancy_AU = X |
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| pregnancy_category = |
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| routes_of_administration = [[Oral administration|By mouth]] |
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| class = [[5α-Reductase inhibitor]] |
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| ATC_prefix = G04 |
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| ATC_suffix = CB01 |
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| ATC_supplemental = {{ATC|D11|AX10}} |
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| legal_AU = S4 |
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| legal_CA = Rx-only |
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| legal_UK = POM |
| legal_UK = POM |
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| legal_UK_comment = <ref>{{cite web | title=Propecia 1 mg Film-Coated Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=27 July 2020 | url=https://www.medicines.org.uk/emc/product/2194/smpc | access-date=29 September 2020 | archive-date=20 September 2020 | archive-url=https://web.archive.org/web/20200920055119/https://www.medicines.org.uk/emc/product/2194/smpc | url-status=live }}</ref><ref>{{cite web | title=Proscar 5mg film-coated Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=10 July 2020 | url=https://www.medicines.org.uk/emc/product/1008/smpc | access-date=29 September 2020 | archive-date=24 September 2020 | archive-url=https://web.archive.org/web/20200924060320/https://www.medicines.org.uk/emc/product/1008/smpc | url-status=live }}</ref> |
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| legal_US = Rx-only |
| legal_US = Rx-only |
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| legal_US_comment = <ref name="Proscar FDA label">{{cite web | title=Proscar- finasteride tablet, film coated | website=DailyMed | date=15 November 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c01f541-1c88-400c-41a9-7cbb9dee50c0 | access-date=16 September 2020 | archive-date=26 April 2021 | archive-url=https://web.archive.org/web/20210426231856/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c01f541-1c88-400c-41a9-7cbb9dee50c0 | url-status=live }}</ref><ref name="Propecia FDA label" /> |
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| routes_of_administration = Oral |
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<!--Pharmacokinetic data--> |
<!-- Pharmacokinetic data --> |
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| bioavailability = 65%<ref name="LemkeWilliams2008">{{cite book|vauthors=Lemke TL, Williams DA|title=Foye's Principles of Medicinal Chemistry|edition=6th|url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1286|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6879-5|pages=1286–|access-date=4 December 2017|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031700/https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1286|url-status=live}}</ref> |
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| bioavailability = 63% |
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| protein_bound = 90%<ref name="LemkeWilliams2008" /> |
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| metabolism = [[Liver|Hepatic]] |
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| metabolism = [[Liver]] ([[CYP3A4]], [[aldehyde dehydrogenase|ALDH]])<ref name="LemkeWilliams2008" /> |
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| elimination_half-life = Elderly: 8 hours<br />Adults: 6 hours |
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| elimination_half-life = Adults: 5–6 hours<ref name="LemkeWilliams2008" /><br />Elderly: >8 hours<ref name="LemkeWilliams2008" /> |
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| excretion = Feces (57%) and urine (39%) as metabolites |
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| excretion = [[Feces]]: 57%<ref name="LemkeWilliams2008" /><br />[[Urine]]: 40%<ref name="LemkeWilliams2008" /> |
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<!--Identifiers--> |
<!-- Identifiers --> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 98319-26-7 |
| CAS_number = 98319-26-7 |
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| ATC_prefix = G04 |
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| ATC_suffix = CB01 |
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| ATC_supplemental = {{ATC|D11|AX10}} |
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| PubChem = 57363 |
| PubChem = 57363 |
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| IUPHAR_ligand = 6818 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB01216 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 51714 |
| ChemSpiderID = 51714 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 710 |
| ChEMBL = 710 |
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| synonyms = MK-906; YM-152; L-652,931; 17β-(''N''-tert-Butylcarbamoyl)-4-aza-5α-androst-1-en-3-one; ''N''-(1,1-Dimethylethyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide |
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<!--Chemical data--> |
<!-- Chemical data --> |
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| IUPAC_name = (1S,3aS,3bS,5aR,9aR,9bS,11aS)-''N''-tert-butyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide |
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| C=23 | H=36 | N=2 | O=2 |
| C=23 | H=36 | N=2 | O=2 |
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| SMILES = O=C(NC(C)(C)C)[C@@H]2[C@]1(CC[C@H]3[C@H]([C@@H]1CC2)CC[C@H]4NC(=O)\C=C/[C@]34C)C |
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| molecular_weight = 372.549 g/mol |
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| smiles = O=C(NC(C)(C)C)[C@@H]2[C@]1(CC[C@H]3[C@H]([C@@H]1CC2)CC[C@H]4NC(=O)\C=C/[C@]34C)C |
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| InChI = 1/C23H36N2O2/c1-21(2,3)25-20(27)17-8-7-15-14-6-9-18-23(5,13-11-19(26)24-18)16(14)10-12-22(15,17)4/h11,13-18H,6-10,12H2,1-5H3,(H,24,26)(H,25,27)/t14-,15-,16-,17+,18+,22-,23+/m0/s1 |
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| InChIKey = DBEPLOCGEIEOCV-WSBQPABSBG |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C23H36N2O2/c1-21(2,3)25-20(27)17-8-7-15-14-6-9-18-23(5,13-11-19(26)24-18)16(14)10-12-22(15,17)4/h11,13-18H,6-10,12H2,1-5H3,(H,24,26)(H,25,27)/t14-,15-,16-,17+,18+,22-,23+/m0/s1 |
| StdInChI = 1S/C23H36N2O2/c1-21(2,3)25-20(27)17-8-7-15-14-6-9-18-23(5,13-11-19(26)24-18)16(14)10-12-22(15,17)4/h11,13-18H,6-10,12H2,1-5H3,(H,24,26)(H,25,27)/t14-,15-,16-,17+,18+,22-,23+/m0/s1 |
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| StdInChIKey = DBEPLOCGEIEOCV-WSBQPABSSA-N |
| StdInChIKey = DBEPLOCGEIEOCV-WSBQPABSSA-N |
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}} |
}} |
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'''Finasteride''' ('''MK-906''', '''Proscar''' and '''Propecia''' by [[Merck & Co|Merck]], among other [[generic drug|generic names]]) is a synthetic drug for the treatment of [[benign prostatic hyperplasia]] (BPH) and [[male pattern baldness]] (MPB). It is a [[SRD5A2|type II]] [[5α-reductase inhibitor]]. 5α-reductase is an [[enzyme]] that converts [[testosterone]] to [[dihydrotestosterone]] (DHT). |
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<!-- Definition and medical uses --> |
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'''Finasteride''', sold under the brand names '''Proscar''' and '''Propecia''' among others, is a medication used to treat [[pattern hair loss]] and [[benign prostatic hyperplasia]] (BPH) in men.<ref name=AHFS2019>{{cite web |title=Finasteride Monograph for Professionals |url=https://www.drugs.com/monograph/finasteride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=5 March 2019 |archive-date=25 August 2018 |archive-url=https://web.archive.org/web/20180825002456/https://www.drugs.com/monograph/finasteride.html |url-status=live }}</ref> It can also be used to treat [[hirsutism|excessive hair growth]] in women.<ref name="Blume-PeytaviWhiting2008">{{cite book|url=https://books.google.com/books?id=pHrX2-huQCoC&pg=PA369|title=Hair Growth and Disorders|vauthors=Blume-Peytavi U, Whiting DA, Trüeb RM|date=26 June 2008|publisher=Springer Science & Business Media|isbn=978-3-540-46911-7|pages=369|access-date=10 December 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031700/https://books.google.com/books?id=pHrX2-huQCoC&pg=PA369|url-status=live}}</ref><ref name="TranssexualMgmnt2012">{{cite journal | vauthors = Knezevich EL, Viereck LK, Drincic AT | title = Medical management of adult transsexual persons | journal = Pharmacotherapy | volume = 32 | issue = 1 | pages = 54–66 | date = January 2012 | pmid = 22392828 | doi = 10.1002/PHAR.1006 | s2cid = 12853220 }}</ref> It is usually taken [[oral administration|orally]] but there are [[Topical medication|topical formulations]] for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles.<ref name=":0">{{cite journal | vauthors = Piraccini BM, Blume-Peytavi U, Scarci F, Jansat JM, Falqués M, Otero R, Tamarit ML, Galván J, Tebbs V, Massana E | display-authors = 6 | title = Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial | journal = Journal of the European Academy of Dermatology and Venereology | volume = 36 | issue = 2 | pages = 286–294 | date = February 2022 | pmid = 34634163 | pmc = 9297965 | doi = 10.1111/jdv.17738 }}</ref> |
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Finasteride is a [[5α-reductase inhibitor]] and therefore an [[antiandrogen]].<ref>{{cite book|vauthors=Ferri FF|title=Ferri's Clinical Advisor 2015 E-Book: 5 Books in 1|date=2014|publisher=Elsevier Health Sciences|isbn=9780323084307|page=580|url=https://books.google.com/books?id=icTsAwAAQBAJ&pg=PA580|access-date=7 May 2020|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031742/https://books.google.com/books?id=icTsAwAAQBAJ&pg=PA580|url-status=live}}</ref> It works by [[enzyme inhibitor|decreasing]] the [[biosynthesis|production]] of [[dihydrotestosterone]] (DHT) by about 70%.<ref name=AHFS2019/> |
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In addition to DHT, finasteride also inhibits the production of several anticonvulsant neurosteroids including [[allopregnanolone]], [[androstanediol]], and [[THDOC]].<ref>{{cite journal | vauthors = Samba Reddy D, Ramanathan G | title = Finasteride inhibits the disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesis | journal = Epilepsy & Behavior | volume = 25 | issue = 1 | pages = 92–7 | date = September 2012 | pmid = 22835430 | pmc = 3444667 | doi = 10.1016/j.yebeh.2012.05.024 }}</ref> |
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<!--Adverse effects and mechanism --> |
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[[Adverse effects]] from finasteride are rare;<ref name=Cochrane2010>{{cite journal | vauthors = Tacklind J, Fink HA, Macdonald R, Rutks I, Wilt TJ | title = Finasteride for benign prostatic hyperplasia | journal = The Cochrane Database of Systematic Reviews | issue = 10 | pages = CD006015 | date = October 2010 | volume = 2015 | pmid = 20927745 | doi = 10.1002/14651858.CD006015.pub3 | pmc = 8908761 }}</ref> however, some men experience [[sexual dysfunction]], [[depression (mood)|depression]], and [[gynecomastia|breast enlargement]].<ref name="Zak2019">{{cite journal | vauthors = Zakhem GA, Goldberg JE, Motosko CC, Cohen BE, Ho RS | title = Sexual dysfunction in men taking systemic dermatologic medication: A systematic review | journal = Journal of the American Academy of Dermatology | volume = 81 | issue = 1 | pages = 163–172 | date = July 2019 | pmid = 30905792 | doi = 10.1016/j.jaad.2019.03.043 | s2cid = 85497115 }}</ref><ref name=2014AArev>{{cite journal | vauthors = Varothai S, Bergfeld WF | title = Androgenetic alopecia: an evidence-based treatment update | journal = American Journal of Clinical Dermatology | volume = 15 | issue = 3 | pages = 217–30 | date = July 2014 | pmid = 24848508 | doi = 10.1007/s40257-014-0077-5 | s2cid = 31245042 }}</ref> In some men, sexual dysfunction may persist after stopping the medication.<ref name=Zax2019>{{cite journal | vauthors = Zakhem GA, Goldberg JE, Motosko CC, Cohen BE, Ho RS | title = Sexual dysfunction in men taking systemic dermatologic medication: A systematic review | journal = Journal of the American Academy of Dermatology | volume = 81 | issue = 1 | pages = 163–172 | date = July 2019 | pmid = 30905792 | doi = 10.1016/j.jaad.2019.03.043 | s2cid = 85497115 | quote = In studies addressing reversibility, most of these patients have resolution of sexual adverse effects after discontinuation of finasteride, and many have improvement of adverse effects over time with continued finasteride use. However, some studies describe a subset of patients with persistent adverse effects after discontinuation... Level 1 evidence evaluating sexual dysfunction as a primary outcome was available for finasteride. }}</ref><ref name=Tra2020>{{cite journal | vauthors = Traish AM | title = Post-finasteride syndrome: a surmountable challenge for clinicians | journal = Fertility and Sterility | volume = 113 | issue = 1 | pages = 21–50 | date = January 2020 | pmid = 32033719 | doi = 10.1016/j.fertnstert.2019.11.030 | s2cid = 211064052 | doi-access = free }}</ref> It may also hide the early symptoms of certain forms of [[prostate cancer]].<ref name=2014AArev/> |
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<!-- History, society, and culture --> |
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Finasteride was patented in 1984 and approved for medical use in 1992.<ref name=Fis2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=483 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA483 |access-date=7 May 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110031701/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA483 |url-status=live }}</ref> It is available as a [[generic medication]].<ref name="SataloffSclafani2015">{{cite book | vauthors = Sataloff RT, Sclafani AP | title = Sataloff's Comprehensive Textbook of Otolaryngology: Head & Neck Surgery: Facial Plastic and Reconstructive Surgery | url = https://books.google.com/books?id=acswCwAAQBAJ&pg=PA400 | date = 30 November 2015 | publisher = JP Medical Ltd | isbn = 978-93-5152-459-5 | pages = 400– | access-date = 4 December 2017 | archive-date = 10 January 2023 | archive-url = https://web.archive.org/web/20230110031702/https://books.google.com/books?id=acswCwAAQBAJ&pg=PA400 | url-status = live }}</ref> In 2021, it was the 88th most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Finasteride - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Finasteride | access-date = 14 January 2024 | archive-date = 6 February 2020 | archive-url = https://web.archive.org/web/20200206153249/https://clincalc.com/DrugStats/Drugs/Finasteride | url-status = live }}</ref> |
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{{TOC limit}} |
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==Medical uses== |
==Medical uses== |
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Finasteride has been used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate<ref name="Proscar FDA label" /> and for the treatment of male pattern hair loss (androgenetic alopecia) in men.<ref name="Propecia FDA label" /> |
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===Enlarged prostate=== |
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===Benign prostatic hyperplasia=== |
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Physicians |
Physicians sometimes prescribe finasteride for the treatment of benign prostatic hyperplasia (BPH), informally known as an enlarged [[prostate]].<ref>{{cite journal | vauthors = Smith AB, Carson CC | title = Finasteride in the treatment of patients with benign prostatic hyperplasia: a review | journal = Therapeutics and Clinical Risk Management | volume = 5 | issue = 3 | pages = 535–45 | date = June 2009 | pmid = 19707263 | pmc = 2710385 | doi = 10.2147/tcrm.s6195 | doi-access = free }}</ref> Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up during the night to urinate, hesitation at the start and end of urination, and decreased urinary flow.<ref>{{Cite web|date=20 October 2017|title=Benign prostate enlargement|url=https://www.nhs.uk/conditions/prostate-enlargement/|access-date=20 October 2020|website=nhs.uk|language=en|archive-date=18 October 2020|archive-url=https://web.archive.org/web/20201018014542/https://www.nhs.uk/conditions/prostate-enlargement/|url-status=live}}</ref> |
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The use of the drug showed significant sexual adverse effects such as erectile dysfunction and less sexual desire, in particular when obstructive symptoms due to an enlarged prostate were present.<ref name="pmid28453908">{{cite journal | vauthors = Corona G, Tirabassi G, Santi D, Maseroli E, Gacci M, Dicuio M, Sforza A, Mannucci E, Maggi M | display-authors = 6 | title = Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis | journal = Andrology | volume = 5 | issue = 4 | pages = 671–678 | date = July 2017 | pmid = 28453908 | pmc = | doi = 10.1111/andr.12353 | hdl = 11380/1132897 | s2cid = 3577324 | doi-access = free }} </ref> |
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===Male pattern baldness=== |
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As measured by hair counts, in a five-year study of men with mild to moderate [[Baldness|hair loss]], two out of three of the men who took 1 mg of finasteride daily regrew some hair. In contrast, all of the men in the study who were not taking finasteride lost hair. In the same study, based on photographs that were reviewed by an independent panel of dermatologists, 48% of those treated with finasteride experienced visible regrowth of hair, and a further 42% had no further loss. Average hair count in the treatment group remained above baseline, and showed an increasing difference from hair count in the placebo group, for all five years of the study. Finasteride is effective only for as long as it is taken; the hair gained or maintained is lost within 6–12 months of ceasing therapy.<ref>Rossi S (Ed.) (2004). ''[[Australian Medicines Handbook|Australian Medicines Handbook 2004]]''. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.{{page needed|date=September 2014}}</ref> In clinical studies, finasteride, like [[minoxidil]], was shown to work on both the crown area and the hairline,<ref name="pmid10365924">{{cite journal |author=Leyden J, Dunlap F, Miller B, ''et al.'' |title=Finasteride in the treatment of men with frontal male pattern hair loss |journal=Journal of the American Academy of Dermatology |volume=40 |issue=6 Pt 1 |pages=930–7 |date=June 1999 |pmid=10365924 |doi=10.1016/S0190-9622(99)70081-2}}</ref> but is most successful in the crown area. |
