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Review the information below for assistance if you do not believe that you have done anything wrong.<div class="paragraphbreak" style="margin-top:0.5em"></div><div class="paragraphbreak" style="margin-top:0.5em"></div> <p>This block affects editing on all Wikimedia wikis. </p><p>The IP address or range 8.222.128.0/17 has been globally <a href="/wiki/Wikipedia:Blocking_policy" title="Wikipedia:Blocking policy">blocked</a> by <a href="/wiki/User:Jon_Kolbert" title="User:Jon Kolbert">‪Jon Kolbert‬</a> for the following reason(s): </p> <div style="padding:10px; background:var(--background-color-base, white); color:inherit; border:1px #666 solid;"> <p><a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/NOP" class="extiw" title="m:Special:MyLanguage/NOP">Open proxy/Webhost</a>: See the <a href="https://meta.wikimedia.org/wiki/WM:OP/H" class="extiw" title="m:WM:OP/H">help page</a> if you are affected </p> </div> <p>This block will expire on 15:12, 27 August 2028. Your current IP address is 8.222.208.146. </p> <div class="paragraphbreak" style="margin-top:0.5em"></div><div style="font-size: 16px;"> <p>Even while globally blocked, you will <i>usually</i> still be able to edit pages on <a href="https://meta.wikimedia.org/wiki/" class="extiw" title="m:">Meta-Wiki</a>. </p> </div> <div class="paragraphbreak" style="margin-top:0.5em"></div><div style="font-size: 16px;"> <p>If you believe you were blocked by mistake, you can find additional information and instructions in the <a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/No_open_proxies" class="extiw" title="m:Special:MyLanguage/No open proxies">No open proxies</a> global policy. Otherwise, to discuss the block please <a href="https://meta.wikimedia.org/wiki/Steward_requests/Global" class="extiw" title="m:Steward requests/Global">post a request for review on Meta-Wiki</a>. You could also send an email to the <a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/Stewards" class="extiw" title="m:Special:MyLanguage/Stewards">stewards</a> <a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/VRT" class="extiw" title="m:Special:MyLanguage/VRT">VRT</a> queue at <kbd>stewards@wikimedia.org</kbd> including all above details. </p> </div> <p>Other useful links: <a href="https://meta.wikimedia.org/wiki/Global_blocks" class="extiw" title="m:Global blocks">Global blocks</a> · <a href="/wiki/Help:I_have_been_blocked" title="Help:I have been blocked">Help:I have been blocked</a> </p> </div></li></ul><hr /> <div id="viewsourcetext">You can view and copy the source of this page:</div><textarea readonly="" accesskey="," id="wpTextbox1" cols="80" rows="25" style="" class="mw-editfont-monospace" lang="en" dir="ltr" name="wpTextbox1">{{Short description|Class of medications}} {{Infobox drug class | Image = Dutasteride.svg | ImageClass = skin-invert-image | Alt = | Caption = [[Dutasteride]], one of the most widely used 5α-reductase inhibitors. | Width = 250px | Synonyms = Dihydrotestosterone blockers; DHT blockers  | Use = [[Benign prostatic hyperplasia]], [[pattern hair loss]], [[hirsutism]], [[Feminizing hormone therapy|feminizing HRT]] | ATC_prefix = G04CB | Biological_target = [[5α-Reductase]] ([[SRD5A1|1]], [[SRD5A2|2]], [[SRD5A3|3]]) | Chemical_class = [[Steroid]]s; [[Azasteroid]]s  | Drugs.com = | Consumer_Reports = | medicinenet = | rxlist =  | MeshID = }} '''5α-Reductase inhibitors''' ('''5-ARIs'''), also known as '''dihydrotestosterone''' ('''DHT''') '''blockers''', are a class of [[medication]]s with [[antiandrogen]]ic effects which are used primarily in the treatment of [[benign prostatic hyperplasia|enlarged prostate]] and [[pattern hair loss|scalp hair loss]]. They are also sometimes used to treat [[hirsutism|excess hair growth]] in women and as a component of [[feminizing hormone therapy|hormone therapy]] for [[transgender women]].