dutasteride

Dutasteride is used for treating BPH, colloquially known as an "enlarged prostate".{{Cite journal |vauthors=Slater S, Dumas C, Bubley G |date=March 2012 |title=Dutasteride for the treatment of prostate-related conditions |journal=Expert Opinion on Drug Safety |volume=11 |issue=2 |pages=325–330 |doi=10.1517/14740338.2012.658040 |pmid=22316171 |s2cid=207487490}} It is approved by the Food and Drug Administration (FDA) in the U.S. for this indication.{{Cite web |title=Search Results for "DUTASTERIDE" |url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=021319&DrugName=AVODART&ActiveIngred=DUTASTERIDE&SponsorApplicant=GLAXOSMITHKLINE&ProductMktStatus=1&goto=Search.DrugDetails |url-status=dead |archive-url=https://web.archive.org/web/20210829124132/https://www.accessdata.fda.gov/scripts/cder/daf/ |archive-date=2021-08-29 |access-date=2016-10-29 |website=Drugs@FDA: FDA Approved Drug Products}} A 2010 Cochrane review found a 25–26% reduction in the risk of developing prostate cancer with 5α-reductase inhibitor chemoprevention.{{Cite journal |vauthors=Wilt TJ, Macdonald R, Hagerty K, Schellhammer P, Tacklind J, Somerfield MR, Kramer BS |date=November 2010 |title=5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review |journal=BJU International |volume=106 |issue=10 |pages=1444–1451 |doi=10.1111/j.1464-410X.2010.09714.x |pmid=20977593 |s2cid=22178061}}

Dutasteride is approved for the treatment of male androgenetic alopecia in South Korea and Japan at a dosage of 0.5 mg per day. Several studies have found it to induce hair regrowth in men more rapidly and to a greater extent than even the highest approved dosage of finasteride.{{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 |date=May 2020 |title=5-Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms, current concepts, comparative efficacy, and safety |journal=Dermatologic Therapy |volume=33 |issue=3 |pages=e13379 |doi=10.1111/dth.13379 |pmid=32279398 |s2cid=215748750 |doi-access=free}}{{Cite journal |vauthors=Zhou Z, Song S, Gao Z, Wu J, Ma J, Cui Y |date=2019 |title=The efficacy and safety of dutasteride compared with finasteride in treating men with androgenetic alopecia: a systematic review and meta-analysis |journal=Clinical Interventions in Aging |volume=14 |pages=399–406 |doi=10.2147/CIA.S192435 |pmc=6388756 |pmid=30863034 |doi-access=free}}{{Cite journal |vauthors=Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, Wilson T, Rittmaster RS |date=December 2006 |title=The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride |journal=Journal of the American Academy of Dermatology |volume=55 |issue=6 |pages=1014–1023 |doi=10.1016/j.jaad.2006.05.007 |pmid=17110217}} The superior effectiveness of dutasteride relative to finasteride for this indication is because the inhibition of 5α-reductase and consequent reduction of dihydrotestosterone (DHT) production within the hair follicles is more complete with dutasteride. Dutasteride is also used off-label in the treatment of female pattern hair loss.{{Cite journal |vauthors=Carmina E, Azziz R, Bergfeld W, Escobar-Morreale HF, Futterweit W, Huddleston H, Lobo R, Olsen E |date=July 2019 |title=Female Pattern Hair Loss and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee |journal=The Journal of Clinical Endocrinology and Metabolism |volume=104 |issue=7 |pages=2875–2891 |doi=10.1210/jc.2018-02548 |pmid=30785992 |doi-access=free}}