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===Scalp hair loss=== |
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A recent 10-year study of 118 men treated with 1 mg/day finasteride for androgenic alopecia found that 86% of men continued to benefit from treatment over the entire course of 10 years—showing increased or stable rates of hair growth—and only 14% experiencing any further hair loss. Interestingly, it was found that subjects who showed the most hair growth in their first year of treatment were more likely to have better hair growth after 5 years, with nearly 69% of these patients experiencing continued growth; however, many of those who experienced no growth in their first year of treatment were found to improve later on. It was also found that subjects who were older than 30 years of age tended to have better hair growth in the long run, presumably due to having experienced more hair loss by that point in their lives in comparison.{{citation needed|date=September 2014}} |
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Finasteride is also used to treat [[pattern hair loss|male pattern baldness]] (androgenic alopecia) in men, a condition that develops in up to 80% of Caucasian men aged 70 and over.<ref name="pmid29178529">{{cite journal | vauthors = Kanti V, Messenger A, Dobos G, Reygagne P, Finner A, Blumeyer A, Trakatelli M, Tosti A, Del Marmol V, Piraccini BM, Nast A, Blume-Peytavi U | title = Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men - short version | journal = Journal of the European Academy of Dermatology and Venereology | volume = 32 | issue = 1 | pages = 11–22 | date = January 2018 | pmid = 29178529 | doi = 10.1111/jdv.14624 | doi-access = free }}</ref><ref name="Propecia FDA label">{{cite web | title=Propecia- finasteride tablet, film coated | website=DailyMed | date=15 November 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e07adb4-7807-47d3-b9a9-2332a3047410 | access-date=16 September 2020 | archive-date=6 June 2021 | archive-url=https://web.archive.org/web/20210606214628/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e07adb4-7807-47d3-b9a9-2332a3047410 | url-status=live }}</ref> In the United States, finasteride and [[minoxidil]] are the only two FDA approved drugs for the treatment of male pattern hair loss as of 2017.<ref>{{cite journal | vauthors = Adil A, Godwin M | title = The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis | journal = Journal of the American Academy of Dermatology | volume = 77 | issue = 1 | pages = 136–141.e5 | date = July 2017 | pmid = 28396101 | doi = 10.1016/j.jaad.2017.02.054 | s2cid = 46036459 }}</ref> Treatment with finasteride slows further hair loss<ref name="Habif2015">{{cite book | vauthors = Habif TP | title = Clinical Dermatology | url = https://books.google.com/books?id=N_D5CQAAQBAJ&pg=PA934 | date = 23 April 2015 | publisher = Elsevier Health Sciences | isbn = 978-0-323-26607-9 | pages = 934– | access-date = 22 October 2016 | archive-date = 10 January 2023 | archive-url = https://web.archive.org/web/20230110031702/https://books.google.com/books?id=N_D5CQAAQBAJ&pg=PA934 | url-status = live }}</ref> and provides about 30% improvement in hair loss after six months of treatment, with effectiveness persisting as long as the drug is taken.<ref name="2014AArev"/> Taking finasteride leads to a reduction in scalp and serum DHT levels; by lowering scalp levels of DHT, finasteride can maintain or increase the amount of terminal hairs in the [[Hair follicle|anagen phase]] by inhibiting and sometimes reversing miniaturization of the hair follicle. Finasteride is most effective on the [[Crown (anatomy)|crown]] but can reduce hair loss in all areas of the scalp.<ref>{{cite journal | vauthors = Yim E, Nole KL, Tosti A | title = 5α-Reductase inhibitors in androgenetic alopecia | journal = Current Opinion in Endocrinology, Diabetes and Obesity | volume = 21 | issue = 6 | pages = 493–8 | date = December 2014 | pmid = 25268732 | doi = 10.1097/MED.0000000000000112 | s2cid = 30008068 }}</ref><ref>{{cite journal | vauthors = Gupta AK, Charrette A | title = The efficacy and safety of 5α-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefit-risk assessment of finasteride and dutasteride | journal = The Journal of Dermatological Treatment | volume = 25 | issue = 2 | pages = 156–61 | date = April 2014 | pmid = 23768246 | doi = 10.3109/09546634.2013.813011 | s2cid = 24833568 }}</ref> Finasteride has also been tested for pattern hair loss in women; however, the results were no better than placebo.<ref name="FPArev">{{cite journal | vauthors = Levy LL, Emer JJ | title = Female pattern alopecia: current perspectives | journal = International Journal of Women's Health | volume = 5 | pages = 541–56 | date = August 2013 | pmid = 24039457 | pmc = 3769411 | doi = 10.2147/IJWH.S49337 | doi-access = free }}</ref> Finasteride is less effective in the treatment of scalp hair loss than [[dutasteride]].<ref name="pmid32279398">{{cite journal | vauthors = Dhurat R, Sharma A, Rudnicka L, Kroumpouzos G, Kassir M, Galadari H, Wollina U, Lotti T, Golubovic M, Binic I, Grabbe S, Goldust M | title = 5-Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms, current concepts, comparative efficacy, and safety | journal = Dermatol Ther | volume = 33 | issue = 3 | pages = e13379 | date = May 2020 | pmid = 32279398 | doi = 10.1111/dth.13379 | s2cid = 215748750 | doi-access = free }}</ref><ref name="pmid30863034">{{cite journal | vauthors = Zhou Z, Song S, Gao Z, Wu J, Ma J, Cui Y | title = The efficacy and safety of dutasteride compared with finasteride in treating men with androgenetic alopecia: a systematic review and meta-analysis | journal = Clin Interv Aging | volume = 14 | pages = 399–406 | date = 2019 | pmid = 30863034 | pmc = 6388756 | doi = 10.2147/CIA.S192435 | doi-access = free }}</ref> |
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===Prostate cancer=== |
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Side effects were seen in only 5.9% of patients, and no patients reported [[depression (mood)|depression]] or [[gynecomastia]]. The authors concluded that the effectiveness of finasteride in treating androgenic alopecia does not reduce over time, even in older patients (including those over 40 years of age), and that it is well-tolerated.<ref name="pmid21910805">{{cite journal |author=Rossi A, Cantisani C, Scarnò M, Trucchia A, Fortuna MC, Calvieri S |title=Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up |journal=Dermatologic Therapy |volume=24 |issue=4 |pages=455–61 |year=2011 |pmid=21910805 |doi=10.1111/j.1529-8019.2011.01441.x}}</ref><ref name="pmid23159182">{{cite journal |author=Banka N, Bunagan MJ, Shapiro J |title=Pattern hair loss in men: diagnosis and medical treatment |journal=Dermatologic Clinics |volume=31 |issue=1 |pages=129–40 |date=January 2013 |pmid=23159182 |doi=10.1016/j.det.2012.08.003}}</ref> This study specifically looked at users who continued using the medication. A recent [[case control]] evaluated male pattern baldness patients with psychiatric sequellae after discontinuation of finasteride, and reported depressive symptomatology and [[suicide|suicidal ideation]] for those who also experienced sexual side effects during use of the drug.<ref name="Irwig MS 1220–3">{{cite journal |author=Irwig MS |title=Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects |journal=The Journal of Clinical Psychiatry |volume=73 |issue=9 |pages=1220–3 |date=September 2012 |pmid=22939118 |doi=10.4088/JCP.12m07887}}</ref> |
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In males aged 55 years old and over finasteride decreases the risk of low-grade [[prostate cancer]] but may increase the risk of high-grade prostate cancer and has no effect on overall survival.<ref>{{cite web |title=Finasteride for Prostate Cancer Prevention |url=https://www.cancer.gov/types/prostate/research/finasteride-reduces-low-grade |website=National Cancer Institute |access-date=8 February 2020 |date=28 August 2013 |archive-date=6 February 2020 |archive-url=https://web.archive.org/web/20200206153247/https://www.cancer.gov/types/prostate/research/finasteride-reduces-low-grade |url-status=live }}</ref> |
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A 2010 review found a 25% reduction in the risk of prostate cancer with 5α-reductase inhibitor.<ref name="pmid20977593">{{cite journal | vauthors = Wilt TJ, Macdonald R, Hagerty K, Schellhammer P, Tacklind J, Somerfield MR, Kramer BS | title = 5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review | journal = BJU Int. | volume = 106 | issue = 10 | pages = 1444–51 | year = 2010 | pmid = 20977593 | doi = 10.1111/j.1464-410X.2010.09714.x | s2cid = 22178061 | doi-access = free }}</ref> A follow-up study of the [[Medicare (United States)|Medicare]] claims of participants in a 10-year Prostate Cancer Prevention Trial suggests the reduction in prostate cancer is maintained even after discontinuation of treatment.<ref>{{cite journal | vauthors = Unger JM, Hershman DL, Till C, Tangen CM, Barlow WE, Ramsey SD, Goodman PJ, Thompson IM | title = Using Medicare Claims to Examine Long-term Prostate Cancer Risk of Finasteride in the Prostate Cancer Prevention Trial | journal = Journal of the National Cancer Institute | volume = 110 | issue = 11 | pages = 1208–1215 | date = March 2018 | pmid = 29534197 | pmc = 6235685 | doi = 10.1093/jnci/djy035 }}</ref> However, 5α-reductase inhibitors have been found to increase the risk of developing certain rare but aggressive forms of prostate cancer (27% risk increase), although not all studies have observed this.<ref name=Hirshburg2016>{{cite journal|vauthors=Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS|year=2016|title=Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review|journal=J Clin Aesthet Dermatol|volume=9|issue=7|pages=56–62|pmc=5023004|pmid=27672412}}</ref> No impact of 5-α-reductase inhibitor on survival has been found in people with prostate cancer.<ref name=Hirshburg2016 /> |
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===Excessive hair growth=== |
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Some users, in an effort to save money, buy Proscar (finasteride 5 mg) instead of Propecia, and split the Proscar pills into several parts to approximate the Propecia dosage.<ref>{{ cite news |url=http://www.nytimes.com/1999/03/19/business/new-profits-in-old-bottles-companies-find-bonus-in-drugs-that-cure-several-ills.html?pagewanted=all |title=New Profits in Old Bottles; Companies Find Bonus in Drugs That Cure Several Ills |last=Morrow |first=David J. |publisher= ''The New York Times'' |date=March 19, 1999 |accessdate= June 6, 2010 }}</ref> The pills are coated to prevent contact with the active ingredient during handling, and the dust or crumbs from broken Proscar tablets should be kept away from pregnant women or women who may become pregnant.<ref>{{cite web|url=http://www.merck.com/product/usa/pi_circulars/p/proscar/proscar_ppi.pdf|title=Patient Information About Proscar|publisher=Merck Sharp & Dohme Corp.}}</ref> |
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Finasteride has been found to be effective in the treatment of [[hirsutism]] (excessive facial and/or body hair growth) in women. In a study of 89 women with [[hyperandrogenism]] due to [[persistent adrenarche syndrome]], finasteride produced a 93% reduction in facial hirsutism and a 73% reduction bodily hirsutism after 2 years of treatment. Other studies using finasteride for hirsutism have also found it to be clearly effective.<ref name="Blume-PeytaviWhiting2008" /> |
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===Transgender hormone therapy=== |
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Finasteride is sometimes used in [[hormone replacement therapy (male-to-female)|hormone replacement therapy]] for [[transgender women]] due to its [[antiandrogen]]ic effects, in combination with a form of [[estrogen (medication)|estrogen]]. However, little [[clinical trial|clinical research]] of finasteride use for this purpose has been conducted and evidence of safety or efficacy is limited.<ref name="TranssexualMgmnt2012"/> Moreover, caution has been recommended when prescribing finasteride to transgender women, as finasteride may be associated with side effects such as depression, anxiety, and suicidal ideation, symptoms that are particularly prevalent in the transgender population and in others at high risk already.<ref name="Trüeb2017">{{cite journal | vauthors = Trüeb RM | title = Discriminating in favour of or against men with increased risk of finasteride-related side effects? | journal = Experimental Dermatology | volume = 26 | issue = 6 | pages = 527–528 | date = June 2017 | pmid = 27489125 | doi = 10.1111/exd.13155 | quote = [...] caution is recommended while prescribing oral finasteride to male-to-female transsexuals, as the drug has been associated with inducing depression, anxiety and suicidal ideation, symptoms that are particularly common in patients with gender dysphoria, who are already at a high risk.[9] | s2cid = 36236057 | doi-access = free }}</ref> |
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Finasteride is sometimes used in [[hormone replacement therapy]] for [[male-to-female transsexual]]s in combination with a form of [[estrogen]] due to its [[antiandrogen]] properties.<ref name="pmid16286768">{{cite journal |author=Gooren L |title=Hormone treatment of the adult transsexual patient |journal=Hormone Research |volume=64 |issue=Suppl 2 |pages=31–6 |year=2005 |pmid=16286768 |doi=10.1159/000087751}}</ref><ref name="pmid22392828">{{cite journal |author=Knezevich EL, Viereck LK, Drincic AT |title=Medical management of adult transsexual persons |journal=Pharmacotherapy |volume=32 |issue=1 |pages=54–66 |date=January 2012 |pmid=22392828 |doi=10.1002/PHAR.1006}}</ref> However, little [[clinical trial|clinical research]] of finasteride use for this purpose has been conducted and evidence of efficacy is limited. Indeed, finasteride is a substantially weaker antiandrogen in comparison to conventional antiandrogens like [[spironolactone]] and [[cyproterone acetate]]. Finasteride has also been found to mitigate the effects of withdrawal after chronic alcohol use.<ref>{{cite journal |author=Finn DA, Long SL, Tanchuck MA, Crabbe JC |title=Interaction of chronic ethanol exposure and finasteride: sex and strain differences |journal=Pharmacology, Biochemistry, and Behavior |volume=78 |issue=3 |pages=435–43 |date=July 2004 |pmid=15251252 |doi=10.1016/j.pbb.2004.04.016}}</ref> |
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==Adverse effects== |
==Adverse effects== |
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In a four year controlled clinical study, 3040 patients with symptomatic benign prostatic hyperplasia were treated with 5 mg per day finasteride or placebo. Discontinuation rates due to adverse reactions related to sexual function were 3.7% in the finasteride arm and 2.1% in the placebo arm. Sexual effects were the most common type of adverse reaction.<ref>{{cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020788s024lbl.pdf |title=www.accessdata.fda.gov |format= |work= |accessdate=}}{{full|date=September 2014}}</ref> |
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A 2010 Cochrane review of finasteride for BPH found that, in men with a weighted mean age of 62.4, adverse effects are "rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo."<ref name=Cochrane2010/> {{asof|2016}} fresh evidence suggested such effects, along with disturbed [[neurosteroid]] production, may persist after finasteride use is stopped.<ref>{{Cite book| vauthors = Patisaul HB, Belcher SM |url=https://oxford.universitypressscholarship.com/view/10.1093/acprof:oso/9780199935734.001.0001/acprof-9780199935734-chapter-5|title=Receptor and Enzyme Mechanisms as Targets for Endocrine Disruptors|date=18 May 2017 |publisher=Oxford University Press |volume=1 |doi=10.1093/acprof:oso/9780199935734.003.0005 |page=127|isbn=9780190678524}}</ref> |
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In 12 month duration double-blind clinical trials including more than 3000 patients, adverse effects included decreased libido (5% in the finasteride group and 3% in the placebo group), erectile dysfunction (8% finasteride, 3% placebo), and ejaculation disorder (2% finasteride, 0.6% placebo).<ref name="Edwards JE, Moore RA 2002 14">{{cite journal |author=Edwards JE, Moore RA |title=Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials |journal=BMC Urology |volume=2 |issue= |pages=14 |date=December 2002 |pmid=12477383 |pmc=140032 |doi=10.1186/1471-2490-2-14}}</ref> |
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Finasteride is contraindicated in pregnancy.<ref name="fdapropecia2014">{{cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020788s024lbl.pdf |title=PROPECIA Prescribing Information |publisher=US Food & Drug Administration / Merck & Co., Inc. |access-date=30 January 2020 |archive-date=10 February 2017 |archive-url=https://web.archive.org/web/20170210151045/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020788s024lbl.pdf |url-status=live }}</ref><ref name="fdaproscar2010">{{cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020180s037lbl.pdf |title=PROSCAR Prescribing Information |publisher=US Food & Drug Administration / Merck & Co., Inc. |access-date=30 January 2020 |archive-date=10 February 2017 |archive-url=https://web.archive.org/web/20170210114729/http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020180s037lbl.pdf |url-status=live }}</ref> The [[Food and Drug Administration]] advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride.<ref>{{cite web | url = https://www.fda.gov/media/70929/download | title = Deferral of Blood and Plasma donors – Medications | publisher = [[FDA]] | date = 28 July 1993 | access-date = 30 January 2020 | archive-date = 14 December 2019 | archive-url = https://web.archive.org/web/20191214104503/https://www.fda.gov/media/70929/download | url-status = live }}</ref> |