<ref name="Blume-PeytaviWhiting2008">{{cite book|author1=Ulrike Blume-Peytavi|author2=David A. Whiting|author3=Ralph M. Trüeb|title=Hair Growth and Disorders|url=https://books.google.com/books?id=pHrX2-huQCoC&pg=PA368|date=26 June 2008|publisher=Springer Science & Business Media|isbn=978-3-540-46911-7|pages=368–370|access-date=29 October 2016|archive-date=9 November 2023|archive-url=https://web.archive.org/web/20231109232624/https://books.google.com/books?id=pHrX2-huQCoC&pg=PA368#v=onepage&q&f=false|url-status=live}}</ref><ref name="pmid28159148">{{cite journal | vauthors = Wesp LM, Deutsch MB | title = Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons | journal = Psychiatr. Clin. North Am. | volume = 40 | issue = 1 | pages = 99–111 | year = 2017 | pmid = 28159148 | doi = 10.1016/j.psc.2016.10.006 }}</ref> These agents inhibit the [[enzyme]] [[5α-reductase]], which is involved in the [[metabolic transformation]]s of a variety of [[endogenous]] [[steroid]]s. 5-ARIs are most known for preventing conversion of [[testosterone]], the major [[androgen]] [[sex hormone]], to the more potent androgen [[dihydrotestosterone]] (DHT), in certain [[androgen-associated disorder]]s. {{TOC limit|3}} ==Medical uses== 5-ARIs are clinically used in the treatment of conditions that are exacerbated by DHT:<ref name="Rossi">Rossi S (Ed.) (2004). ''[[Australian Medicines Handbook]] 2004''. Adelaide: Australian Medicines Handbook. {{ISBN|0-9578521-4-2}}</ref> * Mild-to-moderate [[benign prostatic hyperplasia]] and [[lower urinary tract symptoms]] * [[Pattern hair loss]] in both men and women 5-ARIs can be used in the treatment of [[hirsutism]] in women.<ref name="Blume-PeytaviWhiting2008" /> The usefulness of 5-ARIs for the potential treatment of [[acne]] is uncertain.<ref name="pmid22235201" /> 5-ARIs are sometimes used as antiandrogens in [[feminizing hormone therapy]] for [[transgender women]] to help reduce body hair growth and scalp hair loss.<ref name="pmid28159148" /> They have also been explored in the treatment and prevention of [[prostate cancer]]. While the 5-ARI [[finasteride]] reduces the cancer risk by about a third, it also increases the fraction of aggressive forms of prostate cancer. Overall, there does not seem to be a survival benefit for prostate cancer patients under finasteride.<ref>{{Cite journal|last1=Thompson|first1=Ian M. Jr.|last2=Goodman|first2=Phyllis J.|last3=Tangen|first3=Catherine M.|last4=Parnes|first4=Howard L.|last5=Minasian|first5=Lori M.|last6=Godley|first6=Paul A.|last7=Lucia|first7=M. Scott|last8=Ford|first8=Leslie G.|date=2013-08-15|title=Long-Term Survival of Participants in the Prostate Cancer Prevention Trial|journal=New England Journal of Medicine|volume=369|issue=7|pages=603–610|doi=10.1056/NEJMoa1215932|issn=0028-4793| pmc=4141537 |pmid=23944298}}</ref> ===Available forms=== [[Finasteride]] (brand names Proscar, Propecia) inhibits the function of two of the isoenzymes (types 2 and 3) of 5α-reductase.<ref name="Yamana_2010">{{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 |date=January 2010 | volume = 2 | issue = 3 | pages = 293–9 | doi = 10.1515/hmbci.2010.035 | pmid = 25961201 | s2cid = 28841145 }}</ref><ref>{{cite journal |author1=Yamana K. |author2=Labrie F. |author3=Luu-The V. | year = 2010 | 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 finasteride and dutasteride | journal = Hormone Molecular Biology and Clinical Investigation | volume = 2 | issue = 3| pages = 293–299 | doi=10.1515/hmbci.2010.035|pmid=25961201 |s2cid=28841145 |display-authors=etal}}</ref> It decreases circulating DHT levels by up to about 70%.<ref>{{cite journal |author1=McConnell J. D. |author2=Wilson J. D. |author3=George F. W. |author4=Geller J. |author5=Pappas F. |author6=Stoner E. | year = 1992 | title = Finasteride, an inhibitor of 5α-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia | journal = Journal of Clinical Endocrinology and Metabolism | volume = 74 | issue = 3| pages = 505–508 |doi=10.1210/jcem.74.3.1371291 | pmid=1371291}}</ref> [[Dutasteride]] (brand name Avodart) inhibits all three 5α-reductase isoenzymes and can decrease DHT levels by 95%.