Other 5α-reductase inhibitors such as finasteride (a type 2 inhibitor) have been used off-label to treat excessive hair growth in women with hirsutism.{{Cite journal |vauthors=Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA |date=April 2008 |title=Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline |journal=The Journal of Clinical Endocrinology and Metabolism |volume=93 |issue=4 |pages=1105–1120 |doi=10.1210/jc.2018-00241 |pmid=18252793 |doi-access=free}} Since dutasteride is an inhibitor of both type 1 and 2 5α-reductases, it could theoretically be a more effective therapy for hirsutism. However, dutasteride is not recommended for this indication due to a lack of supportive clinical evidence and a substantial risk of birth defects in female patients who inadvertently become pregnant.{{Cite book |url=https://books.google.com/books?id=hRryAAAAQBAJ&pg=PA327 |title=Treatment of Skin Disease: Comprehensive Therapeutic Strategies |vauthors=Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I |date=19 September 2013 |publisher=Elsevier Health Sciences |isbn=978-0-7020-5236-1 |pages=327– |access-date=10 December 2016 |archive-url=https://web.archive.org/web/20230112145741/https://books.google.com/books?id=hRryAAAAQBAJ&pg=PA327 |archive-date=12 January 2023 |url-status=live}}

Dutasteride is sometimes used as a component of hormone therapy for transgender women in combination with an estrogen and/or another antiandrogen such as spironolactone. It may be useful for preventing and treating scalp hair loss and can also be used as a general antiandrogen for in those who have issues tolerating spironolactone, though as a α-reductase inhibitor it has limited effects compared to AR antagonists.

Dutasteride is provided in the form of soft, oil-filled gelatin capsules containing 0.5 mg dutasteride each.

Women who are or who may become pregnant should not handle the drug. Dutasteride can cause birth defects in male fetuses, specifically ambiguous genitalia and undermasculinization.{{Cite book |url=https://books.google.com/books?id=OkLUDAAAQBAJ&pg=PA396 |title=Treatment of Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: Current methods, outcomes, and controversies, An Issue of Urologic Clinics of North America, E-Book |vauthors=McVary KT, Welliver C |date=12 August 2016 |publisher=Elsevier Health Sciences |isbn=978-0-323-45994-5 |pages=396– |access-date=10 December 2017 |archive-url=https://web.archive.org/web/20230112145741/https://books.google.com/books?id=OkLUDAAAQBAJ&pg=PA396 |archive-date=12 January 2023 |url-status=live}} This is due to its antiandrogenic effects similar to what is seen in 5α-reductase deficiency. For the same reason, women who are currently pregnant should never take dutasteride. People taking dutasteride should not donate blood to prevent birth defects if a pregnant woman receives blood and should also not donate blood for at least 6 months after the cessation of treatment due to the drug's long elimination half-life.

Children and people with known significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride should not take it.{{Cite web |last= |date=June 2011 |title=AVODART (dutasteride) Soft Gelatin Capsules Prescribing information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021319s023s025lbl.pdf |url-status=live |archive-url=https://web.archive.org/web/20130307020555/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021319s023s025lbl.pdf |archive-date=7 March 2013 |access-date=15 September 2013 |website=GlaxoSmithKline |publisher=U.S. Food and Drug Administration}}

Dutasteride has overall been found to be well tolerated in studies of both men and women, producing minimal side effects.{{Cite journal |vauthors=Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS |date=July 2016 |title=Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review |journal=The Journal of Clinical and Aesthetic Dermatology |volume=9 |issue=7 |pages=56–62 |pmc=5023004 |pmid=27672412}} Adverse effects include headache and gastrointestinal discomfort. Isolated reports of menstrual changes, acne, and dizziness also exist. A small risk of sexual side effects has been documented in men taking the drug during the first few months of therapy.{{Cite journal |vauthors=Trost L, Saitz TR, Hellstrom WJ |date=May 2013 |title=Side Effects of 5-Alpha Reductase Inhibitors: A Comprehensive Review |journal=Sexual Medicine Reviews |volume=1 |issue=1 |pages=24–41 |doi=10.1002/smrj.3 |pmid=27784557}}