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===Prostate cancer=== |
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The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade [[prostate cancer]].<ref>[http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258529.htm 5α-reductase inhibitors (5-ARIs): Label Change – Increased Risk of Prostate Cancer | U.S. Department of Health & Human Services]{{full|date=September 2014}}</ref> While the effect of finasteride on the risk of developing prostate cancer has not been established, evidence suggests it may temporarily reduce the growth and prevalence of benign prostate tumors, but could also mask the early detection of prostate cancer. The primary concern is patients who develop prostate cancer while taking finasteride for benign prostatic hyperplasia, which in turn could delay diagnosis and early treatment of the prostate cancer, thereby potentially increasing the risk of these patients developing high-grade prostate cancer.<ref name="pmid20357287">{{cite journal |author=Walsh PC |title=Chemoprevention of prostate cancer |journal=The New England Journal of Medicine |volume=362 |issue=13 |pages=1237–8 |date=April 2010 |pmid=20357287 |doi=10.1056/NEJMe1001045}}</ref> |
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The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade [[prostate cancer]], as the treatment of BPH lowers PSA ([[prostate-specific antigen]]), which could mask the development of prostate cancer.<ref>FDA. Posted 9 June 2011. [https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258529.htm 5-alpha reductase inhibitors (5-ARIs): Label Change – Increased Risk of Prostate Cancer] {{Webarchive|url=https://web.archive.org/web/20170118091754/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258529.htm |date=18 January 2017 }}</ref><ref name="pmid20357287">{{cite journal | vauthors = Walsh PC | title = Chemoprevention of prostate cancer | journal = The New England Journal of Medicine | volume = 362 | issue = 13 | pages = 1237–8 | date = April 2010 | pmid = 20357287 | doi = 10.1056/NEJMe1001045 }}</ref> Although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not increased, there are post-marketing reports of breast cancer in association with its use, though available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers.<ref name="Propecia FDA label" /><ref>Medicines and Healthcare products Regulatory Agency Drug Safety Update. December 2009 [http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087725 Finasteride: potential risk of male breast cancer] {{Webarchive|url=https://web.archive.org/web/20141025225536/http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087725 |date=25 October 2014 }}</ref> A 2018 [[meta-analysis]] found no higher risk of breast cancer with 5α-reductase inhibitors.<ref name="pmid29697934">{{cite journal | vauthors = Wang J, Zhao S, Luo L, Li E, Li X, Zhao Z | title = 5-alpha Reductase Inhibitors and risk of male breast cancer: a systematic review and meta-analysis | journal = Int Braz J Urol | volume = 44 | issue = 5 | pages = 865–873 | date = 2018 | pmid = 29697934 | pmc = 6237523 | doi = 10.1590/S1677-5538.IBJU.2017.0531 }}</ref> Some men develop [[gynecomastia]] (breast development or enlargement) following finasteride usage.<ref name="Narula2014">{{cite journal|vauthors=Narula HS, Carlson HE|title=Gynaecomastia-pathophysiology, diagnosis and treatment|journal=Nat Rev Endocrinol|date=August 2014|pmid=25112235|doi=10.1038/nrendo.2014.139|volume=10|issue=11|pages=684–698|s2cid=40159424|url=https://touroscholar.touro.edu/tuncom_pubs/54|access-date=4 July 2019|archive-date=4 December 2020|archive-url=https://web.archive.org/web/20201204085804/https://touroscholar.touro.edu/tuncom_pubs/54/|url-status=live}}</ref><ref name="Drugs">{{Cite journal|vauthors=Deepinder F, Braunstein GD |title=Drug-induced gynecomastia: an evidence-based review.|journal=Expert Opinion on Drug Safety |volume=11 |issue=5 |pages=779–795 |year=2012 |pmid=22862307 |doi=10.1517/14740338.2012.712109|s2cid=22938364}}</ref><ref>{{cite journal | vauthors = Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF | title = Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | pages = CD007004 | date = October 2020 | issue = 10 | pmid = 33107592 | doi = 10.1002/14651858.CD007004.pub4 | pmc = 8094274 }}</ref><ref>{{cite journal | vauthors = Aiman U, Haseeen MA, Rahman SZ | title = Gynecomastia: An ADR due to drug interaction | journal = Indian Journal of Pharmacology | volume = 41 | issue = 6 | pages = 286–7 | date = December 2009 | pmid = 20407562 | pmc = 2846505 | doi = 10.4103/0253-7613.59929 | doi-access = free }}</ref> The risk of gynecomastia with 5α-reductase inhibitors is low at about 1.5%.<ref name="pmid27784557" /> Depressive symptoms and suicidality have been reported.<ref name="pmid28456011">{{cite journal | vauthors = Locci A, Pinna G | title = Neurosteroid biosynthesis downregulation and changes in GABAA receptor subunit composition: A biomarker axis in stress-induced cognitive and emotional impairment | journal = Br. J. Pharmacol. | volume = 174| issue = 19| pages = 3226–3241| year = 2017 | pmid = 28456011 | doi = 10.1111/bph.13843 | pmc=5595768}}</ref> |
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The 2005 [[Prostate Cancer Prevention Trial]] (PCPT) showed at a dosage of 5 mg per day, as is commonly prescribed for BPH, participants taking finasteride were 25% less likely to have developed prostate cancer at the end of the trial compared to those taking a placebo.<ref name = PCPT>{{cite web |url=http://www.cancer.org/cancer/prostatecancer/overviewguide/prostate-cancer-overview-prevention |title=Can Prostate Cancer Be Prevented? |publisher=American Cancer Society |date=August 27, 2013 |accessdate=September 3, 2013}}</ref> It appeared (incorrectly) that finasteride increased the specificity and selectivity of prostate cancer detection, thus creating an apparently increased rate of high [[Gleason Grading System|Gleason grade tumor]]. A 2008 update of this study found that finasteride reduces the incidence of prostate cancer by 30%. In the original study, the smaller prostate caused by finasteride facilitated detection of cancer nests and aggressive-looking cells. Most of the men in the study who had both low and high-grade prostate cancer chose to be treated, and many had their prostates removed. A pathologist then carefully examined each of those 500 prostates and compared the kinds of cancers found at surgery to those initially diagnosed at biopsy. This study concluded that finasteride did not increase the risk of high-grade prostate cancer.<ref>{{cite news |author=Gina Kolata |title=New Take on a Prostate Drug, and a New Debate |url=http://www.nytimes.com/2008/06/15/health/15prostate.html |newspaper=[[NY Times]] |date=June 15, 2008 |accessdate=2008-06-15 }}</ref><ref name="pmid19138953">{{cite journal |author=Redman MW, Tangen CM, Goodman PJ, Lucia MS, Coltman CA, Thompson IM |title=Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach |journal=Cancer Prevention Research |volume=1 |issue=3 |pages=174–81 |date=August 2008 |pmid=19138953 |pmc=2844801 |doi=10.1158/1940-6207.CAPR-08-0092}}</ref> |
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===Sexual |
===Sexual adverse effects=== |
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Use of finasteride is associated with an increased risk of [[sexual dysfunction]] including [[erectile dysfunction]], [[Hypoactive sexual desire disorder|decreased libido]] and ejaculatory dysfunction.<ref name="Lee2019">{{cite journal |vauthors = Lee S, Lee YB, Choe SJ, Lee WS |title = Adverse Sexual Effects of Treatment with Finasteride or Dutasteride for Male Androgenetic Alopecia: A Systematic Review and Meta-analysis |journal=Acta Derm Venereol |volume=99 |issue=1 |pages=12–17 |year=2019 |pmid=30206635 |doi=10.2340/00015555-3035|doi-access=free }}</ref><ref name="Zak2019" /> Sexual adverse effects of finasteride and dutasteride have been linked to lower [[quality of life]] and ability to maintain an intimate relationship, and can cause stress in relationships.<ref name="Gur2013">{{cite journal | vauthors=Gur S, Kadowitz PJ, Hellstrom WJ | title=Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation |journal=Expert Opinion on Drug Safety |volume=12 |issue=1 |pages=81–90 |date=January 2013 |pmid=23173718 |doi=10.1517/14740338.2013.742885 |s2cid=11624116}}</ref> |
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There are [[case reports]] of persistent diminished libido or erectile dysfunction, even after stopping the drug.<ref name="pmid21176115">{{cite journal |author=Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML |title=Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients |journal=The Journal of Sexual Medicine |volume=8 |issue=3 |pages=872–84 |date=March 2011 |pmid=21176115 |doi=10.1111/j.1743-6109.2010.02157.x}}</ref><ref>[http://www.lakemedelsverket.se/SPC_PIL/Pdf/humpil/Propecia%201%20mg%20tablet.pdf Package Leaflet Information for the User], Swedish package insert for Propecia 1mg.</ref><ref name="leaflet">[http://www.merck.com/product/usa/pi_circulars/p/propecia/propecia_ppi.pdf PROPECIA® (finasteride) | Merck & Co., Inc.]</ref><ref><http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm299754.htm?utm_source=fdaSearch&utm_medium=website&utm_term=finasteride&utm_content=2>{{full|date=September 2014}}</ref><ref><http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/020180s039ltr.pdf>{{full|date=September 2014}}</ref><ref>{{cite news |url=http://www.businessweek.com/ap/2012-04/D9U3HR3G0.htm |agency=Associated Press |date=April 12, 2012 |title=FDA adds new side effects to finasteride label |work=Bloomberg Business Week |accessdate=September 3, 2014}}</ref> |
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The adverse effect profiles of finasteride are somewhat different for its indications of hair loss and BPH. |
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===Anxiety and depression=== |
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Mood disorders were not observed as an important adverse effect in the phase 3 trials leading to regulatory approval of finasteride for the treatment of benign prostatic hyperplasia.<ref name="Edwards JE, Moore RA 2002 14"/> Nonetheless, a variety of small studies have suggested a possible connection.<ref name="pmid16834758">{{cite journal |author=Finn DA, Beadles-Bohling AS, Beckley EH, ''et al.'' |title=A new look at the 5alpha-reductase inhibitor finasteride |journal=CNS Drug Reviews |volume=12 |issue=1 |pages=53–76 |year=2006 |pmid=16834758 |doi=10.1111/j.1527-3458.2006.00053.x}}</ref> |
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====Finasteride for androgenetic alopecia (hair loss in men)==== |
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In a small study examining the use of finasteride to treat [[hirsutism]] in women, fewer patients in the finasteride-treated group reported depression relative to the control group.<ref>{{cite journal |author=Ciotta L, Cianci A, Calogero AE, ''et al.'' |title=Clinical and endocrine effects of finasteride, a 5 alpha-reductase inhibitor, in women with idiopathic hirsutism |journal=Fertility and Sterility |volume=64 |issue=2 |pages=299–306 |date=August 1995 |pmid=7615107}}</ref> |
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The most common adverse effects of finasteride taken for hair loss are: decrease in sex drive, erectile dysfunction and decrease in amount of semen.<ref name="fdapropecia2014" />{{rp|17}} |
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In addition, finasteride has been reported in [[case reports]] to cause sexual problems which persist after stopping the medication.<ref name=Tra2020/><ref name=Zax2019/> A 2012 update to the FDA label noted reports of decreased sex drive, problems with ejaculation and difficulty achieving an erection which continued after stopping the medication. The update also referenced reports of testicular pain and "male infertility and/or poor quality of semen."<ref name="fdapropecia2014" />{{rp|17}}<ref name="2014AArev" /><ref>{{cite web |author=FDA |date=11 April 2012 |url=https://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm299754.htm |title=Questions and Answers: Finasteride Label Changes |publisher=US FDA |access-date=26 October 2014 |archive-date=18 August 2014 |archive-url=https://web.archive.org/web/20140818144525/http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm299754.htm |url-status=live }}</ref><ref name="pmid27784557">{{cite journal |vauthors = Trost L, Saitz TR, Hellstrom WJ |title = Side Effects of 5-Alpha Reductase Inhibitors: A Comprehensive Review |journal=Sex Med Rev |volume=1 |issue=1 |pages=24–41 |year=2013 |pmid=27784557 |doi=10.1002/smrj.3 }}</ref> |
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Another study with a larger sample size of 128 men, though no women, also at a dose of 1 mg per day, found that finasteride increased both [[Beck Depression Inventory|BDI]] and [[Hospital Anxiety and Depression Scale|HADS]] depression scores significantly.<ref name="pmid17026771">{{cite journal |author=Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A |title=Finasteride induced depression: a prospective study |journal=BMC Clinical Pharmacology |volume=6 |issue= |pages=7 |year=2006 |pmid=17026771 |pmc=1622749 |doi=10.1186/1472-6904-6-7}}</ref> The authors concluded that finasteride should be prescribed cautiously to patients at a high risk of depression. |
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====Finasteride for BPH==== |
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A study comparing depression in impotent men with a history of exposure to finasteride found that they experienced greater depression and suicidal ideation relative to non-impotent men without a history of finasteride exposure. The authors did not comment on the relative extent to which sexual dysfunction and prior finasteride treatment might have contributed to the depression.<ref name="Irwig MS 1220–3"/> |
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The most common adverse sexual effects of finasteride for BPH are: trouble getting or keeping an erection, decrease in sex drive, decreased volume of ejaculate and ejaculation disorders.<ref name="fdaproscar2010" />{{rp|16}} |
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A 2010 Cochrane review found that men taking finasteride for BPH (with a mean age of 62.4) are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder for the first year of treatment. The rates became indistinguishable from placebo after 2–4 years and these side effects usually got better over time.<ref name="Cochrane2010" /> |
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===Male breast cancer=== |
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In December 2009, the [[Medicines and Healthcare products Regulatory Agency]] in the UK announced new drug safety advice on finasteride and the potential risk of male breast cancer. The agency concluded that, although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not significantly increased, a higher risk of male breast cancer with finasteride use cannot be excluded. A warning on this risk will be included in the product information.<ref>{{cite web|url=http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Patient-Safety/MHRA-drug-safety-advice-Finasteride-and-potential-risk-of-male-breast-cancer/|title=MHRA drug safety advice: Finasteride and potential risk of male breast cancer |date=4 December 2009|accessdate=4 December 2009}}</ref> Merck revised the United States' warning in consumer and medical leaflets to include the risk of male breast cancer.<ref name="leaflet" /> |
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=== |
===Long-term=== |
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Finasteride may cause persistent adverse sexual, neurological and physical effects in a subset of men.<ref name=Zax2019/> A 2019 metastudy surveyed the literature on the reversibility of finasteride's side effects. It identified three studies which demonstrated full reversibility of side effects and eleven that describe patients with irreversible adverse events. The findings were most convincing in a retrospective review of about 12,000 patients that 1.4% of the cohort developed persistent ED<ref name="Zax2019" /> (ED lasting longer than 90 days post-withdrawal).<ref>{{cite journal | vauthors = Kiguradze T, Temps WH, Yarnold PR, Cashy J, Brannigan RE, Nardone B, Micali G, West DP, Belknap SM | display-authors = 6 | title = Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride | journal = PeerJ | volume = 5 | pages = e3020 | date = 9 March 2017 | pmid = 28289563 | pmc = 5346286 | doi = 10.7717/peerj.3020 | doi-access = free }}</ref> |
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Finasteride is in the FDA [[pregnancy category]] X. This means that it is known to cause [[birth defects]] in a [[fetus]]. Women who are or who may become pregnant must not handle crushed or broken finasteride tablets, because the medication could be absorbed through the skin. Finasteride is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed. It is not known whether finasteride passes into [[breast milk]], and thus should not be taken by breastfeeding women. Finasteride may pass into the [[semen]] of men, but Merck states that a pregnant woman's contact with the semen of a man taking finasteride is not an issue for concern. Finasteride is known to affect blood donations, and potential donors are typically restricted for at least a month after their most recent dose.<ref>{{cite web|url=http://www.fda.gov/Cber/bldmem/072893.pdf|title=FDA guidance on blood donors and medications|publisher=[[U.S. Food and Drug Administration]]|accessdate=01-02-2009|format=pdf |archiveurl = http://web.archive.org/web/20051031172818/http://www.fda.gov/Cber/bldmem/072893.pdf |archivedate = October 31, 2005}}</ref> |