<ref>{{cite journal |author1=Clark R. V. |author2=Hermann D. J. |author3=Cunningham G. R. |author4=Wilson T. H. |author5=Morrill B. B. |author6=Hobbs S. | year = 2004 | title = Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5α-reductase inhibitor | journal = Journal of Clinical Endocrinology and Metabolism | volume = 89 | issue = 5| pages = 2179–2184 | doi=10.1210/jc.2003-030330 | pmid=15126539}}</ref><ref>{{cite journal | author = Moss G. P. | year = 1989 | title = Nomenclature of steroids (Recommendations 1989) | journal = Pure and Applied Chemistry | volume = 61 | issue = 10| pages = 1783–1822 | doi=10.1351/pac198961101783| s2cid = 97612891 | doi-access = free }}</ref> It can also reduce DHT levels in the prostate by 97 to 99% in men with prostate cancer.<ref>G. L. Andriole, P. Humphrey, P. Ray et al., "Effect of the dual 5α-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer,"</ref><ref>{{cite journal |author1=Gleave M. |author2=Qian J. |author3=Andreou C. | year = 2006 | title = The effects of the dual 5α-reductase inhibitor dutasteride on localized prostate cancer—results from a 4-month pre-radical prostatectomy study | journal = The Prostate | volume = 66 | issue = 15| pages = 1674–1685 | doi=10.1002/pros.20499|display-authors=etal | pmid=16927304|s2cid=40446842 | doi-access=free }}</ref> [[Epristeride]] (brand names Aipuliete, Chuanliu) is marketed in [[China]] for the treatment of benign prostatic hyperplasia.<ref name="MortonHall1999-Epristeride">{{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA113|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=113–|access-date=4 June 2017|archive-date=24 February 2024|archive-url=https://web.archive.org/web/20240224185652/https://books.google.com/books?id=mqaOMOtk61IC&pg=PA113#v=onepage&q&f=false|url-status=live}}</ref><ref name="AdisInsight-Epristeride">{{Cite web|url=http://adisinsight.springer.com/drugs/800002533|title=Epristeride - AdisInsight|access-date=2017-06-04|archive-date=2016-11-08|archive-url=https://web.archive.org/web/20161108135117/http://adisinsight.springer.com/drugs/800002533|url-status=live}}</ref><ref name="Drugs.com-Epristeride">{{Cite web|url=https://www.drugs.com/international/epristeride.html|title=List of 21 Benign Prostatic Hyperplasia Medications Compared|access-date=2017-06-04|archive-date=2017-12-11|archive-url=https://web.archive.org/web/20171211105106/https://www.drugs.com/international/epristeride.html|url-status=live}}</ref> However, it can only decrease circulating DHT levels by about 25 to 54%.<ref name="Publishers1996">{{cite book|author=Bentham Science Publishers|title=Current Pharmaceutical Design|url=https://books.google.com/books?id=IYn4Va7wtAoC&pg=PA70|date=February 1996|publisher=Bentham Science Publishers|pages=70–}}</ref> [[Alfatradiol]] (brand names Ell-Cranell Alpha, Pantostin) is a topical 5-ARI used to treat pattern hair loss in [[Europe]].<ref name="Hunnius">{{cite book|editor1-first=Artur|editor1-last=Berger|editor2-first=Helmut|editor2-last=Wachter|title=Hunnius Pharmazeutisches Wörterbuch|edition=8th|publisher=Walter de Gruyter Verlag|year=1998|language=de|page=486|isbn=978-3-11-015793-2}}</ref><ref name="Mutschler">{{cite book|last=Mutschler|first=Ernst|author2=Gerd Geisslinger|author3=Heyo K. Kroemer|author4=Monika Schäfer-Korting|title=Arzneimittelwirkungen|publisher=Wissenschaftliche Verlagsgesellschaft|location=Stuttgart|year=2001|edition=8th|page=453|isbn=978-3-8047-1763-3|language=de}}</ref> {{5α-Reductase inhibitors marketed for clinical or veterinary use}} ==Side effects== 5-ARIs are generally [[drug tolerability|well tolerated]] in both men and women and produce few [[side effect]]s.