The FDA added a black-box warning to dutasteride in 2011 describing an increased risk of high-grade prostate cancer in those who take the drug.{{Cite web |date=18 June 2019 |title=FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-5-alpha-reductase-inhibitors-5-aris-may-increase-risk-more-serious |url-status=live |archive-url=https://web.archive.org/web/20210309192037/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-5-alpha-reductase-inhibitors-5-aris-may-increase-risk-more-serious |archive-date=9 March 2021 |access-date=9 March 2021 |newspaper=U.S. Food and Drug Administration}} No direct mechanistic link between 5α-reductase inhibitors and prostate cancer has been established. This is not due to a direct link between dutasteride or other 5α-reductase inhibitors and cancer per se, but rather that those who take 5α-reductase inhibitors may have a decrease in prostate-specific antigen (PSA) levels, and therefore increases in PSA (which are an indicator of possible cancer) may be masked in those who take the drug.{{Cite journal |vauthors=Sarkar RR, Parsons JK, Bryant AK, Ryan ST, Kader AK, McKay RR, D'Amico AV, Nguyen PL, Hulley BJ, Einck JP, Mundt AJ, Kane CJ, Murphy JD, Rose BS |date=June 2019 |title=Association of Treatment With 5α-Reductase Inhibitors With Time to Diagnosis and Mortality in Prostate Cancer |journal=JAMA Internal Medicine |volume=179 |issue=6 |pages=812–819 |doi=10.1001/jamainternmed.2019.0280 |pmc=6503564 |pmid=31058923}} This is thought to delay cancer diagnosis so that patients taking 5α-reductase inhibitors present with a higher-grade tumor at the time of diagnosis. The American Urological Association advises that increased risk for patients taking these drugs leads to higher prostate cancer-specific and all-cause mortality.{{Cite journal |vauthors=Lerner LB, McVary KT, Barry MJ, Bixler BR, Dahm P, Das AK, Gandhi MC, Kaplan SA, Kohler TS, Martin L, Parsons JK, Roehrborn CG, Stoffel JT, Welliver C, Wilt TJ |date=October 2021 |title=Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART I-Initial Work-up and Medical Management |journal=The Journal of Urology |volume=206 |issue=4 |pages=806–817 |doi=10.1097/JU.0000000000002183 |pmid=34384237 |s2cid=236999299}} The AUA also advises that this affect can be alleviated with more frequent screening and lower PSA cutoffs for diagnostic biopsies in men taking dutasteride or other 5α-reductase inhibitors. Dutasteride is known to reduce the growth and prevalence of benign prostate tumors.{{Cite journal |vauthors=Walsh PC |date=April 2010 |title=Chemoprevention of prostate cancer |journal=The New England Journal of Medicine |volume=362 |issue=13 |pages=1237–1238 |doi=10.1056/NEJMe1001045 |pmid=20357287}} A 2018 meta-analysis found no higher risk of breast cancer with 5α-reductase inhibitors.{{Cite journal |vauthors=Wang J, Zhao S, Luo L, Li E, Li X, Zhao Z |date=2018 |title=5-alpha Reductase Inhibitors and risk of male breast cancer: a systematic review and meta-analysis |journal=International Braz J Urol |volume=44 |issue=5 |pages=865–873 |doi=10.1590/S1677-5538.IBJU.2017.0531 |pmc=6237523 |pmid=29697934}}