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== Post-finasteride syndrome == |
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===Interference with doping assays=== |
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Reports of long-term, post-discontinuation adverse effects in some fraction of former finasteride users have led to a proposed post-finasteride syndrome, although some within the medical community question whether there is enough evidence to support a causal relationship between finasteride usage and PFS.<ref>{{cite journal | vauthors = Traish AM | title = Post-finasteride syndrome: a surmountable challenge for clinicians | journal = Fertility and Sterility | volume = 113 | issue = 1 | pages = 21–50 | date = January 2020 | pmid = 32033719 | doi = 10.1016/j.fertnstert.2019.11.030 | s2cid = 211064052 | doi-access = free }}</ref> |
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Many sports organizations have banned finasteride because it can be used to mask [[anabolic steroids|steroid]] abuse.<ref>{{cite news| url=http://query.nytimes.com/gst/fullpage.html?sec=health&res=9F02E2DB153FF93AA25752C0A9609C8B63&n=Top%2fReference%2fTimes%20Topics%2fSubjects%2fO%2fOlympic%20Games | work=The New York Times | title=Skin Deep; Fighting Baldness, and Now an Olympic Ban | first=Richard | last=Sandomir | date=2006-01-19 | accessdate=2010-05-02}}</ref> Since 2005, finasteride has been on the [[World Anti-Doping Agency]]'s list of banned substances. However, it was removed from the list in 2009.<ref>[http://www.wada-ama.org/rtecontent/document/QA_Finasteride.pdf World Anti-Doping Agency Q&A: Status of Finasteride]{{dead link|date=September 2014}}</ref> Notable athletes who used finasteride for hair loss and were banned from international competition include [[Skeleton (sport)|skeleton racer]] [[Zach Lund]], [[Bobsleigh|bobsledder]] [[Sebastien Gattuso]], [[Football (soccer)|footballer]] [[Romário]] and [[Goaltender|ice hockey goaltender]] [[José Théodore]].<ref>{{cite news | url = http://tsn.ca/nhl/story/?id=154231 | title = Theodore's hair tonic causes positive test | publisher = TSN | date = 2006-02-10 | accessdate = 2006-07-22}}{{dead link|date=September 2014}}</ref> |
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Individuals claiming to experience PFS report sexual, neurological, hormonal and psychological side effects that persist for an extended period after stopping the drug.<ref name="Margo">{{cite web | vauthors = Margo J | work = Australian Financial Review | date = 26 September 2012 | url = http://www.afr.com/p/lifestyle/mens_health/looking_at_care_with_critical_eye_ZRbAzUV4cRxZhspW7YRwBJ | title = Looking at care with a critical eye |archive-url=https://web.archive.org/web/20121114220945/http://www.afr.com/p/lifestyle/mens_health/looking_at_care_with_critical_eye_ZRbAzUV4cRxZhspW7YRwBJ |archive-date=14 November 2012 }}</ref> Reported symptoms include penile [[atrophy]] and tissue changes, [[decreased ejaculate volume]] and quality, reduced libido, erectile dysfunction, loss of penile sensitivity, decreased orgasm sensation, dry skin, metabolic changes, muscle and strength loss, [[gynecomastia]], depression, anxiety, panic attacks, insomnia, [[anhedonia]], concentration problems, memory impairment and [[suicidal ideation]].<ref name="Maksym-2019" /> A meta-analysis found significant association between finasteride use and post-discontinuation depression, suicidal ideation, and sexual dysfunction, but the quality of evidence was limited.<ref name="Pompili2021Depression">{{cite journal |vauthors=Pompili M, Magistri C, Maddalena S, Mellini C, Persechino S, Baldessarini RJ |date=1 May 2021 |title=Risk of Depression Associated With Finasteride Treatment |journal=Journal of Clinical Psychopharmacology |volume=41 |issue=3 |pages=304–309 |doi=10.1097/JCP.0000000000001379 |pmid=33814544 |s2cid=233028103}}</ref> |
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==Mechanism of action== |
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Testosterone in males is produced primarily in the [[testicles]], but also in the [[adrenal gland]]s. The majority of testosterone in the body is bound to [[sex hormone-binding globulin]] (SHBG), a protein produced in the liver that transports testosterone through the bloodstream, prevents its metabolism, and prolongs its half-life. Once it becomes unbound from SHBG, free testosterone can enter cells throughout the body. In certain tissues, notably the scalp, skin, and prostate, testosterone is converted into [[5α-dihydrotestosterone]] (DHT) by the enzyme [[5α-reductase]]. DHT is a more powerful androgen than testosterone (as it has approximately 3-10 times the potency at the [[androgen receptor]], the site of action of the androgen hormones), so 5α-reductase can be thought to amplify the androgenic effect of testosterone in the tissues in which it's found.{{citation needed|date=September 2014}} |
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The status of PFS as a legitimate and distinct medical pathology remains a subject of debate. A 2019 editorial in ''[[The BMJ]]'' called post-finasteride syndrome "ill defined and controversial".<ref>{{cite journal | vauthors = Gray SL, Semla TP | title = Post-finasteride syndrome | journal = BMJ | volume = 366 | issue = | pages = l5047 | date = August 2019 | pmid = 31399423 | doi = 10.1136/bmj.l5047 | s2cid = 199518161 }}</ref> Some have argued that it has common features with other self-diagnosed "mystery syndromes" such as [[Morgellons]] or [[multiple chemical sensitivity]], while others, including some in the biomedical research community, have concluded based on the available evidence that it represents a real and serious condition.<ref name="Tra2020" /> There is no known underlying biological mechanism for the proposed syndrome, and its incidence is unclear.<ref>{{cite journal | vauthors = Gray SL, Semla TP | title = Post-finasteride syndrome | journal = BMJ | volume = 366 | pages = l5047 | date = August 2019 | pmid = 31399423 | doi = 10.1136/bmj.l5047 | s2cid = 199518161 }}</ref> A lack of clear diagnostic criteria and the variable reporting fraction in different health-care settings make the problem challenging to evaluate.<ref name="Maksym-2019">{{cite journal | vauthors = Maksym RB, Kajdy A, Rabijewski M | title = Post-finasteride syndrome - does it really exist? | journal = The Aging Male | volume = 22 | issue = 4 | pages = 250–259 | date = December 2019 | pmid = 30651009 | doi = 10.1080/13685538.2018.1548589 | s2cid = 58569946 | doi-access = free }}</ref> |
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Finasteride, a 4-azasteroid and [[structural analogue|analogue]] of testosterone, works by acting as a [[potency (pharmacology)|potent]] and [[binding selectivity|specific]], [[competitive inhibition|competitive]] [[enzyme inhibitor|inhibitor]] of one of the two [[subtype polymorphism|subtype]]s of 5α-reductase, specifically the [[SRD5A2|type II]] [[isoenzyme]].<ref name="pmid19879888">{{cite journal |author=Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M |title=An overview on 5alpha-reductase inhibitors |journal=Steroids |volume=75 |issue=2 |pages=109–53 |date=February 2010 |pmid=19879888 |doi=10.1016/j.steroids.2009.10.005}}</ref> In other words, it binds to the enzyme and prevents [[endogenous]] [[enzyme substrate (biology)|substrate]]s such as testosterone from being metabolized. 5α-reductase type I and type II are responsible for approximately one-third and two-thirds of systemic DHT production, respectively.<ref name="PropeciaLabel">{{cite web | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020788s018lbl.pdf | title = PROPECIA® (finasteride) Tablets, 1 mg [US/FDA label] | format = PDF | work = | accessdate = 2012-05-22}}</ref> |
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As of 2016, Merck was a defendant in approximately 1,370 [[product liability]] lawsuits which had been filed by customers alleging they have experienced persistent sexual side effects following cessation of treatment with finasteride.<ref>{{cite news |date=4 February 2017 |title=Watch for these potential side effects in drug Trump reportedly takes for hair loss |newspaper=Miami Herald |url=https://www.miamiherald.com/news/nation-world/national/article130815949.html |access-date=9 December 2018 |vauthors=Marchalik D |archive-date=7 December 2018 |archive-url=https://web.archive.org/web/20181207171000/https://www.miamiherald.com/news/nation-world/national/article130815949.html |url-status=live }}</ref> Most cases were settled by 2018 when Merck paid a lump sum of $4.3 million USD to be distributed. {{asof|September 2019}}, 25 cases remained outstanding in the United States.<ref name="reu">{{Cite news |title=U.S. court let Merck hide secrets about popular drug's risks |language=en |website=Reuters |url=https://www.reuters.com/investigates/special-report/usa-courts-secrecy-propecia/ |access-date=25 March 2021 |quote=these legal briefs filed by plaintiffs' lawyers allege that in revisions to the drug's original 1997 label, Merck understated the number of men who experienced sexual symptoms in clinical trials, and how long those symptoms lasted. |archive-date=12 February 2020 |archive-url=https://web.archive.org/web/20200212182118/https://www.reuters.com/investigates/special-report/usa-courts-secrecy-propecia/ |url-status=live }}</ref> In 2019, Reuters reported that faulty redactions in court documents revealed allegations from plaintiffs that Merck had known of persistent side effects in their original clinical trials but chose not to disclose them in warning labels.<ref name="reu" /> |
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Other 5a-reductase substrates include [[progesterone]], [[androstenedione]], epi-testosterone, [[cortisol]], [[aldosterone]], and [[deoxycorticosterone]]. The entire physiologic effect of their reduction is unknown, but likely related to their excretion or is itself physiologic. Beyond being a catalyst in the [[rate-limiting step]] in testosterone reduction, 5alpha-reductase enzyme isoforms I and II reduce progesterone to dihydroprogesterone (DHP) and deoxycorticosterone to dihydrodeoxycorticosterone (DHDOC). In vitro and animal models suggest subsequent 3alpha-reduction of DHT, DHP and DHDOC lead to steroid metabolites with effect on cerebral function by enhancing [[gamma-aminobutyric acid]] GABAergic inhibition. These neuroactive steroid derivatives enhance GABA at GABA(A) receptors and have anticonvulsant, antidepressant and anxiolytic effects, and also alter sexual and alcohol related behavior.<ref name="pmid16834758"/> 5α-dihydrocortisol is present in the [[aqueous humor]] of the eye, is synthesized in the [[Lens (anatomy)|lens]], and might help make the aqueous humor itself.<ref name="Cort">{{cite journal |author=Weinstein BI, Kandalaft N, Ritch R, ''et al.'' |title=5 alpha-dihydrocortisol in human aqueous humor and metabolism of cortisol by human lenses in vitro |journal=Investigative Ophthalmology & Visual Science |volume=32 |issue=7 |pages=2130–5 |date=June 1991 |pmid=2055703 |url=http://www.iovs.org/cgi/pmidlookup?view=long&pmid=2055703}}</ref> [[Allopregnanolone]] and [[Tetrahydrodeoxycorticosterone|THDOC]] are [[neurosteroids]], with the latter having effects on the susceptibility of animals to seizures. 5α-dihydroaldosterone is a potent [[antidiuretic]] agent, although different from [[aldosterone]]. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium as follows:<ref name="Kenyon_1983">{{cite journal |author=Kenyon CJ, Brem AS, McDermott MJ, Deconti GA, Latif SA, Morris DJ |title=Antinatriuretic and kaliuretic activities of the reduced derivatives of aldosterone |journal=Endocrinology |volume=112 |issue=5 |pages=1852–6 |date=May 1983 |pmid=6403339 |doi=10.1210/endo-112-5-1852}}</ref> |
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==Overdose== |
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::: ''Substrate + NADPH + H+ → 5α-substrate + NADP+'' |
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Finasteride has been studied in humans at single doses of up to 400 mg and at continuous dosages of up to 80 mg/day for three months, without adverse effects observed.<ref name="Propecia FDA label" /><ref name="Proscar FDA label" /><ref name="pmid16719800">{{cite journal | vauthors = Frye SV | title = Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor | journal = Curr Top Med Chem | volume = 6 | issue = 5 | pages = 405–21 | date = 2006 | pmid = 16719800 | doi = 10.2174/156802606776743101 }}</ref> There is no specific recommended [[antidote]] for finasteride overdose.<ref name="Propecia FDA label" /><ref name="Proscar FDA label" /> |
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==Interactions== |
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5α-DHP is a major hormone in circulation of normal cycling and pregnant women.<ref name="pmid914969">{{cite journal |author=Milewich L, Gomez-Sanchez C, Crowley G, Porter JC, Madden JD, MacDonald PC |title=Progesterone and 5alpha-pregnane-3,20-dione in peripheral blood of normal young women: Daily measurements throughout the menstrual cycle |journal=The Journal of Clinical Endocrinology and Metabolism |volume=45 |issue=4 |pages=617–22 |date=October 1977 |pmid=914969 |doi=10.1210/jcem-45-4-617}}</ref> |
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No significant [[drug interaction]]s have been observed between finasteride and a limited selection of medications.<ref name="pmid7689728">{{cite journal | vauthors = Sudduth SL, Koronkowski MJ | title = Finasteride: the first 5α-reductase inhibitor | journal = Pharmacotherapy | volume = 13 | issue = 4 | pages = 309–25; discussion 325–9 | date = 1993 | pmid = 7689728 | doi = 10.1002/j.1875-9114.1993.tb02739.x | s2cid = 71103672 }}</ref> |
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==Pharmacology== |
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By inhibiting 5a-reductase, finasteride prevents conversion of testosterone to DHT by the type II isoenzyme, resulting in a decrease in serum DHT levels by about 65–70% and in prostate DHT levels by up to 85–90%,<ref name="pmid10765065">{{cite journal |author=Bartsch G, Rittmaster RS, Klocker H |title=Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia |journal=European Urology |volume=37 |issue=4 |pages=367–80 |date=April 2000 |pmid=10765065 |doi=10.1007/s00345-002-0248-5}}</ref> where [[gene expression|expression]] of the type II isoenzyme dominates. Unlike dual inhibitors of both isoenzymes of 5α-reductase which can reduce DHT levels in the entire body by more than 99%, finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the [[SRD5A1|5α-reductase type I]] isoenzyme, with 100-fold less affinity for I as compared to II.<ref name="PropeciaLabel" /> In addition to blocking the type II isoenzyme, finasteride competitively inhibits the 5β-reductase type II isoenzyme,<ref name="pmid19515843">{{cite journal |author=Drury JE, Di Costanzo L, Penning TM, Christianson DW |title=Inhibition of human steroid 5beta-reductase (AKR1D1) by finasteride and structure of the enzyme-inhibitor complex |journal=The Journal of Biological Chemistry |volume=284 |issue=30 |pages=19786–90 |date=July 2009 |pmid=19515843 |pmc=2740403 |doi=10.1074/jbc.C109.016931}}</ref> though this is not believed to affect androgen metabolism. |
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===Pharmacodynamics=== |
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By blocking DHT production, finasteride reduces androgen activity in the scalp. In the prostate, inhibition of 5α-reductase reduces prostate volume, which improves benign prostatic hyperplasia (BPH) and reduces risk of prostate cancer. 5α-reductase inhibition also reduces [[epididymis|epididymal]] weight, and decreases motility and normal morphology of spermatozoa in the epididymis.<ref name="pmid16476520">{{cite journal |author=Robaire B, Henderson NA |title=Actions of 5alpha-reductase inhibitors on the epididymis |journal=Molecular and Cellular Endocrinology |volume=250 |issue=1-2 |pages=190–5 |date=May 2006 |pmid=16476520 |doi=10.1016/j.mce.2005.12.044}}</ref> |