<ref name="pmid27672412">{{cite journal | vauthors = Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS | 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 | year = 2016 | pmid = 27672412 | pmc = 5023004 }}</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> However, they have been found to have some risks in studies with men, including slightly increased risks of decreased [[libido]], [[erectile dysfunction]], [[ejaculatory dysfunction (disambiguation)|ejaculatory dysfunction]], [[infertility]], [[breast tenderness]], [[gynecomastia]], [[depression (mood)|depression]], [[anxiety]], [[self-harm]], and [[dementia]].<ref name="pmid27784557" /><ref name="pmid28319231">{{cite journal | vauthors = Welk B, McArthur E, Ordon M, Anderson KK, Hayward J, Dixon S | title = Association of Suicidality and Depression With 5α-Reductase Inhibitors | journal = JAMA Intern Med | volume = 177 | issue = 5 | pages = 683–691 | year = 2017 | pmid = 28319231 | pmc = 5818776 | doi = 10.1001/jamainternmed.2017.0089 }}</ref><ref name="WelkMcArthur2017">{{cite journal|last1=Welk|first1=Blayne|last2=McArthur|first2=Eric|last3=Ordon|first3=Michael|last4=Morrow|first4=Sarah A.|last5=Hayward|first5=Jade|last6=Dixon|first6=Stephanie|title=The risk of dementia with the use of 5 alpha reductase inhibitors|journal=Journal of the Neurological Sciences|volume=379|year=2017|pages=109–111|issn=0022-510X|doi=10.1016/j.jns.2017.05.064|pmid=28716218|s2cid=4765640}}</ref> In addition, although 5-ARIs decrease the overall risk of developing [[prostate cancer]], they have been found to increase the risk of developing certain rare but high-grade forms of prostate cancer.<ref name="pmid27672412" /> As a result, the FDA has notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-ARI class of drugs has been revised to include new safety information about the increased risk of being diagnosed with these rare but more serious forms of prostate cancer.<ref name="Drugs.com-Label">{{cite web |url=https://www.drugs.com/fda/5-alpha-reductase-inhibitors-5-aris-label-change-increased-risk-prostate-cancer-12977.html |title=FDA Alert: 5-alpha reductase inhibitors (5-ARIs): Label Change – Increased Risk of Prostate Cancer |publisher=Drugs.com |access-date=2014-06-08 |archive-date=2014-07-14 |archive-url=https://web.archive.org/web/20140714153526/http://www.drugs.com/fda/5-alpha-reductase-inhibitors-5-aris-label-change-increased-risk-prostate-cancer-12977.html |url-status=live }}</ref> Finasteride has also been associated with [[intraoperative floppy iris syndrome]] and [[cataract]] formation.<ref name="pmid21555201">{{Cite journal | last1 = Wong | first1 = A. C. M. | last2 = Mak | first2 = S. T. | doi = 10.1016/j.jcrs.2011.04.013 | title = Finasteride-associated cataract and intraoperative floppy-iris syndrome | journal = Journal of Cataract & Refractive Surgery | volume = 37 | issue = 7 | pages = 1351–1354 | year = 2011 | pmid = 21555201 }}</ref><ref name="pmid18053919">{{Cite journal | last1 = Issa | first1 = S. A. | last2 = Dagres | first2 = E. | doi = 10.1016/j.jcrs.2007.07.025 | title = Intraoperative floppy-iris syndrome and finasteride intake | journal = Journal of Cataract & Refractive Surgery | volume = 33 | issue = 12 | pages = 2142–2143 | year = 2007 | pmid = 18053919 }}</ref> 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> ===Sexual dysfunction=== [[Sexual dysfunction]], including [[erectile dysfunction]], [[loss of libido]], and [[hypospermia|reduced ejaculate]], may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride.<ref name="pmid27672412" /><ref name="pmid27475241">{{cite journal|last1=Liu|first1=L|last2=Zhao|first2=S|last3=Li|first3=F|last4=Li|first4=E|last5=Kang|first5=R|last6=Luo|first6=L|last7=Luo|first7=J|last8=Wan|first8=S|last9=Zhao|first9=Z|title=Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.|journal=The Journal of Sexual Medicine|date=September 2016|volume=13|issue=9|pages=1297–310|doi=10.1016/j.jsxm.2016.07.006|pmid=27475241}}</ref> This is linked to lower [[quality of life]] and can cause stress in relationships.