Sexual and mood side effects, such as erectile dysfunction,{{Cite journal |vauthors=Fertig R, Shapiro J, Bergfeld W, Tosti A |date=January 2017 |title=Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome |journal=Skin Appendage Disorders |volume=2 |issue=3–4 |pages=120–129 |doi=10.1159/000450617 |pmc=5264352 |pmid=28232919}} loss of libido,{{Cite journal |vauthors=Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M |date=September 2015 |title=Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know? |journal=Reviews in Endocrine & Metabolic Disorders |volume=16 |issue=3 |pages=177–198 |doi=10.1007/s11154-015-9319-y |pmid=26296373 |s2cid=25002351}} depression,{{Cite journal |vauthors=Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML |date=March 2011 |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=872–884 |doi=10.1111/j.1743-6109.2010.02157.x |pmid=21176115}} and reduced semen volume occur in as many as 4.8% of patients taking 5α-reductase inhibitors including dutasteride.{{Cite journal |vauthors=Traish AM, Mulgaonkar A, Giordano N |date=June 2014 |title=The dark side of 5α-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression |journal=Korean Journal of Urology |volume=55 |issue=6 |pages=367–379 |doi=10.4111/kju.2014.55.6.367 |pmc=4064044 |pmid=24955220}} In affected men, semen volume is decreased an average of 30%,{{Cite journal |vauthors=Samplaski MK, Lo K, Grober E, Jarvi K |date=December 2013 |title=Finasteride use in the male infertility population: effects on semen and hormone parameters |journal=Fertility and Sterility |volume=100 |issue=6 |pages=1542–1546 |doi=10.1016/j.fertnstert.2013.07.2000 |pmid=24012200 |doi-access=free}} with a smaller subgroup of patients also experiencing a decrease of sperm motility of 6 to 12%.{{Cite journal |vauthors=Amory JK, Wang C, Swerdloff RS, Anawalt BD, Matsumoto AM, Bremner WJ, Walker SE, Haberer LJ, Clark RV |date=May 2007 |title=The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men |journal=The Journal of Clinical Endocrinology and Metabolism |volume=92 |issue=5 |pages=1659–1665 |doi=10.1210/jc.2006-2203 |pmid=17299062}} Sperm shape and function are unaffected and the impact on male fertility is unknown.{{Cite journal |vauthors=Semet M, Paci M, Saïas-Magnan J, Metzler-Guillemain C, Boissier R, Lejeune H, Perrin J |date=July 2017 |title=The impact of drugs on male fertility: a review |journal=Andrology |volume=5 |issue=4 |pages=640–663 |doi=10.1111/andr.12366 |pmid=28622464 |s2cid=37989045 |doi-access=free}} These negative effects reverse by 3–4 months after discontinuation of the drug.{{Cite journal |vauthors=Millsop JW, Heller MM, Eliason MJ, Murase JE |date=July 2013 |title=Dermatological medication effects on male fertility |journal=Dermatologic Therapy |volume=26 |issue=4 |pages=337–346 |doi=10.1111/dth.12069 |pmid=23914891 |s2cid=9087715 |doi-access=free}}

In a study of 6,729 men with benign prostatic hyperplasia (BPH, a condition where the prostate grows unassociated with cancer), 9% had erectile dysfunction (compared to 5.7% treated with a placebo), 3.3% experienced decreased sex drive (vs 1.6% of placebo), and 1.9% had enlarged breasts (vs 1% of placebo). These effects were noted to resolve over time, with many fewer men reporting any adverse effects by the end of the 4-year study. The rate of discontinuation of the drug due to adverse effects was less than 5%.