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Finasteride is a [[5α-reductase inhibitor]].<ref name="Propecia FDA label" /><ref name="LemkeWilliams2008" /> It is specifically a [[binding selectivity|selective]] [[enzyme inhibitor|inhibitor]] of the [[SRD5A2|type II]] and [[SRD5A3|III]] [[isoform]]s of the [[enzyme]].<ref name="LemkeWilliams2008" /><ref name="Yamana2010">{{cite journal | vauthors = Yamana K, Labrie F, Luu-The V | title = Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride | journal = Hormone Molecular Biology and Clinical Investigation | volume = 2 | issue = 3 | pages = 293–9 | date = August 2010 | pmid = 25961201 | doi = 10.1515/hmbci.2010.035 | s2cid = 28841145 }}</ref><ref name="pmid19879888">{{cite journal | vauthors = Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M | title = An overview on 5alpha-reductase inhibitors | journal = Steroids | volume = 75 | issue = 2 | pages = 109–53 | date = February 2010 | pmid = 19879888 | doi = 10.1016/j.steroids.2009.10.005 | s2cid = 44363501 }}</ref> By inhibiting these two isozymes of 5α-reductase, finasteride reduces the formation of the [[potency (pharmacology)|potent]] [[androgen]] [[dihydrotestosterone]] (DHT) from its [[precursor (biochemistry)|precursor]] [[testosterone]] in certain [[tissue (biology)|tissue]]s in the body such as the [[prostate gland]], [[skin]], and [[hair follicle]]s.<ref name="LemkeWilliams2008" /><ref name="Azz">{{cite journal |vauthors=Azzouni F, Godoy A, Li Y, Mohler J | title = The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases | journal = Adv Urol | volume = 2012 | pages = 1–18 | year = 2012 | pmid = 22235201 | pmc = 3253436 | doi = 10.1155/2012/530121 | doi-access = free }}</ref> As such, finasteride is a type of [[antiandrogen]], or more specifically, an [[androgen synthesis inhibitor]].<ref name="Preedy2012">{{cite book|vauthors=Preedy VR|title=Handbook of Hair in Health and Disease|url=https://books.google.com/books?id=7N3nEX6eL_MC&pg=PA89|year=2012|publisher=Springer Science & Business Media|isbn=978-90-8686-728-8|pages=89–|access-date=6 May 2018|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031743/https://books.google.com/books?id=7N3nEX6eL_MC&pg=PA89|url-status=live}}</ref><ref name="Wu2012">{{cite book|vauthors=Wu JJ|title=Comprehensive Dermatologic Drug Therapy E-Book|url=https://books.google.com/books?id=Tqpsm5WKKlcC&pg=PA361|date=18 October 2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-3801-4|pages=361–|access-date=6 May 2018|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031703/https://books.google.com/books?id=Tqpsm5WKKlcC&pg=PA361|url-status=live}}</ref> However, some authors do not define finasteride as an "antiandrogen," a term which can refer more specifically to antagonists of the [[androgen receptor]].<ref name="ClapauchWeiss2017">{{cite book| vauthors = Clapauch R, Weiss RV, Rech CM |title=Testosterone|chapter=Testosterone and Women|year=2017|pages=319–351|publisher=Springer |doi=10.1007/978-3-319-46086-4_17|quote=Finasteride is not actually an antiandrogen but a 5α-reductase inhibitor.|isbn=978-3-319-46084-0}}</ref> |
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Finasteride results in a decrease of circulating DHT levels by about 65–70% with an oral dosage of 5 mg/day and of DHT levels in the prostate gland by up to 80–90% with an oral dosage of 1 or 5 mg/day.<ref name="Yamana2010" /><ref name="pmid10765065">{{cite journal|vauthors=Bartsch G, Rittmaster RS, Klocker H|date=April 2000|title=Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia|journal=European Urology|volume=37|issue=4|pages=367–80|doi=10.1159/000020181|pmid=10765065|s2cid=25793400}}</ref><ref name="pmid29379733">{{cite journal | vauthors = Kim EH, Brockman JA, Andriole GL | title = The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia | journal = Asian Journal of Urology | volume = 5 | issue = 1 | pages = 28–32 | date = January 2018 | pmid = 29379733 | pmc = 5780290 | doi = 10.1016/j.ajur.2017.11.005 }}</ref> In parallel, circulating levels of testosterone increase by approximately 10%, while local concentrations of testosterone in the prostate gland increase by about 7-fold and local testosterone levels in hair follicles increase by around 27–53%.<ref name="pmid7505051">{{cite journal | vauthors = Rittmaster RS | title = Finasteride | journal = N. Engl. J. Med. | volume = 330 | issue = 2 | pages = 120–5 | date = January 1994 | pmid = 7505051 | doi = 10.1056/NEJM199401133300208 }}</ref><ref name="pmid15102575">{{cite journal | vauthors = Libecco JF, Bergfeld WF | title = Finasteride in the treatment of alopecia | journal = Expert Opin Pharmacother | volume = 5 | issue = 4 | pages = 933–40 | date = April 2004 | pmid = 15102575 | doi = 10.1517/14656566.5.4.933 | s2cid = 24296644 }}</ref> An oral dosage of finasteride of only 0.2 mg/day has been found to achieve near-maximal suppression of DHT levels (68.6% for 0.2 mg/day relative to 72.2% for 5 mg/day).<ref name="pmid15102575" /><ref name="pmid12894990">{{cite journal | vauthors = Shapiro J, Kaufman KD | title = Use of finasteride in the treatment of men with androgenetic alopecia (male pattern hair loss) | journal = J. Investig. Dermatol. Symp. Proc. | volume = 8 | issue = 1 | pages = 20–3 | date = June 2003 | pmid = 12894990 | doi = 10.1046/j.1523-1747.2003.12167.x | doi-access = free }}</ref> Finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the [[SRD5A1|5α-reductase type I]] isoenzyme, with more than 100-fold less inhibitory potency for type I as compared to type II ({{abbrlink|IC<sub>50</sub>|Half-maximal inhibitory concentration}} = 313 nM and 11 nM, respectively).<ref name="Propecia FDA label" /><ref name="LemkeWilliams2008" /> This is in contrast to inhibitors of all three isoenzymes of 5α-reductase like [[dutasteride]], which can reduce DHT levels in the entire body by more than 99%.<ref name="Yamana2010" /> In addition to inhibiting 5α-reductase, finasteride has also been found to competitively inhibit [[5β-reductase]] (AKR1D1).<ref name="pmid19515843">{{cite journal | vauthors = Drury JE, Di Costanzo L, Penning TM, Christianson DW |author4-link=David W. Christianson| title = Inhibition of human steroid 5beta-reductase (AKR1D1) by finasteride and structure of the enzyme-inhibitor complex | journal = The Journal of Biological Chemistry | volume = 284 | issue = 30 | pages = 19786–90 | date = July 2009 | pmid = 19515843 | pmc = 2740403 | doi = 10.1074/jbc.C109.016931 | doi-access = free }}</ref> However, its affinity for the enzyme is substantially less than for 5α-reductase (an order of magnitude less than for 5α-reductase ''type I'') and hence is unlikely to be of clinical significance.<ref name="pmid19515843" /> |
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===Cause of mood-related and sexual side effects=== |
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DHT, and [[neuroactive steroid]]s (NAs) such as [[allopregnanolone]] (ALLO) and [[tetrahydrodeoxycorticosterone]] (THDOC)—potent [[positive allosteric modulator]]s of the [[GABAA receptor|GABA<sub>A</sub> receptor]] (the same [[mechanism of action|site of action]] of [[euphoriant]] and [[anxiolytic]] [[drug]]s like [[benzodiazepine]]s and [[drinking alcohol|alcohol]])—are important [[endogenous]] [[neuroregulator]]s that have been shown to possess powerful [[antidepressant]] and [[anxiolytic]] effects as well as to play a positive role in [[sexual function]].<ref name="pmid16834758" /><ref name="pmid21122055">{{cite journal |author=Römer B, Gass P |title=Finasteride-induced depression: new insights into possible pathomechanisms |journal=Journal of Cosmetic Dermatology |volume=9 |issue=4 |pages=331–2 |date=December 2010 |pmid=21122055 |doi=10.1111/j.1473-2165.2010.00533.x}}</ref><ref name="pmid22164129">{{cite journal |author=Gunn BG, Brown AR, Lambert JJ, Belelli D |title=Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress |journal=Frontiers in Neuroscience |volume=5 |issue= |pages=131 |year=2011 |pmid=22164129 |pmc=3230140 |doi=10.3389/fnins.2011.00131}}</ref> Their [[biosynthesis]] is dependent on both isoforms of 5α-reductase, and accordingly, finasteride has been shown to reduce their formation in the body.<ref name="pmid2538808">{{cite journal |author=Vermeulen A, Giagulli VA, De Schepper P, Buntinx A, Stoner E |title=Hormonal effects of an orally active 4-azasteroid inhibitor of 5 alpha-reductase in humans |journal=The Prostate |volume=14 |issue=1 |pages=45–53 |year=1989 |pmid=2538808 |doi=10.1002/pros.2990140106}}</ref><ref name="pmid9918575">{{cite journal |author=Kokate TG, Banks MK, Magee T, Yamaguchi S, Rogawski MA |title=Finasteride, a 5alpha-reductase inhibitor, blocks the anticonvulsant activity of progesterone in mice |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=288 |issue=2 |pages=679–84 |date=February 1999 |pmid=9918575 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9918575}}</ref><ref name="pmid19655698">{{cite journal |author=Dusková M, Hill M, Hanus M, Matousková M, Stárka L |title=Finasteride treatment and neuroactive steroid formation |journal=Prague Medical Report |volume=110 |issue=3 |pages=222–30 |year=2009 |pmid=19655698}}</ref> As such, this effect of finasteride is a likely cause of the emotional and sexual side effects associated with the drug.<ref name="pmid16834758" /><ref name="pmid21122055" /> |
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As of 2012, the tissues in which the different isozymes of 5α-reductase are expressed are not fully clear.<ref name=Azz /> This is because different investigators have obtained varying results with different [[reagent]]s, methods, and tissues examined.<ref name=Azz /> However, the different isozymes of 5α-reductase appear to be widely expressed, with notable tissues including the prostate gland, [[seminal vesicle]]s, [[testicle|testes]], [[epididymis|epididymides]], skin, hair follicles, [[liver]], [[kidney]]s, and [[brain]], among others.<ref name=Azz /> |
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==Vehicle== |
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Drug trade names include Propecia and Proscar, the former marketed for male pattern baldness (MPB) and the latter for benign prostatic hyperplasia (BPH), both are products of [[Merck & Co]]. There is 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck's patent on finasteride for the treatment of BPH expired on June 19, 2006.<ref>[http://www.rxsolutions.com/c/rxnews/rxnews_view.asp?Article=674&type=19 Primary Patent Expirations for Selected High Revenue Drugs]</ref> Merck was awarded a separate patent for the use of finasteride to treat MPB. This patent is set to expire in November 2013.<ref>[http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020788&Product_No=001&table1=OB_Rx fda.gov | Patent Expiration for Propecia]</ref> |
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By inhibiting 5α-reductase and thus preventing DHT production, finasteride reduces androgen signaling in tissues like the prostate gland and the scalp. In the prostate, this reduces prostate volume, which improves BPH and reduces risk of prostate cancer. Finasteride reduces prostate volume by 20 to 30% in men with benign prostatic hyperplasia.<ref name="BostwickCheng2014">{{cite book | vauthors = Bostwick DG, Cheng L | title = Urologic Surgical Pathology E-Book | url = https://books.google.com/books?id=wrHQAgAAQBAJ&pg=PA402 | date = 24 January 2014 | publisher = Elsevier Health Sciences | isbn = 978-0-323-08619-6 | pages = 402– }}</ref> Inhibition of 5α-reductase also reduces [[epididymis|epididymal]] weight, and decreases motility and normal morphology of spermatozoa in the epididymis.<ref name="pmid16476520">{{cite journal | vauthors = Robaire B, Henderson NA | title = Actions of 5alpha-reductase inhibitors on the epididymis | journal = Molecular and Cellular Endocrinology | volume = 250 | issue = 1–2 | pages = 190–5 | date = May 2006 | pmid = 16476520 | doi = 10.1016/j.mce.2005.12.044 | s2cid = 53464391 }}</ref> |
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Some studies have shown that the dose of finasteride needed to treat male pattern baldness may be smaller than 1 mg.<ref name=PropeciaFDA1>{{cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20788_PROPECIA%20TABLETS,%201MG_CORRES.PDF|format=PDF|publisher=U.S. Food and Drug Administration|title=Center for Drug Evaluation and Research, Application Number NDA 20–788}}</ref> Petitions to the FDA to re-examine the approved dosage in light of the statistical evidence and possible long-term risks,<ref name=PropeciaFDA2>{{cite web|url=http://www.fda.gov/ohrms/dockets/dailys/00/Dec00/121800/pav0001.pdf|format=PDF|publisher=U.S. Food and Drug Administration|title=Letter to Dr. Sherman Frankel, University of Pennsylvania}}</ref> were met with the response that a study had shown increased effect of a 1 mg dose compared to 0.2 mg without added risks; the same study also concluded that doses of ''0.01'' mg per day were found to be ineffective in treating hair loss.<ref name=PropeciaFDA2/> |
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[[Neurosteroid]]s like [[3α-androstanediol]] (derived from DHT) and [[allopregnanolone]] (derived from [[progesterone]]) activate the [[GABAA receptor|GABA<sub>A</sub> receptor]] in the [[brain]]; because finasteride prevents the formation of neurosteroids, it functions as a [[neurosteroidogenesis inhibitor]] and may contribute to a reduction of GABA<sub>A</sub> activity. Reduction of GABA<sub>A</sub> receptor activation by these neurosteroids has been implicated in [[depression (mood)|depression]], [[anxiety]], and [[sexual dysfunction]].<ref name="pmid16834758">{{cite journal | vauthors = Finn DA, Beadles-Bohling AS, Beckley EH, Ford MM, Gililland KR, Gorin-Meyer RE, Wiren KM | title = A new look at the 5alpha-reductase inhibitor finasteride | journal = CNS Drug Reviews | volume = 12 | issue = 1 | pages = 53–76 | year = 2006 | pmid = 16834758 | pmc = 6741762 | doi = 10.1111/j.1527-3458.2006.00053.x }}</ref><ref name="pmid21122055">{{cite journal | vauthors = Römer B, Gass P | title = Finasteride-induced depression: new insights into possible pathomechanisms | journal = Journal of Cosmetic Dermatology | volume = 9 | issue = 4 | pages = 331–2 | date = December 2010 | pmid = 21122055 | doi = 10.1111/j.1473-2165.2010.00533.x | s2cid = 24328589 | url = https://zenodo.org/record/896024 | access-date = 26 May 2019 | archive-date = 2 December 2020 | archive-url = https://web.archive.org/web/20201202011005/https://zenodo.org/record/896024 | url-status = live }}</ref><ref name="pmid22164129">{{cite journal | vauthors = Gunn BG, Brown AR, Lambert JJ, Belelli D | title = Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress | journal = Frontiers in Neuroscience | volume = 5 | pages = 131 | year = 2011 | pmid = 22164129 | pmc = 3230140 | doi = 10.3389/fnins.2011.00131 | doi-access = free }}</ref> |
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Finasteride is [[lipophilic]],<ref name="micro">{{cite journal |author=Azeem A, Khan ZI, Aqil M, Ahmad FJ, Khar RK, Talegaonkar S |title=Microemulsions as a surrogate carrier for dermal drug delivery |journal=Drug Development and Industrial Pharmacy |volume=35 |issue=5 |pages=525–47 |date=May 2009 |pmid=19016057 |doi=10.1080/03639040802448646}}</ref> and development of a liposomal system of finasteride for [[Topical medication|topical application]] has been a subject of recent study.<ref>{{cite journal |author=Kumar R, Singh B, Bakshi G, Katare OP |title=Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation |journal=Pharmaceutical Development and Technology |volume=12 |issue=6 |pages=591–601 |year=2007 |pmid=18161632 |doi=10.1080/10837450701481181}}</ref> Topical formulations show some effect in reversal of androgenic effects on hair follicles,<ref name="Topical">{{cite journal |author=Ye F, Imamura K, Imanishi N, Rhodes L, Uno H |title=Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats |journal=Skin Pharmacology |volume=10 |issue=5-6 |pages=288–97 |year=1997 |pmid=9449168}}</ref> as well as in hirsutism.<ref>{{cite journal |author=Póltorak JL |title=[Bile duct calculosis] |language=Polish |journal=Polski Tygodnik Lekarski |volume=31 |issue=4 |pages=145–8 |date=January 1976 |pmid=1250761}}</ref> More recent studies have looked at microemulsions<ref name="micro"/> and liquid crystalline [[nanoparticles]] for topical finasteride delivery. In the latter, addition of glycerol, propylene glycol, and polyethylene glycol 400, increased finasteride permeation, while addition of [[oleic acid]] made it decrease.<ref>{{cite journal |author=Madheswaran T, Baskaran R, Thapa RK, ''et al.'' |title=Design and in vitro evaluation of finasteride-loaded liquid crystalline nanoparticles for topical delivery |journal=AAPS PharmSciTech |volume=14 |issue=1 |pages=45–52 |date=March 2013 |pmid=23207960 |pmc=3581658 |doi=10.1208/s12249-012-9888-y}}</ref> Topical finasteride in combination with topical minoxidil is more effective than topical minoxidil alone.<ref name=Combined1>{{cite journal |author=Tanglertsampan C |title=Efficacy and safety of 3% minoxidil versus combined 3% minoxidil / 0.1% finasteride in male pattern hair loss: a randomized, double-blind, comparative study |journal=Journal of the Medical Association of Thailand |volume=95 |issue=10 |pages=1312–6 |date=October 2012 |pmid=23193746}}</ref> Small studies of topical finasteride formulations in combination with other drugs have also been found effective.<ref name=Combined2>{{cite journal |author=Rafi AW, Katz RM |title=Pilot Study of 15 Patients Receiving a New Treatment Regimen for Androgenic Alopecia: The Effects of Atopy on AGA |journal=ISRN Dermatology |volume=2011 |issue= |pages=241953 |year=2011 |pmid=22363845 |pmc=3262531 |doi=10.5402/2011/241953}}</ref> Surfactants have been shown to aid topical absorption.<ref>{{cite journal |author=Javadzadeh Y, Shokri J, Hallaj-Nezhadi S, Hamishehkar H, Nokhodchi A |title=Enhancement of percutaneous absorption of finasteride by cosolvents, cosurfactant and surfactants |journal=Pharmaceutical Development and Technology |volume=15 |issue=6 |pages=619–25 |date=December 2010 |pmid=19929166 |doi=10.3109/10837450903397610}}</ref> Topical finasteride gel has been shown an effective route of administration.<ref>{{cite journal |author=Hajheydari Z, Akbari J, Saeedi M, Shokoohi L |title=Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia |journal=Indian Journal of Dermatology, Venereology and Leprology |volume=75 |issue=1 |pages=47–51 |year=2009 |pmid=19172031 |url=http://www.ijdvl.com/article.asp?issn=0378-6323;year=2009;volume=75;issue=1;spage=47;epage=51;aulast=Hajheydari}}</ref> |
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In accordance with finasteride being a potent 5α-reductase inhibitor but a weak inhibitor of 5β-reductase, the medication decreases circulating levels of 5α-reduced steroids like allopregnanolone but does not reduce concentrations of 5β-reduced steroids like [[pregnanolone]].<ref name="pmid21176115">{{cite journal | vauthors = Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML | title = Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients | journal = J Sex Med | volume = 8 | issue = 3 | pages = 872–84 | date = March 2011 | pmid = 21176115 | doi = 10.1111/j.1743-6109.2010.02157.x | url = }}</ref><ref name="pmid19655698">{{cite journal | vauthors = Dusková M, Hill M, Hanus M, Matousková M, Stárka L | title = Finasteride treatment and neuroactive steroid formation | journal = Prague Med Rep | volume = 110 | issue = 3 | pages = 222–30 | date = 2009 | pmid = 19655698 | doi = | url = }}</ref><ref name="pmid25961975">{{cite journal | vauthors = Dušková M, Hill M, Stárka L | title = The influence of low dose finasteride, a type II 5α-reductase inhibitor, on circulating neuroactive steroids | journal = Horm Mol Biol Clin Investig | volume = 1 | issue = 2 | pages = 95–102 | date = January 2010 | pmid = 25961975 | doi = 10.1515/HMBCI.2010.010 | s2cid = 28578077 | url = }}</ref> Pregnanolone acts as a potent GABA<sub>A</sub> receptor positive allosteric modulator similarly to allopregnanolone.<ref name="pmid15248811">{{cite journal | vauthors = Reddy DS | title = Pharmacology of endogenous neuroactive steroids | journal = Crit Rev Neurobiol | volume = 15 | issue = 3–4 | pages = 197–234 | date = 2003 | pmid = 15248811 | doi = 10.1615/critrevneurobiol.v15.i34.20 | url = }}</ref> |