<ref name=Gur2013>{{cite journal|last=Gur|first=S|author2=Kadowitz, PJ |author3=Hellstrom, WJ |title=Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation.|journal=Expert Opinion on Drug Safety|date=January 2013|volume=12|issue=1|pages=81–90|pmid=23173718|doi=10.1517/14740338.2013.742885|s2cid=11624116}}</ref> There is also an association with lowered sexual desire.<ref name=Tra2011>{{cite journal|last=Traish|first=AM|author2=Hassani, J |author3=Guay, AT |author4=Zitzmann, M |author5= 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|date=March 2011|volume=8|issue=3|pages=872–84|pmid=21176115|doi=10.1111/j.1743-6109.2010.02157.x}}</ref> It has been reported that in a subset of men, these adverse sexual side effects may persist even after discontinuation of finasteride or dutasteride.<ref name=Tra2011/> ===Breast changes=== 5-ARIs have a small risk of [[breast]] changes in men including [[breast tenderness]] and [[gynecomastia]] (breast development/enlargement).<ref name="pmid27784557" /> The risk of gynecomastia is about 1.3%.<ref name="pmid27784557" /> There is no association of 5-ARIs with [[male breast cancer]].<ref name="pmid27784557" /><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> ===Emotional changes=== A 2017 [[population study|population-based]], [[matching (statistics)|matched]]-[[cohort study]] of 93,197 men aged 66&nbsp;years and older with BPH found that finasteride and dutasteride were associated with a significantly increased risk of depression ({{abbrlink|HR|Hazard ratio}}, 1.94; 95% {{abbrlink|CI|Confidence interval}}, 1.73–2.16) and [[self-harm]] (HR, 1.88; 95% CI, 1.34–2.64) during the first 18&nbsp;months of treatment, but were not associated with an increased risk of [[suicide]] (HR, 0.88; 95% CI, 0.53–1.45).<ref name="pmid29528971">{{cite journal | vauthors = Lee JY, Cho KS | title = Effects of 5-alpha reductase inhibitors: new insights on benefits and harms | journal = Curr Opin Urol | volume = 28 | issue = 3 | pages = 288–293 | date = May 2018 | pmid = 29528971 | doi = 10.1097/MOU.0000000000000497 | s2cid = 4587434 }}</ref><ref name="Traish2018">{{cite journal|last1=Traish|first1=Abdulmaged M.|title=The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption|journal=Current Sexual Health Reports|volume=10|issue=3|year=2018|pages=88–103|issn=1548-3584|doi=10.1007/s11930-018-0161-6|s2cid=81560714}}</ref><ref name="pmid30651009">{{cite journal | vauthors = Maksym RB, Kajdy A, Rabijewski M | title = Post-finasteride syndrome - does it really exist? | journal = Aging Male | volume = 22| issue = 4| pages = 250–259 | date = January 2019 | pmid = 30651009 | doi = 10.1080/13685538.2018.1548589 | s2cid = 58569946 | doi-access = free }}</ref><ref name="pmid28319231" /> After the initial 18&nbsp;months of therapy, the risk of self-harm was no longer heightened, whereas the elevation in risk of depression lessened but remained marginally increased (HR, 1.22; 95% CI, 1.08–1.37).<ref name="pmid29528971" /><ref name="Traish2018" /><ref name="pmid28319231" /> The absolute increase in the rate of depression was 247 per 100,000 patient-years and of self-harm was 17 per 100,000 patient-years.<ref name="pmid28319231" /><ref name="pmid28319227">{{cite journal | vauthors = Thielke S | title = The Risk of Suicidality and Depression From 5-α Reductase Inhibitors | journal = JAMA Intern Med | volume = 177 | issue = 5 | pages = 691–692 | year = 2017 | pmid = 28319227 | doi = 10.1001/jamainternmed.2017.0096 }}</ref> As such, on the basis of these findings, it has been stated that cases of depression in patients that are attributable to 5-ARIs will be encountered on occasion, while cases of self-harm attributable to 5-ARIs will be encountered very rarely.<ref name="pmid28319227" /> There were no differences in the rates of depression, self-harm, and suicide between finasteride and dutasteride, suggesting that the specific 5-ARI used does not influence the risks.