A subset of men affected by sexual and mood side effects report persistent loss of libido, depression, and erectile dysfunction for several years after discontinuing treatment. This remains a highly contested topic in the academic literature due to disagreements about whether the nocebo effect may play a role,{{Cite journal |vauthors=Than JK, Rodriguez K, Khera M |date=24 July 2018 |title=Post-finasteride Syndrome: A Review of Current Literature |journal=Current Sexual Health Reports |volume=10 |issue=3 |pages=152–157 |doi=10.1007/s11930-018-0163-4 |issn=1548-3584 |eissn=1548-3592 |s2cid=81968700}}{{Cite journal |vauthors=Saengmearnuparp T, Lojanapiwat B, Chattipakorn N, Chattipakorn S |date=November 2021 |title=The connection of 5-alpha reductase inhibitors to the development of depression |journal=Biomedicine & Pharmacotherapy |volume=143 |pages=112100 |doi=10.1016/j.biopha.2021.112100 |pmid=34479019 |doi-access=free}}{{Cite journal |vauthors=Coskuner ER, Ozkan B, Culha MG |date=April 2019 |title=Sexual Problems of Men With Androgenic Alopecia Treated With 5-Alpha Reductase Inhibitors |journal=Sexual Medicine Reviews |volume=7 |issue=2 |pages=277–282 |doi=10.1016/j.sxmr.2018.07.003 |pmid=30301703 |s2cid=52946784}} whether self-report questionnaires are reliable for this data, and whether enough objective evidence exists to conclude these effects are persistent after discontinuation of the drug.{{Cite journal |vauthors=Traish AM |date=January 2020 |title=Post-finasteride syndrome: a surmountable challenge for clinicians |journal=Fertility and Sterility |volume=113 |issue=1 |pages=21–50 |doi=10.1016/j.fertnstert.2019.11.030 |pmid=32033719 |s2cid=211064052 |doi-access=free}}{{Cite journal |vauthors=Liu L, Zhao S, Li F, Li E, Kang R, Luo L, Luo J, Wan S, Zhao Z |date=September 2016 |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 |volume=13 |issue=9 |pages=1297–1310 |doi=10.1016/j.jsxm.2016.07.006 |pmid=27475241}} The Post-Finasteride Syndrome Foundation (PFSF) was created with a medical advisory board to study the topic (finasteride is a similar 5α-reductase inhibitor){{Cite web |title=The Post-Finasteride Syndrome Foundation – Dedicated to supporting research and finding treatments for PFS patients worldwide. |url=https://www.pfsfoundation.org/ |url-status=live |archive-url=https://web.archive.org/web/20211221100527/https://www.pfsfoundation.org/ |archive-date=2021-12-21 |access-date=2021-12-24 |language=en-US}} and lawsuits alleging harm from the drug are ongoing.{{Cite news |date=2021-09-08 |title=Group sues to have hair-loss drug Propecia pulled from market |url=https://www.reuters.com/legal/litigation/group-sues-have-hair-loss-drug-propecia-pulled-market-2021-09-08/ |url-status=live |archive-url=https://web.archive.org/web/20211224165809/https://www.reuters.com/legal/litigation/group-sues-have-hair-loss-drug-propecia-pulled-market-2021-09-08/ |archive-date=2021-12-24 |access-date=2021-12-24 |work=Reuters |language=en |vauthors=Pierson B}} Concerns from the PFSF and other patient advocates led the FDA to add a black-box warning to Finasteride for possible risks of suicide in June 2022.{{Cite news |date=10 June 2022 |title=FDA requires disclosure of suicide risk for anti-baldness drug |url=https://www.reuters.com/business/healthcare-pharmaceuticals/fda-requires-disclosure-suicide-risk-anti-baldness-drug-2022-06-10/ |url-status=live |archive-url=https://web.archive.org/web/20221112200941/https://www.reuters.com/business/healthcare-pharmaceuticals/fda-requires-disclosure-suicide-risk-anti-baldness-drug-2022-06-10/ |archive-date=12 November 2022 |access-date=12 November 2022 |work=Reuters |language=en |vauthors=Levine D}} Some experts have questioned the basis of the black-box warning, given that it relies on anecdotal patient-reported outcomes rather than prospective trials.

No specific antidote for overdose of dutasteride is known, since the drug is extremely safe and well tolerated. Research studies show that even at 100 times the normal dose, dutasteride is not lethal.{{Cite web |title=AVODART (dutasteride) Soft Gelatin Capsules Prescribing information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021319s028s029lbl.pdf |url-status=live |archive-url=https://web.archive.org/web/20210403220821/https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021319s028s029lbl.pdf |archive-date=2021-04-03 |access-date=2020-01-10 |website=GlaxoSmithKline |publisher=U.S. Food and Drug Administration}} Treatment of dutasteride overdose should be based on symptoms and should be with supportive therapies. The long elimination half-life of dutasteride should be taken into consideration in the event of an overdose of the medication. Dutasteride has been used in clinical studies at doses of up to 40 mg/day for a week (80 times the therapeutic dosage) and 5 mg/day for 6 months (10 times the therapeutic dosage) with no significant safety concerns or additional side effects.