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==Chemical synthesis== |
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[[File:Propecia box and tablet.jpg|thumb|left|Propecia (finasteride) 1 mg tablets]] |
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[[File:Finpecia from India is Cheap Propecia.jpg|thumb|right|Propecia 1 mg & [[generic drug|Finpecia]] 1 mg tablets]] |
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===Pharmacokinetics=== |
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Finasteride is synthesized from [[progesterone]]:<ref name=pmid3783591>{{cite journal |author=Rasmusson GH, Reynolds GF, Steinberg NG, ''et al.'' |title=Azasteroids: structure-activity relationships for inhibition of 5 alpha-reductase and of androgen receptor binding |journal=Journal of Medicinal Chemistry |volume=29 |issue=11 |pages=2298–315 |date=November 1986 |pmid=3783591 |doi=10.1021/jm00161a028}}</ref><ref name=ja00218a062>{{Cite journal | doi = 10.1021/ja00218a062 | title = Silylation-mediated oxidation of 4-aza-3-ketosteroids with DDQ proceeds via DDQ-substrate adducts |date=May 1988 | author = Bhattacharya A, Dimichele LM, Dolling U, Douglas AW, Grabowski EJJ | journal = Journal of the American Chemical Society | volume=110 | pages = 3318–9 }}</ref> |
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The mean [[oral administration|oral]] [[bioavailability]] of finasteride is approximately 65%.<ref name="LemkeWilliams2008" /> The [[absorption (pharmacokinetics)|absorption]] of finasteride is not affected by food.<ref name="Propecia FDA label" /><ref name="Proscar FDA label" /> At [[steady-state]] with 1 mg/day finasteride, mean [[Cmax (pharmacology)|peak]] concentrations of finasteride were 9.2 ng/mL (25 nmol/L).<ref name="Propecia FDA label" /> Conversely, following a single 5 mg dose of finasteride, mean peak levels of finasteride were 37 ng/mL (99 nmol/L), and plasma concentrations increased by 47–54% following 2.5 weeks of continued daily administration.<ref name="Proscar FDA label" /> The [[volume of distribution]] of finasteride is 76 L.<ref name="LemkeWilliams2008" /> Its [[plasma protein binding]] is 90%.<ref name="LemkeWilliams2008" /> The drug has been found to cross the [[blood–brain barrier]], whereas levels in [[semen]] were found to be undetectable.<ref name="LemkeWilliams2008" /> |
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Finasteride is extensively [[metabolism|metabolized]] in the [[liver]], first by [[hydroxylation]] via [[CYP3A4]] and then by [[aldehyde dehydrogenase]].<ref name="LemkeWilliams2008" /> It has two major [[metabolite]]s, which are the ''tert''-[[butyl group|butyl]] [[side chain]] monohydroxylated and [[carboxylic acid|monocarboxylic acid]] metabolites.<ref name="LemkeWilliams2008" /> These metabolites show approximately 20% of the inhibitory activity of finasteride on 5α-reductase.<ref name="LemkeWilliams2008" /> Hence, the metabolites of finasteride are not particularly active.<ref name="LemkeWilliams2008" /> The drug has a [[terminal half-life]] of 5 to 6 hours in adult men (18–60 years of age) and a terminal half-life of 8 hours or more in elderly men (more than 70 years of age).<ref name="LemkeWilliams2008" /> It is [[elimination (pharmacology)|eliminated]] as its metabolites 57% in the [[feces]] and 40% in the [[urine]].<ref name="LemkeWilliams2008" /> |
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[[File:Finasteride Synth.png|thumb|1000px|center|Preparation of finasteride<ref name=pmid3783591/><ref name=ja00218a062/>]] |
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==Chemistry== |
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{{See also|List of 5α-reductase inhibitors}} |
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Finasteride, also known as 17β-(''N''-tert-butylcarbamoyl)-4-aza-5α-androst-1-en-3-one, is a [[synthetic compound|synthetic]] [[androstane]] [[steroid]] and [[4-azasteroid]].<ref name="pmid7689728" /><ref name="pmid8117686">{{cite journal | vauthors = Tian G, Stuart JD, Moss ML, Domanico PL, Bramson HN, Patel IR, Kadwell SH, Overton LK, Kost TA, Mook RA | title = 17 beta-(N-tert-butylcarbamoyl)-4-aza-5 alpha-androstan-1-en-3-one is an active site-directed slow time-dependent inhibitor of human steroid 5 alpha-reductase 1 | journal = Biochemistry | volume = 33 | issue = 8 | pages = 2291–6 | year = 1994 | pmid = 8117686 | doi = 10.1021/bi00174a041}}</ref> It is an [[structural analogue|analogue]] of androgen [[steroid hormone]]s like testosterone and DHT.<ref name="pmid7689728" /> As an unconjugated steroid, finasteride is a highly [[lipophilic]] compound.<ref name="pmid7689728" /><ref name="micro">{{cite journal | vauthors = Azeem A, Khan ZI, Aqil M, Ahmad FJ, Khar RK, Talegaonkar S | title = Microemulsions as a surrogate carrier for dermal drug delivery | journal = Drug Development and Industrial Pharmacy | volume = 35 | issue = 5 | pages = 525–47 | date = May 2009 | pmid = 19016057 | doi = 10.1080/03639040802448646 | s2cid = 205563538 }}</ref> |
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==History== |
==History== |
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In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on birth defects. She reported on a group of [[intersex]] children in the [[Caribbean]] who appeared sexually [[Ambiguity|ambiguous]] at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic |
In 1942, James Hamilton observed that prepubertal castration prevents the later development of male pattern baldness in mature men.<ref>{{cite journal | vauthors = Hamilton J | year = 1942 | title = Male hormone stimulation is prerequisite and an incitant in common baldness | journal = American Journal of Anatomy | volume = 71 | issue = 3| pages = 451–480 | doi = 10.1002/aja.1000710306 }}</ref> In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on birth defects. She reported on a group of [[intersex]] children in the [[Caribbean]] who appeared sexually [[Ambiguity|ambiguous]] at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic after onset of puberty. These children, despite being raised as girls until puberty, were generally heterosexual, and were termed "[[Guevedoces]]" by their local community, which means "penis at twelve" in Spanish.<ref>{{Cite news|url=https://www.bbc.co.uk/news/magazine-34290981|title=The extraordinary case of the Guevedoces|date=20 September 2015|work=BBC News|access-date=3 September 2018|archive-date=13 August 2020|archive-url=https://web.archive.org/web/20200813070330/https://www.bbc.co.uk/news/magazine-34290981|url-status=live}}</ref> Her research group found these children shared a [[genetic mutation]], causing [[5-alpha-reductase deficiency|deficiency of the 5α-reductase enzyme]] and male hormone [[dihydrotestosterone]] (DHT), which was found to have been the etiology behind abnormalities in male sexual development. Upon maturation, these individuals were observed to have smaller prostates which were underdeveloped, and were also observed to lack incidence of male pattern baldness.<ref name="pmid4432067">{{cite journal | vauthors = Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE | title = Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism | journal = Science | volume = 186 | issue = 4170 | pages = 1213–5 | date = December 1974 | pmid = 4432067 | doi = 10.1126/science.186.4170.1213 | s2cid = 36427689 | bibcode = 1974Sci...186.1213I }}</ref><ref>{{cite journal | vauthors = Isfort AH, Emerick JE, Paz RA | series = News & Perspective Drugs & Diseases CME & Education Academy Consult, Drugs & Diseases > Pediatrics: General Medicine | title = 5-Alpha-Reductase Deficiency | date = 11 November 2016 | journal = WebMD | url = http://emedicine.medscape.com/article/924291-overview#showall | access-date = 25 October 2014 | archive-date = 6 August 2020 | archive-url = https://web.archive.org/web/20200806073933/https://emedicine.medscape.com/article/924291-overview#showall | url-status = live }}</ref> |
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In 1975, copies of Imperato-McGinley's presentation were seen by [[P. Roy Vagelos]], who was then serving as Merck's basic-research chief. He was intrigued by the notion that decreased levels of DHT led to the development of smaller prostates. Dr. Vagelos then sought to create a drug which could mimic the condition found in these children |
In 1975, copies of Imperato-McGinley's presentation were seen by [[P. Roy Vagelos]], who was then serving as [[Merck & Co.|Merck]]'s basic-research chief. He was intrigued by the notion that decreased levels of DHT led to the development of smaller prostates. Dr. Vagelos then sought to create a drug which could mimic the condition found in these children to treat older men who had benign prostatic hyperplasia.<ref>{{cite news | url = https://www.nytimes.com/1992/02/16/business/keeping-the-pipeline-filled-at-merck.html | work = The New York Times | vauthors = Freudenheim M | title = Keeping the Pipeline Filled at Merck | date = 16 February 1992 | access-date = 16 February 2017 | archive-date = 14 March 2017 | archive-url = https://web.archive.org/web/20170314051749/http://www.nytimes.com/1992/02/16/business/keeping-the-pipeline-filled-at-merck.html | url-status = live }}</ref> |
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Finasteride was developed by Merck under the code name MK-906.<ref name="pmid7689728" /> A team led by chemist Gary Rasmusson and biologist Jerry Brooks developed potential 5α-reductase inhibitors based on transition state inhibitors, using an iterative process of molecular design, testing, and redesign.<ref name="Cordes2014">{{cite book | vauthors = Cordes EH | title = Hallelujah Moments: Tales of Drug Discovery | url = https://books.google.com/books?id=_G9VAgAAQBAJ | year = 2014 | publisher = Oxford University Press | isbn = 9780199337149 | access-date = 21 June 2020 | archive-date = 10 January 2023 | archive-url = https://web.archive.org/web/20230110031704/https://books.google.com/books?id=_G9VAgAAQBAJ | url-status = live }}</ref> In 1992, finasteride (5 mg) was approved by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) for treatment of BPH, which Merck marketed under the brand name Proscar. Rasmusson and Brooks were awarded IPO's "Inventor of the Year" award in 1993 for their work on finasteride.<ref name=IPOInventor>{{cite web |title=Past Inventor of the Year Award Winners |url=https://www.ipoef.org/past-ioy-winners |website=ipoef.org |publisher=Intellectual Property Owners Education Foundation |access-date=21 June 2020 |archive-date=25 June 2020 |archive-url=https://web.archive.org/web/20200625183234/https://www.ipoef.org/past-ioy-winners/ |url-status=live }}</ref> In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg) for treatment of male pattern hair loss, which was marketed under the brand name Propecia.<ref name="BurgerAbraham2003">{{cite book | vauthors = Burger A, Abraham DJ | title = Burger's Medicinal Chemistry and Drug Discovery, Autocoids, Diagnostics, and Drugs from New Biology | url = https://books.google.com/books?id=25ZUAAAAMAAJ | date = 20 February 2003 | publisher = Wiley | isbn = 978-0-471-37030-7 | page = 439 | access-date = 4 December 2017 | archive-date = 10 January 2023 | archive-url = https://web.archive.org/web/20230110031744/https://books.google.com/books?id=25ZUAAAAMAAJ | url-status = live }}</ref> It was the first 5α-reductase inhibitor to be introduced and was followed by [[dutasteride]] in 2001.<ref name="Doherty2003">{{cite book | vauthors = Doherty AM | title = Annual Reports in Medicinal Chemistry | url = https://books.google.com/books?id=ECfQ6D5JLusC&pg=PA353 | year = 2003 | publisher = Academic Press | isbn = 978-0-12-040538-1 | pages = 353– | access-date = 4 December 2017 | archive-date = 10 January 2023 | archive-url = https://web.archive.org/web/20230110031703/https://books.google.com/books?id=ECfQ6D5JLusC&pg=PA353 | url-status = live }}</ref> The first study of finasteride in the treatment of hirsutism in women was published in 1994.<ref name="pmid9420861">{{cite journal | vauthors = Diamanti-Kandarakis E, Tolis G, Duleba AJ | title = Androgens and therapeutic aspects of antiandrogens in women | journal = J. Soc. Gynecol. Investig. | volume = 2 | issue = 4 | pages = 577–92 | date = 1995 | pmid = 9420861 | doi = 10.1177/107155769500200401 | s2cid = 32242838 }}</ref> |
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In 1992, finasteride (5 mg) was approved by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) for treatment of [[benign prostatic hyperplasia]] (BPH), which [[Merck & Co|Merck]] marketed under the brand name ''Proscar''. |
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==Society and culture== |
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In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg) for treatment of [[male pattern baldness]] (MPB), which was marketed under the brand name ''Propecia''. |
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===Generic names=== |
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''Finasteride'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}, while ''finastéride'' is its {{abbrlink|DCF|Dénomination Commune Française}}.<ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PP1|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|page=443}}</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=PA121|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=121–}}</ref><ref name="BycroftPayne2013">{{cite book|vauthors=Bycroft BW, Payne DJ|title=Dictionary of Antibiotics and Related Substances: with CD-ROM, Second Edition|url=https://books.google.com/books?id=x0hZDwAAQBAJ&pg=PA816|date=9 August 2013|publisher=CRC Press|isbn=978-1-4822-8215-3|pages=816–|access-date=6 May 2018|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031704/https://books.google.com/books?id=x0hZDwAAQBAJ&pg=PA816|url-status=live}}</ref><ref name="Drugs.com">{{Cite web | url=https://www.drugs.com/international/finasteride.html | title=Finasteride | access-date=6 December 2017 | archive-date=8 April 2019 | archive-url=https://web.archive.org/web/20190408115008/https://www.drugs.com/international/finasteride.html | url-status=live }}</ref> It is also known by its former developmental code names ''MK-906'', ''YM-152'', and ''L-652,931''.<ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="BycroftPayne2013" /><ref name="Drugs.com" /> |
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===Brand names=== |
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{| class="wikitable" style="margin:auto 1em auto 1em; float:left;" |
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Finasteride is marketed primarily under the brand names Propecia, for pattern hair loss, and Proscar, for BPH, both of which are products of [[Merck & Co]].<ref name="Drugs.com" /> There is 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck's patent on finasteride for the treatment of BPH expired in June 2006.<ref>{{cite web | archive-url = https://web.archive.org/web/20080321140432/http://www.rxsolutions.com/c/rxnews/rxnews_view.asp?Article=674&type=19 | archive-date = 21 March 2008 | url-status = dead | url = http://www.rxsolutions.com/c/rxnews/rxnews_view.asp?Article=674&type=19 | title = Primary Patent Expirations for Selected High Revenue Drugs | work = RxNews | publisher = Prescription Solutions }}</ref> Merck was awarded a separate patent for the use of finasteride to treat pattern hair loss and it expired in November 2013.<ref>{{cite web | url = http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020788&Product_No=001&table1=OB_Rx | author = FDA | title = Patent Expiration for Propecia | work = Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations | access-date = 17 August 2007 | archive-date = 26 October 2016 | archive-url = https://web.archive.org/web/20161026171214/http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020788&Product_No=001&table1=OB_Rx | url-status = live }}</ref> Finasteride is also marketed under a variety of other brand names throughout the world.<ref name="Drugs.com" /> |
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|- |
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! [[Epristeride]] || 4-MA || [[Turosteride]] || [[Lapisteride]] || [[Izonsteride]] |
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|- |
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| <center>[[Image:Epristeride.svg|200px|Epristeride]]</center> || <center>[[Image:4-MA steroid.svg|200px|4-MA]] || <center>[[Image:Turosteride.svg|200px|Turosteride]] || <center>[[Image:Lapisteride.svg|200px|Lapisteride]] || <center>[[Image:Izonsteride.svg|200px|Izonsteride]]</center> |
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|}{{-}} |
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{{colbegin|2}} |
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* [[Dutasteride]], related 5α-reductase inhibitor ([[isozyme]] I, II and III) |
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* [[Bexlosteride]] 5-α reductase inhibitor ([[isozyme]] I selective). |
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* [[Epristeride]] ([[SKF-105657]]) ([[SmithKline Beecham]]) |
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* [[Turosteride]] (FCE-26,073) |