<ref name="pmid30651009" /><ref name="pmid28319231" /><ref name="pmid28319227" /> The absolute risks of self-harm and depression with 5-ARIs remain low (0.14% and 2.0%, respectively).<ref name="pmid29449167">{{cite journal | vauthors = Malde S, Cartwright R, Tikkinen KA | title = What's New in Epidemiology? | journal = Eur Urol Focus | volume = 4 | issue = 1 | pages = 11–13 | date = January 2018 | pmid = 29449167 | doi = 10.1016/j.euf.2018.02.003 }}</ref> ==Pharmacology== The pharmacology of 5α-reductase inhibition is complex, but involves the binding of [[NADPH]] to the enzyme followed by the substrate. Specific substrates include [[testosterone]], [[progesterone]], [[androstenedione]], [[epitestosterone]], [[cortisol]], [[aldosterone]], and [[deoxycorticosterone]]. The entire physiologic effect of their reduction is unknown, but likely related to their excretion or is itself physiologic.<ref name="pmid22235201" /> 5α-Reductase reduces the steroid Δ<sup>4,5</sup> double bond in testosterone to its more active form DHT. Thus, inhibition results in decreased amounts of DHT. Because of this, slight elevations in testosterone and estradiol levels occur.<ref name=":1">{{Cite journal|last=Andersson|first=S.|date=July 2001|title=Steroidogenic enzymes in skin|journal=European Journal of Dermatology|volume=11|issue=4|pages=293–295|issn=1167-1122|pmid=11399532}}</ref> The 5α-reductase reaction is a rate-limiting step in the testosterone reduction and involves the binding of [[NADPH]] to the enzyme followed by the substrate.<ref name="pmid22235201">{{cite journal|display-authors=etal|year=2012|title=The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases|journal=Adv. Urol.|volume=2012|page=530121|doi=10.1155/2012/530121|pmc=3253436|pmid=22235201|vauthors=Azzouni F, Godoy A, Li Y, Mohler J|doi-access=free}}</ref><ref name="pmid16834758">{{Cite journal|last1=Finn|first1=Deborah A.|last2=Beadles-Bohling|first2=Amy S.|last3=Beckley|first3=Ethan H.|last4=Ford|first4=Matthew M.|last5=Gililland|first5=Katherine R.|last6=Gorin-Meyer|first6=Rebecca E.|last7=Wiren|first7=Kristine M.|date=2006|title=A new look at the 5alpha-reductase inhibitor finasteride|journal=CNS Drug Reviews|volume=12|issue=1|pages=53–76|doi=10.1111/j.1527-3458.2006.00053.x|issn=1080-563X|pmid=16834758|pmc=6741762}}</ref> ::: ''Substrate + NADPH + H<sup>+</sup> → 5α-substrate + NADP<sup>+</sup>'' Beyond being a catalyst in the [[rate-limiting step]] in testosterone reduction, 5α-reductase isoforms I and II reduce progesterone to [[5α-dihydroprogesterone]] (5α-DHP) and deoxycorticosterone to [[dihydrodeoxycorticosterone]] (DHDOC). In vitro and animal models suggest subsequent 3α-reduction of DHT, 5α-DHP and DHDOC lead to neurosteroid metabolites with effect on cerebral function. These [[neurosteroid]]s, which include [[allopregnanolone]], [[tetrahydrodeoxycorticosterone]] (THDOC), and [[3α-androstanediol]], act as potent [[positive allosteric modulator]]s of [[GABAA receptor|GABA<sub>A</sub> receptors]], and have [[antidepressant]], [[anxiolytic]], [[aphrodisiac|prosexual]], and [[anticonvulsant]] effects.<ref>{{Cite journal | last1 = Finn | first1 = D. A. | last2 = Beadles-Bohling | first2 = A. S. | last3 = Beckley | first3 = E. H. | last4 = Ford | first4 = M. M. | last5 = Gililland | first5 = K. R. | last6 = Gorin-Meyer | first6 = R. E. | last7 = Wiren | first7 = K. M. | doi = 10.1111/j.1527-3458.2006.00053.x | title = A New Look at the 5?-Reductase Inhibitor Finasteride | journal = CNS Drug Reviews | volume = 12 | issue = 1 | pages = 53–76 | year = 2006 | pmid = 16834758 | pmc = 6741762}}</ref> [[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 | vauthors = Weinstein BI, Kandalaft N, Ritch R, Camras CB, Morris DJ, Latif SA, Vecsei P, Vittek J, Gordon GG, Southren AL | title = 5 alpha-dihydrocortisol in human aqueous humor and metabolism of cortisol by human lenses in vitro | journal = Invest. Ophthalmol. Vis. Sci. | volume = 32 | issue = 7 | pages = 2130–5 |date=June 1991 | pmid = 2055703 }}</ref> [[5α-Dihydroaldosterone]] is a potent [[antidiuretic|antinatriuretic]] agent, although different from [[aldosterone]]. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium.<ref name="Kenyon_1983">{{cite journal | vauthors = 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> 5α-DHP is a major hormone in circulation of normal cycling and pregnant women.<ref name="pmid914969">{{cite journal | vauthors = 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 = J. Clin. Endocrinol. Metab. | volume = 45 | issue = 4 | pages = 617–22 |date=October 1977 | pmid = 914969 | doi =10.1210/jcem-45-4-617 | doi-access = free }}</ref> Other enzymes compensate to a degree for the absent conversion of 5α-reductase, specifically with local expression at the skin of reductive [[17β-hydroxysteroid dehydrogenase]], and oxidative [[3α-hydroxysteroid dehydrogenase]] and [[3β-hydroxysteroid dehydrogenase]] enzymes.<ref>{{Cite journal | last1 = Andersson | first1 = S. | title = Steroidogenic enzymes in skin | journal = European Journal of Dermatology | volume = 11 | issue = 4 | pages = 293–295 | year = 2001 | pmid = 11399532}}</ref> In BPH, DHT acts as a potent cellular androgen and promotes [[prostate]] growth; therefore, DHT blockers inhibit and alleviate symptoms of BPH. In alopecia, male and female-pattern baldness is an effect of androgenic receptor activation, so reducing levels of DHT also reduces hair loss. ==History== Finasteride was the first 5-ARI to be introduced for medical use.<ref name="BurgerAbraham2003">{{cite book|author1=Alfred Burger|author2=Donald J. Abraham|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=24 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 marketed for the treatment of BPH in 1992 and was subsequently approved for the treatment of pattern hair loss in 1997.<ref name="BurgerAbraham2003" /> Epristeride was the second 5-ARI to be introduced and was marketed for the treatment of BPH in [[China]] in 2000.<ref name="AdisInsight-Epristeride" /> Dutasteride was approved for the treatment of BPH in 2001 and was subsequently approved for pattern hair loss in [[South Korea]] in 2009 and in [[Japan]] in 2015.<ref name="Llewellyn2011">{{cite book|author=William Llewellyn|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT971|year=2011|publisher=Molecular Nutrition Llc|isbn=978-0-9828280-1-4|pages=968–,971–|access-date=2017-12-24|archive-date=2023-01-12|archive-url=https://web.archive.org/web/20230112145743/https://books.google.com/books?id=afKLA-6wW0oC&pg=PT971|url-status=live}}</ref><ref name="MacDonald">{{cite web|last1=MacDonald|first1=Gareth|title=GSK Japan delays alopecia drug launch after Catalent manufacturing halt|date=3 December 2015|url=http://www.in-pharmatechnologist.com/Regulatory-Safety/GSK-Japan-delays-alopecia-drug-launch-after-Catalent-manufacturing-halt|access-date=24 December 2017|archive-date=1 October 2016|archive-url=https://web.archive.org/web/20161001165059/http://www.in-pharmatechnologist.com/Regulatory-Safety/GSK-Japan-delays-alopecia-drug-launch-after-Catalent-manufacturing-halt|url-status=live}}</ref> The [[patent protection]] on finasteride and dutasteride has expired and both drugs are available as [[generic drug|generic medication]]s.<ref name="SataloffSclafani2015">{{cite book|author1=Robert T Sataloff|author2=Anthony P Sclafani|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=24 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><ref name="Drugs.com-Dutasteride">{{Cite web|url=https://www.drugs.com/availability/generic-avodart.html|title=Generic Avodart Availability|access-date=2017-12-24|archive-date=2016-12-20|archive-url=https://web.archive.org/web/20161220231141/https://www.drugs.com/availability/generic-avodart.html|url-status=live}}</ref> ==Research== 5-ARIs have been studied in combination with the [[nonsteroidal antiandrogen]] [[bicalutamide]] for the treatment of prostate cancer.