5α-Reductase inhibitor#Side effects

5-ARIs are clinically used in the treatment of conditions that are exacerbated by DHT:Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. {{ISBN|0-9578521-4-2}}

• 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. The usefulness of 5-ARIs for the potential treatment of acne is uncertain. 5-ARIs are sometimes used as antiandrogens in feminizing hormone therapy for transgender women to help reduce body hair growth and scalp hair loss.

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.{{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}}

Finasteride (brand names Proscar, Propecia) inhibits the function of two of the isoenzymes (types 2 and 3) of 5α-reductase.{{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 }}{{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}} It decreases circulating DHT levels by up to about 70%.{{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}} Dutasteride (brand name Avodart) inhibits all three 5α-reductase isoenzymes and can decrease DHT levels by 95%.{{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}}{{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 }} It can also reduce DHT levels in the prostate by 97 to 99% in men with prostate cancer.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,"{{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 }} Epristeride (brand names Aipuliete, Chuanliu) is marketed in China for the treatment of benign prostatic hyperplasia.{{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}}{{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}}{{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}} However, it can only decrease circulating DHT levels by about 25 to 54%.{{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–}} Alfatradiol (brand names Ell-Cranell Alpha, Pantostin) is a topical 5-ARI used to treat pattern hair loss in Europe.{{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}}{{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}}

{{5α-Reductase inhibitors marketed for clinical or veterinary use}}

5-ARIs are generally well tolerated in both men and women and produce few side effects.{{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 }}{{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 }} However, they have been found to have some risks in studies with men, including slightly increased risks of decreased libido, erectile dysfunction, ejaculatory dysfunction, infertility, breast tenderness, gynecomastia, depression, anxiety, self-harm, and dementia.{{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 }}{{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}} 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. 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.{{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 }} Finasteride has also been associated with intraoperative floppy iris syndrome and cataract formation.{{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 }}{{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 }} Depressive symptoms and suicidality have been reported.{{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}}

Sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride.{{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}} This is linked to lower quality of life and can cause stress in relationships.{{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}} There is also an association with lowered sexual desire.{{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}} It has been reported that in a subset of men, these adverse sexual side effects may persist even after discontinuation of finasteride or dutasteride.

5-ARIs have a small risk of breast changes in men including breast tenderness and gynecomastia (breast development/enlargement). The risk of gynecomastia is about 1.3%. There is no association of 5-ARIs with male breast cancer.{{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 }}

A 2017 population-based, matched-cohort study of 93,197 men aged 66 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 months of treatment, but were not associated with an increased risk of suicide (HR, 0.88; 95% CI, 0.53–1.45).{{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 }}{{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}}{{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 }} After the initial 18 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). 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.{{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 }} 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. 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. The absolute risks of self-harm and depression with 5-ARIs remain low (0.14% and 2.0%, respectively).{{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 }}

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. 5α-Reductase reduces the steroid Δ^4,5 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.{{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}} 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.{{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}}{{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}}

::: Substrate + NADPH + H⁺ → 5α-substrate + NADP⁺

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 neurosteroids, which include allopregnanolone, tetrahydrodeoxycorticosterone (THDOC), and 3α-androstanediol, act as potent positive allosteric modulators of GABA_A receptors, and have antidepressant, anxiolytic, prosexual, and anticonvulsant effects.{{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}} 5α-Dihydrocortisol is present in the aqueous humor of the eye, is synthesized in the lens, and might help make the aqueous humor itself.{{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 }} 5α-Dihydroaldosterone is a potent antinatriuretic agent, although different from aldosterone. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium.{{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 }} 5α-DHP is a major hormone in circulation of normal cycling and pregnant women.{{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 }}

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.{{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}}

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.

Finasteride was the first 5-ARI to be introduced for medical use.{{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}} It was marketed for the treatment of BPH in 1992 and was subsequently approved for the treatment of pattern hair loss in 1997. Epristeride was the second 5-ARI to be introduced and was marketed for the treatment of BPH in China in 2000. 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.{{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}}{{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}} The patent protection on finasteride and dutasteride has expired and both drugs are available as generic medications.{{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}}{{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}}

5-ARIs have been studied in combination with the nonsteroidal antiandrogen bicalutamide for the treatment of prostate cancer.{{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}}{{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 }}{{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 }}{{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 }}{{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 }}{{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 }}{{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 }}

• List of 5α-reductase inhibitors
• Discovery and development of 5α-reductase inhibitors
• CYP17A1 inhibitor
• Neurosteroidogenesis inhibitor

{{Reflist|30em}}

{{Enzyme inhibition}}

{{Drugs used in benign prostatic hypertrophy}}

{{Other dermatological preparations}}

{{Androgens and antiandrogens}}

Category:Hair loss medications

Category:Hair removal

Category:Antiandrogens