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* 4-MA steroid not amp |
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* [[FCE 28260]] |
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* [[Izonsteride]] (LY-320,236) |
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* [[Lapisteride]] (INN; CS-891) |
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* [[Galeterone]] (TOK-001 or VN/124-1) |
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* [[Abiraterone]] |
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* [[Ganoderic acid]] |
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* [[Minoxidil]] |
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{{colend}} |
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===Athletics=== |
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{{cquote|The two isozymes, usually called Type I and Type II, exhibit differences in their biochemical properties, genetics and pharmacology. Both isozymes are now the subject of considerable research and it has been found that Type I is more prevalent in the scalp, and that Type II is more prevalent in the prostate.<ref>{{US Patent|5629007}}</ref>}} |
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From 2005 to 2009, the [[World Anti-Doping Agency]] banned finasteride because it was discovered that the drug could be used to mask [[anabolic steroids|steroid]] abuse.<ref>{{cite news | url=https://query.nytimes.com/gst/fullpage.html?sec=health&res=9F02E2DB153FF93AA25752C0A9609C8B63&n=Top%2fReference%2fTimes%20Topics%2fSubjects%2fO%2fOlympic%20Games | work=The New York Times | title=Skin Deep; Fighting Baldness, and Now an Olympic Ban | vauthors=Sandomir R | date=19 January 2006 | access-date=2 May 2010 | archive-date=4 December 2017 | archive-url=https://web.archive.org/web/20171204222824/https://query.nytimes.com/gst/fullpage.html?sec=health&res=9F02E2DB153FF93AA25752C0A9609C8B63&n=Top%2fReference%2fTimes%20Topics%2fSubjects%2fO%2fOlympic%20Games | url-status=live }}</ref> It was removed from the list effective 1 January 2009, after improvements in testing methods made the ban unnecessary.<ref name="Australian">{{cite web | author = Staff | work = The Australian | date = 28 October 2008 | url = http://www.theaustralian.com.au/archive/news/wada-removes-finasteride-from-ban-list/story-e6frg7mo-1111117876628?nk=0afe1009eb17d32f8f4d47ff9e091a08 | title = WADA removes Finasteride from ban list }}</ref> Athletes who used finasteride and were banned from international competition include [[Skeleton (sport)|skeleton racer]] [[Zach Lund]], [[Bobsleigh|bobsledder]] [[Sebastien Gattuso]], [[Football (soccer)|footballer]] [[Romário]], and [[Goaltender|ice hockey goaltender]] [[José Théodore]].<ref name=Australian/><ref>{{cite web | author = Staff | work = Sydney Morning Herald | date = 9 October 2008 | url = http://www.smh.com.au/zoom/archive/d229652 | title = WADA takes Romario's drug off banned list | access-date = 25 October 2014 | archive-date = 25 September 2015 | archive-url = https://web.archive.org/web/20150925030419/http://www.smh.com.au/zoom/archive/d229652 | url-status = dead }}</ref> |
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===Miscellaneous=== |
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The U.S. [[Food and Drug Administration]] advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride.<ref>{{cite web | url = https://www.fda.gov/downloads/BiologicsBloodVaccines/.../UCM062813.pdf | title = Deferral of Blood and Plasma donors – Medications | publisher = [[FDA]] | date = 28 July 1993 | access-date = 4 February 2017 | archive-date = 8 February 2017 | archive-url = https://web.archive.org/web/20170208141513/http://www.fda.gov/downloads/BiologicsBloodVaccines/.../UCM062813.pdf | url-status = live }}</ref> The UK also has a one-month deferral period.<ref>{{Cite web|title=Anti-Androgens - Joint United Kingdom Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee|url=https://www.transfusionguidelines.org/dsg/wb/guidelines/an027-anti-androgens|date=1 June 2007|website=www.transfusionguidelines.org|access-date=13 May 2020|archive-date=12 November 2020|archive-url=https://web.archive.org/web/20201112020418/https://www.transfusionguidelines.org/dsg/wb/guidelines/an027-anti-androgens|url-status=live}}</ref> |
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{{Reflist|35em}} |
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== |
==Research== |
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Preliminary research suggests that [[topical medication|topical]] finasteride may be effective in the treatment of [[pattern hair loss]].<ref name="pmid29601622">{{cite journal | vauthors = Lee SW, Juhasz M, Mobasher P, Ekelem C, Mesinkovska NA | title = A Systematic Review of Topical Finasteride in the Treatment of Androgenetic Alopecia in Men and Women | journal = Journal of Drugs in Dermatology | volume = 17 | issue = 4 | pages = 457–463 | date = April 2018 | pmid = 29601622 | pmc = 6609098 }}</ref><ref name="pmid31832993">{{cite journal | vauthors = Marks DH, Prasad S, De Souza B, Burns LJ, Senna MM | title = Topical Antiandrogen Therapies for Androgenetic Alopecia and Acne Vulgaris | journal = American Journal of Clinical Dermatology | volume = 21 | issue = 2 | pages = 245–254 | date = April 2020 | pmid = 31832993 | doi = 10.1007/s40257-019-00493-z | s2cid = 209331373 }}</ref> Topical finasteride, like the oral preparation, reduces serum DHT.<ref name="pmid31832993" /><ref name="pmid29601622"/> |
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* [http://www.proscar.com/ Proscar | Official website] |
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* [http://www.propecia.com Propecia | Official website] |
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DHT may be involved in the cause of [[acne]], and 5α-reductase inhibitors might be effective in the treatment of the condition.<ref name="Danby2015">{{cite book|vauthors=Danby FW|title=Acne: Causes and Practical Management|url=https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA147|date=27 January 2015|publisher=John Wiley & Sons|isbn=978-1-118-23277-4|pages=147–|access-date=24 March 2019|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031704/https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA147|url-status=live}}</ref><ref name="pmid23431485">{{cite journal | vauthors = Marchetti PM, Barth JH | title = Clinical biochemistry of dihydrotestosterone | journal = Ann. Clin. Biochem. | volume = 50 | issue = Pt 2 | pages = 95–107 | date = March 2013 | pmid = 23431485 | doi = 10.1258/acb.2012.012159 | s2cid = 8325257 | doi-access = free }}</ref> A small [[retrospective study]] reported that finasteride was effective in the treatment of acne in women with normal [[testosterone]] levels.<ref name="pmid30604525">{{cite journal | vauthors = Hu AC, Chapman LW, Mesinkovska NA | title = The efficacy and use of finasteride in women: a systematic review | journal = Int. J. Dermatol. | volume = 58| issue = 7| pages = 759–776| date = January 2019 | pmid = 30604525 | doi = 10.1111/ijd.14370 | s2cid = 58555908 }}</ref><ref name="pmid23431485" /> A [[randomized controlled trial]] found that finasteride was less effective than [[flutamide]] or an [[ethinylestradiol/cyproterone acetate]] [[birth control pill]] in the treatment of acne in women with [[hyperandrogenism|high androgen levels]].<ref name="pmid30604525" /> |
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{{Merck&Co}} |
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Androgens and [[estrogen]]s may be involved in the cause of [[hidradenitis suppurativa]] (acne inversa).<ref name="pmid19293006">{{cite journal | vauthors = Alikhan A, Lynch PJ, Eisen DB | title = Hidradenitis suppurativa: a comprehensive review | journal = J. Am. Acad. Dermatol. | volume = 60 | issue = 4 | pages = 539–61; quiz 562–3 | date = April 2009 | pmid = 19293006 | doi = 10.1016/j.jaad.2008.11.911 }}</ref><ref name="pmid28128074">{{cite journal | vauthors = Riis PT, Ring HC, Themstrup L, Jemec GB | title = The Role of Androgens and Estrogens in Hidradenitis Suppurativa - A Systematic Review | journal = Acta Dermatovenerol Croat | volume = 24 | issue = 4 | pages = 239–249 | date = December 2016 | pmid = 28128074 }}</ref> Two [[case series]] have reported that finasteride is effective in the treatment of hidradenitis suppurativa in girls and women.<ref name="pmid30604525" /> |
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Finasteride and other antiandrogens might be useful in the treatment of [[obsessive–compulsive disorder]], but more research is needed.<ref name="pmid31814547">{{cite journal | vauthors = Nomani H, Mohammadpour AH, Moallem SM, YazdanAbad MJ, Barreto GE, Sahebkar A | title = Anti-androgen drugs in the treatment of obsessive-compulsive disorder: a systematic review | journal = Curr Med Chem | date = December 2019 | volume = 27 | issue = 40 | pages = 6825–6836 | pmid = 31814547 | doi = 10.2174/0929867326666191209142209| s2cid = 208956450 }}</ref> |
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==References== |
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{{Reflist}} |
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{{Androgens and antiandrogens}} |
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{{Drugs used in benign prostatic hypertrophy}} |
{{Drugs used in benign prostatic hypertrophy}} |
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{{Other dermatological preparations}} |
{{Other dermatological preparations}} |
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[[Category: |
[[Category:Wikipedia medicine articles ready to translate]] |
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[[Category:5α-Reductase inhibitors]] |
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[[Category:Androstanes]] |
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[[Category:Drugs developed by Merck & Co.]] |
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[[Category:Carboxamides]] |
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[[Category:Hair loss medications]] |
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[[Category:Hair removal]] |
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[[Category:Delta-lactams]] |
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[[Category:Teratogens]] |
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[[Category:Tert-butyl compounds]] |
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[[Category:Heterocyclic compounds with 4 rings]] |
Revision as of 17:44, 10 April 2024
Clinical data | |
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Trade names | Proscar, Propecia, Finide, others |
Other names | MK-906; YM-152; L-652,931; 17β-(N-tert-Butylcarbamoyl)-4-aza-5α-androst-1-en-3-one; N-(1,1-Dimethylethyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide |
AHFS/Drugs.com | Monograph |
MedlinePlus | a698016 |
License data |
|
Pregnancy category |
|
Routes of administration | By mouth |
Drug class | 5α-Reductase inhibitor |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 65%[5] |
Protein binding | 90%[5] |
Metabolism | Liver (CYP3A4, ALDH)[5] |
Elimination half-life | Adults: 5–6 hours[5] Elderly: >8 hours[5] |
Excretion | Feces: 57%[5] Urine: 40%[5] |
Identifiers | |
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CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.149.445 |
Chemical and physical data | |
Formula | C23H36N2O2 |
Molar mass | 372.553 g·mol−1 |
3D model (JSmol) | |
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(verify) |
Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men.[6] It can also be used to treat excessive hair growth in women.[7][8] It is usually taken orally but there are topical formulations for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles.[9]
Finasteride is a 5α-reductase inhibitor and therefore an antiandrogen.[10] It works by decreasing the production of dihydrotestosterone (DHT) by about 70%.[6]
In addition to DHT, finasteride also inhibits the production of several anticonvulsant neurosteroids including allopregnanolone, androstanediol, and THDOC.[11]
Adverse effects from finasteride are rare;[12] however, some men experience sexual dysfunction, depression, and breast enlargement.[13][14] In some men, sexual dysfunction may persist after stopping the medication.[15][16] It may also hide the early symptoms of certain forms of prostate cancer.[14]
Finasteride was patented in 1984 and approved for medical use in 1992.[17] It is available as a generic medication.[18] In 2021, it was the 88th most commonly prescribed medication in the United States, with more than 8 million prescriptions.[19][20]
Medical uses
Finasteride has been used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate[3] and for the treatment of male pattern hair loss (androgenetic alopecia) in men.[4]
Enlarged prostate
Physicians sometimes prescribe finasteride for the treatment of benign prostatic hyperplasia (BPH), informally known as an enlarged prostate.[21] Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up during the night to urinate, hesitation at the start and end of urination, and decreased urinary flow.[22]
The use of the drug showed significant sexual adverse effects such as erectile dysfunction and less sexual desire, in particular when obstructive symptoms due to an enlarged prostate were present.[23]
Scalp hair loss
Finasteride is also used to treat male pattern baldness (androgenic alopecia) in men, a condition that develops in up to 80% of Caucasian men aged 70 and over.[24][4] In the United States, finasteride and minoxidil are the only two FDA approved drugs for the treatment of male pattern hair loss as of 2017.[25] Treatment with finasteride slows further hair loss[26] and provides about 30% improvement in hair loss after six months of treatment, with effectiveness persisting as long as the drug is taken.[14] Taking finasteride leads to a reduction in scalp and serum DHT levels; by lowering scalp levels of DHT, finasteride can maintain or increase the amount of terminal hairs in the anagen phase by inhibiting and sometimes reversing miniaturization of the hair follicle. Finasteride is most effective on the crown but can reduce hair loss in all areas of the scalp.[27][28] Finasteride has also been tested for pattern hair loss in women; however, the results were no better than placebo.[29] Finasteride is less effective in the treatment of scalp hair loss than dutasteride.[30][31]
Prostate cancer
In males aged 55 years old and over finasteride decreases the risk of low-grade prostate cancer but may increase the risk of high-grade prostate cancer and has no effect on overall survival.[32]
A 2010 review found a 25% reduction in the risk of prostate cancer with 5α-reductase inhibitor.[33] A follow-up study of the Medicare claims of participants in a 10-year Prostate Cancer Prevention Trial suggests the reduction in prostate cancer is maintained even after discontinuation of treatment.[34] However, 5α-reductase inhibitors have been found to increase the risk of developing certain rare but aggressive forms of prostate cancer (27% risk increase), although not all studies have observed this.[35] No impact of 5-α-reductase inhibitor on survival has been found in people with prostate cancer.[35]
Excessive hair growth
Finasteride has been found to be effective in the treatment of hirsutism (excessive facial and/or body hair growth) in women. In a study of 89 women with hyperandrogenism due to persistent adrenarche syndrome, finasteride produced a 93% reduction in facial hirsutism and a 73% reduction bodily hirsutism after 2 years of treatment. Other studies using finasteride for hirsutism have also found it to be clearly effective.[7]
Transgender hormone therapy
Finasteride is sometimes used in hormone replacement therapy for transgender women due to its antiandrogenic effects, in combination with a form of estrogen. However, little clinical research of finasteride use for this purpose has been conducted and evidence of safety or efficacy is limited.[8] Moreover, caution has been recommended when prescribing finasteride to transgender women, as finasteride may be associated with side effects such as depression, anxiety, and suicidal ideation, symptoms that are particularly prevalent in the transgender population and in others at high risk already.[36]
Adverse effects
A 2010 Cochrane review of finasteride for BPH found that, in men with a weighted mean age of 62.4, adverse effects are "rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo."[12] As of 2016 fresh evidence suggested such effects, along with disturbed neurosteroid production, may persist after finasteride use is stopped.[37]
Finasteride is contraindicated in pregnancy.[38][39] The Food and Drug Administration advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride.[40]
The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer, as the treatment of BPH lowers PSA (prostate-specific antigen), which could mask the development of prostate cancer.[41][42] Although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not increased, there are post-marketing reports of breast cancer in association with its use, though available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers.[4][43] A 2018 meta-analysis found no higher risk of breast cancer with 5α-reductase inhibitors.[44] Some men develop gynecomastia (breast development or enlargement) following finasteride usage.[45][46][47][48] The risk of gynecomastia with 5α-reductase inhibitors is low at about 1.5%.[49] Depressive symptoms and suicidality have been reported.[50]
Sexual adverse effects
Use of finasteride is associated with an increased risk of sexual dysfunction including erectile dysfunction, decreased libido and ejaculatory dysfunction.[51][13] Sexual adverse effects of finasteride and dutasteride have been linked to lower quality of life and ability to maintain an intimate relationship, and can cause stress in relationships.[52]
The adverse effect profiles of finasteride are somewhat different for its indications of hair loss and BPH.