<ref name="pmid15138573">{{cite journal |vauthors=Wang LG, Mencher SK, McCarron JP, Ferrari AC |title=The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review |journal=Oncology Reports |volume=11 |issue=6 |pages=1325–9 |year=2004 |pmid=15138573 |doi= 10.3892/or.11.6.1325}}</ref><ref name="pmid15151957">{{cite journal |vauthors=Tay MH, Kaufman DS, Regan MM, Leibowitz SB, George DJ, Febbo PG, Manola J, Smith MR, Kaplan ID, Kantoff PW, Oh WK |title=Finasteride and bicalutamide as primary hormonal therapy in patients with advanced adenocarcinoma of the prostate |journal=Annals of Oncology |volume=15 |issue=6 |pages=974–8 |year=2004 |pmid=15151957 |doi=10.1093/annonc/mdh221 |doi-access=free }}</ref><ref name="pmid16844453">{{cite journal |vauthors=Merrick GS, Butler WM, Wallner KE, Galbreath RW, Allen ZA, Kurko B |title=Efficacy of neoadjuvant bicalutamide and dutasteride as a cytoreductive regimen before prostate brachytherapy |journal=Urology |volume=68 |issue=1 |pages=116–20 |year=2006 |pmid=16844453 |doi=10.1016/j.urology.2006.01.061 }}</ref><ref name="pmid19796455">{{cite journal |vauthors=Sartor O, Gomella LG, Gagnier P, Melich K, Dann R |title=Dutasteride and bicalutamide in patients with hormone-refractory prostate cancer: the Therapy Assessed by Rising PSA (TARP) study rationale and design |journal=The Canadian Journal of Urology |volume=16 |issue=5 |pages=4806–12 |year=2009 |pmid=19796455 }}</ref><ref name="pmid26048455">{{cite journal |vauthors=Chu FM, Sartor O, Gomella L, Rudo T, Somerville MC, Hereghty B, Manyak MJ |title=A randomised, double-blind study comparing the addition of bicalutamide with or without dutasteride to GnRH analogue therapy in men with non-metastatic castrate-resistant prostate cancer |journal=European Journal of Cancer |volume=51 |issue=12 |pages=1555–69 |year=2015 |pmid=26048455 |doi=10.1016/j.ejca.2015.04.028 }}</ref><ref name="pmid26702991">{{cite journal |vauthors=Gaudet M, Vigneault É, Foster W, Meyer F, Martin AG |title=Randomized non-inferiority trial of Bicalutamide and Dutasteride versus LHRH agonists for prostate volume reduction prior to I-125 permanent implant brachytherapy for prostate cancer |journal=Radiotherapy and Oncology |volume=118 |issue=1 |pages=141–7 |year=2016 |pmid=26702991 |doi=10.1016/j.radonc.2015.11.022 }}</ref><ref name="pmid27330919">{{cite journal |vauthors=Dijkstra S, Witjes WP, Roos EP, Vijverberg PL, Geboers AD, Bruins JL, Smits GA, Vergunst H, Mulders PF |title=The AVOCAT study: Bicalutamide monotherapy versus combined bicalutamide plus dutasteride therapy for patients with locally advanced or metastatic carcinoma of the prostate-a long-term follow-up comparison and quality of life analysis |journal=SpringerPlus |volume=5 |pages=653 |year=2016 |pmid=27330919 |pmc=4870485 |doi=10.1186/s40064-016-2280-8 |doi-access=free }}</ref> ==See also== * [[List of 5α-reductase inhibitors]] * [[Discovery and development of 5α-reductase inhibitors]] * [[CYP17A1 inhibitor]] * [[Neurosteroidogenesis inhibitor]] ==References== {{Reflist|30em}} {{Enzyme inhibition}} {{Drugs used in benign prostatic hypertrophy}} {{Other dermatological preparations}} {{Androgens and antiandrogens}} [[Category:5α-Reductase inhibitors| ]] [[Category:Hair loss medications]] [[Category:Hair removal]] [[Category:Antiandrogens]] </textarea><div class="templatesUsed"><div class="mw-templatesUsedExplanation"><p><span id="templatesused">Pages transcluded onto the current version of this page<span class="posteditwindowhelplinks"> (<a href="/wiki/Help:Transclusion" title="Help:Transclusion">help</a>)</span>:</span> </p></div><ul> <li><a href="/wiki/Template:5%CE%B1-Reductase_inhibitors_marketed_for_clinical_or_veterinary_use" title="Template:5α-Reductase inhibitors marketed for clinical or 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