Finasteride for androgenetic alopecia (hair loss in men)
The most common adverse effects of finasteride taken for hair loss are: decrease in sex drive, erectile dysfunction and decrease in amount of semen.[38]: 17
In addition, finasteride has been reported in case reports to cause sexual problems which persist after stopping the medication.[16][15] A 2012 update to the FDA label noted reports of decreased sex drive, problems with ejaculation and difficulty achieving an erection which continued after stopping the medication. The update also referenced reports of testicular pain and "male infertility and/or poor quality of semen."[38]: 17 [14][53][49]
Finasteride for BPH
The most common adverse sexual effects of finasteride for BPH are: trouble getting or keeping an erection, decrease in sex drive, decreased volume of ejaculate and ejaculation disorders.[39]: 16
A 2010 Cochrane review found that men taking finasteride for BPH (with a mean age of 62.4) are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder for the first year of treatment. The rates became indistinguishable from placebo after 2–4 years and these side effects usually got better over time.[12]
Long-term
Finasteride may cause persistent adverse sexual, neurological and physical effects in a subset of men.[15] A 2019 metastudy surveyed the literature on the reversibility of finasteride's side effects. It identified three studies which demonstrated full reversibility of side effects and eleven that describe patients with irreversible adverse events. The findings were most convincing in a retrospective review of about 12,000 patients that 1.4% of the cohort developed persistent ED[15] (ED lasting longer than 90 days post-withdrawal).[54]
Post-finasteride syndrome
Reports of long-term, post-discontinuation adverse effects in some fraction of former finasteride users have led to a proposed post-finasteride syndrome, although some within the medical community question whether there is enough evidence to support a causal relationship between finasteride usage and PFS.[55]
Individuals claiming to experience PFS report sexual, neurological, hormonal and psychological side effects that persist for an extended period after stopping the drug.[56] Reported symptoms include penile atrophy and tissue changes, decreased ejaculate volume and quality, reduced libido, erectile dysfunction, loss of penile sensitivity, decreased orgasm sensation, dry skin, metabolic changes, muscle and strength loss, gynecomastia, depression, anxiety, panic attacks, insomnia, anhedonia, concentration problems, memory impairment and suicidal ideation.[57] A meta-analysis found significant association between finasteride use and post-discontinuation depression, suicidal ideation, and sexual dysfunction, but the quality of evidence was limited.[58]
The status of PFS as a legitimate and distinct medical pathology remains a subject of debate. A 2019 editorial in The BMJ called post-finasteride syndrome "ill defined and controversial".[59] Some have argued that it has common features with other self-diagnosed "mystery syndromes" such as Morgellons or multiple chemical sensitivity, while others, including some in the biomedical research community, have concluded based on the available evidence that it represents a real and serious condition.[16] There is no known underlying biological mechanism for the proposed syndrome, and its incidence is unclear.[60] A lack of clear diagnostic criteria and the variable reporting fraction in different health-care settings make the problem challenging to evaluate.[57]
As of 2016, Merck was a defendant in approximately 1,370 product liability lawsuits which had been filed by customers alleging they have experienced persistent sexual side effects following cessation of treatment with finasteride.[61] Most cases were settled by 2018 when Merck paid a lump sum of $4.3 million USD to be distributed. As of September 2019, 25 cases remained outstanding in the United States.[62] In 2019, Reuters reported that faulty redactions in court documents revealed allegations from plaintiffs that Merck had known of persistent side effects in their original clinical trials but chose not to disclose them in warning labels.[62]
Overdose
Finasteride has been studied in humans at single doses of up to 400 mg and at continuous dosages of up to 80 mg/day for three months, without adverse effects observed.[4][3][63] There is no specific recommended antidote for finasteride overdose.[4][3]
Interactions
No significant drug interactions have been observed between finasteride and a limited selection of medications.[64]
Pharmacology
Pharmacodynamics
Finasteride is a 5α-reductase inhibitor.[4][5] It is specifically a selective inhibitor of the type II and III isoforms of the enzyme.[5][65][66] By inhibiting these two isozymes of 5α-reductase, finasteride reduces the formation of the potent androgen dihydrotestosterone (DHT) from its precursor testosterone in certain tissues in the body such as the prostate gland, skin, and hair follicles.[5][67] As such, finasteride is a type of antiandrogen, or more specifically, an androgen synthesis inhibitor.[68][69] However, some authors do not define finasteride as an "antiandrogen," a term which can refer more specifically to antagonists of the androgen receptor.[70]
Finasteride results in a decrease of circulating DHT levels by about 65–70% with an oral dosage of 5 mg/day and of DHT levels in the prostate gland by up to 80–90% with an oral dosage of 1 or 5 mg/day.[65][71][72] In parallel, circulating levels of testosterone increase by approximately 10%, while local concentrations of testosterone in the prostate gland increase by about 7-fold and local testosterone levels in hair follicles increase by around 27–53%.[73][74] An oral dosage of finasteride of only 0.2 mg/day has been found to achieve near-maximal suppression of DHT levels (68.6% for 0.2 mg/day relative to 72.2% for 5 mg/day).[74][75] Finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the 5α-reductase type I isoenzyme, with more than 100-fold less inhibitory potency for type I as compared to type II (IC50 = 313 nM and 11 nM, respectively).[4][5] This is in contrast to inhibitors of all three isoenzymes of 5α-reductase like dutasteride, which can reduce DHT levels in the entire body by more than 99%.[65] In addition to inhibiting 5α-reductase, finasteride has also been found to competitively inhibit 5β-reductase (AKR1D1).[76] However, its affinity for the enzyme is substantially less than for 5α-reductase (an order of magnitude less than for 5α-reductase type I) and hence is unlikely to be of clinical significance.[76]
As of 2012, the tissues in which the different isozymes of 5α-reductase are expressed are not fully clear.[67] This is because different investigators have obtained varying results with different reagents, methods, and tissues examined.[67] However, the different isozymes of 5α-reductase appear to be widely expressed, with notable tissues including the prostate gland, seminal vesicles, testes, epididymides, skin, hair follicles, liver, kidneys, and brain, among others.[67]
By inhibiting 5α-reductase and thus preventing DHT production, finasteride reduces androgen signaling in tissues like the prostate gland and the scalp. In the prostate, this reduces prostate volume, which improves BPH and reduces risk of prostate cancer. Finasteride reduces prostate volume by 20 to 30% in men with benign prostatic hyperplasia.[77] Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.[78]
Neurosteroids like 3α-androstanediol (derived from DHT) and allopregnanolone (derived from progesterone) activate the GABAA receptor in the brain; because finasteride prevents the formation of neurosteroids, it functions as a neurosteroidogenesis inhibitor and may contribute to a reduction of GABAA activity. Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression, anxiety, and sexual dysfunction.[79][80][81]
In accordance with finasteride being a potent 5α-reductase inhibitor but a weak inhibitor of 5β-reductase, the medication decreases circulating levels of 5α-reduced steroids like allopregnanolone but does not reduce concentrations of 5β-reduced steroids like pregnanolone.[82][83][84] Pregnanolone acts as a potent GABAA receptor positive allosteric modulator similarly to allopregnanolone.[85]
Pharmacokinetics
The mean oral bioavailability of finasteride is approximately 65%.[5] The absorption of finasteride is not affected by food.[4][3] At steady-state with 1 mg/day finasteride, mean peak concentrations of finasteride were 9.2 ng/mL (25 nmol/L).[4] Conversely, following a single 5 mg dose of finasteride, mean peak levels of finasteride were 37 ng/mL (99 nmol/L), and plasma concentrations increased by 47–54% following 2.5 weeks of continued daily administration.[3] The volume of distribution of finasteride is 76 L.[5] Its plasma protein binding is 90%.[5] The drug has been found to cross the blood–brain barrier, whereas levels in semen were found to be undetectable.[5]
Finasteride is extensively metabolized in the liver, first by hydroxylation via CYP3A4 and then by aldehyde dehydrogenase.[5] It has two major metabolites, which are the tert-butyl side chain monohydroxylated and monocarboxylic acid metabolites.[5] These metabolites show approximately 20% of the inhibitory activity of finasteride on 5α-reductase.[5] Hence, the metabolites of finasteride are not particularly active.[5] The drug has a terminal half-life of 5 to 6 hours in adult men (18–60 years of age) and a terminal half-life of 8 hours or more in elderly men (more than 70 years of age).[5] It is eliminated as its metabolites 57% in the feces and 40% in the urine.[5]
Chemistry
Finasteride, also known as 17β-(N-tert-butylcarbamoyl)-4-aza-5α-androst-1-en-3-one, is a synthetic androstane steroid and 4-azasteroid.[64][86] It is an analogue of androgen steroid hormones like testosterone and DHT.[64] As an unconjugated steroid, finasteride is a highly lipophilic compound.[64][87]
History
In 1942, James Hamilton observed that prepubertal castration prevents the later development of male pattern baldness in mature men.[88] In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on birth defects. She reported on a group of intersex children in the Caribbean who appeared sexually ambiguous at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic after onset of puberty. These children, despite being raised as girls until puberty, were generally heterosexual, and were termed "Guevedoces" by their local community, which means "penis at twelve" in Spanish.[89] Her research group found these children shared a genetic mutation, causing deficiency of the 5α-reductase enzyme and male hormone dihydrotestosterone (DHT), which was found to have been the etiology behind abnormalities in male sexual development. Upon maturation, these individuals were observed to have smaller prostates which were underdeveloped, and were also observed to lack incidence of male pattern baldness.[90][91]
In 1975, copies of Imperato-McGinley's presentation were seen by P. Roy Vagelos, who was then serving as Merck's basic-research chief. He was intrigued by the notion that decreased levels of DHT led to the development of smaller prostates. Dr. Vagelos then sought to create a drug which could mimic the condition found in these children to treat older men who had benign prostatic hyperplasia.[92]
Finasteride was developed by Merck under the code name MK-906.[64] A team led by chemist Gary Rasmusson and biologist Jerry Brooks developed potential 5α-reductase inhibitors based on transition state inhibitors, using an iterative process of molecular design, testing, and redesign.[93] In 1992, finasteride (5 mg) was approved by the U.S. Food and Drug Administration (FDA) for treatment of BPH, which Merck marketed under the brand name Proscar. Rasmusson and Brooks were awarded IPO's "Inventor of the Year" award in 1993 for their work on finasteride.[94] In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg) for treatment of male pattern hair loss, which was marketed under the brand name Propecia.[95] It was the first 5α-reductase inhibitor to be introduced and was followed by dutasteride in 2001.[96] The first study of finasteride in the treatment of hirsutism in women was published in 1994.[97]
Society and culture
Generic names
Finasteride is the generic name of the drug and its INN , USAN , BAN , and JAN , while finastéride is its DCF .[98][99][100][101] It is also known by its former developmental code names MK-906, YM-152, and L-652,931.[98][99][100][101]
Brand names
Finasteride is marketed primarily under the brand names Propecia, for pattern hair loss, and Proscar, for BPH, both of which are products of Merck & Co.[101] There is 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck's patent on finasteride for the treatment of BPH expired in June 2006.[102] Merck was awarded a separate patent for the use of finasteride to treat pattern hair loss and it expired in November 2013.[103] Finasteride is also marketed under a variety of other brand names throughout the world.[101]
Athletics
From 2005 to 2009, the World Anti-Doping Agency banned finasteride because it was discovered that the drug could be used to mask steroid abuse.[104] It was removed from the list effective 1 January 2009, after improvements in testing methods made the ban unnecessary.[105] Athletes who used finasteride and were banned from international competition include skeleton racer Zach Lund, bobsledder Sebastien Gattuso, footballer Romário, and ice hockey goaltender José Théodore.[105][106]
Miscellaneous
The U.S. Food and Drug Administration advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride.[107] The UK also has a one-month deferral period.[108]
Research
Preliminary research suggests that topical finasteride may be effective in the treatment of pattern hair loss.[109][110] Topical finasteride, like the oral preparation, reduces serum DHT.[110][109]
DHT may be involved in the cause of acne, and 5α-reductase inhibitors might be effective in the treatment of the condition.[111][112] A small retrospective study reported that finasteride was effective in the treatment of acne in women with normal testosterone levels.[113][112] A randomized controlled trial found that finasteride was less effective than flutamide or an ethinylestradiol/cyproterone acetate birth control pill in the treatment of acne in women with high androgen levels.[113]
Androgens and estrogens may be involved in the cause of hidradenitis suppurativa (acne inversa).[114][115] Two case series have reported that finasteride is effective in the treatment of hidradenitis suppurativa in girls and women.[113]
Finasteride and other antiandrogens might be useful in the treatment of obsessive–compulsive disorder, but more research is needed.[116]
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