Dutasteride has been studied in combination with bicalutamide in the treatment of prostate cancer.{{Cite journal |vauthors=Chu FM, Sartor O, Gomella L, Rudo T, Somerville MC, Hereghty B, Manyak MJ |date=August 2015 |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=1555–1569 |doi=10.1016/j.ejca.2015.04.028 |pmid=26048455}}{{Cite journal |vauthors=Gaudet M, Vigneault É, Foster W, Meyer F, Martin AG |date=January 2016 |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=141–147 |doi=10.1016/j.radonc.2015.11.022 |pmid=26702991}}{{Cite journal |vauthors=Dijkstra S, Witjes WP, Roos EP, Vijverberg PL, Geboers AD, Bruins JL, Smits GA, Vergunst H, Mulders PF |year=2016 |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 |doi=10.1186/s40064-016-2280-8 |pmc=4870485 |pmid=27330919 |doi-access=free}}

Ongoing clinical trials are investigating whether dutasteride may be an effective treatment for premenstrual dysphoric disorder (PMDD), because dutasteride may inhibit the conversion of progesterone to allopregnanolone, a neurosteroid metabolite, which may be responsible for some of the debilitating symptoms of PMDD.{{Cite journal |vauthors=Pearlstein T |date=April 2016 |title=Treatment of Premenstrual Dysphoric Disorder: Therapeutic Challenges |journal=Expert Review of Clinical Pharmacology |volume=9 |issue=4 |pages=493–496 |doi=10.1586/17512433.2016.1142371 |pmid=26766596 |quote=A recent study with a 5α-reductase inhibitor dutasteride, that blocks the conversion of progesterone to ALLO, reported that dutasteride 2.5 mg daily decreased several premenstrual symptoms |doi-access=free}}{{Cite journal |vauthors=Naguy A, El-Sheshai A, Thiguti SH, Alamiri B |date=June 2022 |title=Psychopharmacotherapy of Premenstrual Dysphoric Disorder-New Vistas |journal=Psychopharmacology Bulletin |volume=52 |issue=3 |pages=81–83 |pmc=9235312 |pmid=35815174 |quote=Capitalizing on this premise, agents in the pipeline for PMDD including dutasteride, ulipristal acetate, and sepranolone are promising. Dutasteride, FDA-approved for benign prostatic hyperplasia, is a 5-α reductase inhibitor; the latter catalyzes the rate-limiting step in metabolism of progesterone to allopregnanolone...Two double-blind RCTs, cross-over trials, support use of dutasteride where high-dose (2.5 mg/d) outperforms placebo.}}

Dutasteride belongs to a class of drugs called 5α-reductase inhibitors, which block the action of the 5α-reductase enzymes that convert testosterone into DHT.{{Cite book |url=https://books.google.com/books?id=wrHQAgAAQBAJ&pg=PA492 |title=Urologic Surgical Pathology |vauthors=Bostwick DG, Cheng L |date=24 January 2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-08619-6 |pages=492–}} It inhibits all three forms of 5α-reductase, and can decrease DHT levels in the blood by up to 98%.{{Cite book |url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1286 |title=Foye's Principles of Medicinal Chemistry |vauthors=Lemke TL, Williams DA |publisher=Lippincott Williams & Wilkins |year=2008 |isbn=978-0-7817-6879-5 |pages=1286–1287 |access-date=2017-12-06 |archive-url=https://web.archive.org/web/20230110031700/https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1286 |archive-date=2023-01-10 |url-status=live}}{{Cite journal |vauthors=Yamana K, Labrie F, Luu-The V |date=August 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 by 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}}{{Cite book |url=https://books.google.com/books?id=fdtDAAAAQBAJ&pg=PA49 |title=Cancer |vauthors=Bradbury R |date=30 January 2007 |publisher=Springer Science & Business Media |isbn=978-3-540-33120-9 |pages=49–}} Specifically it is a competitive, mechanism-based (irreversible) inhibitor of all three isoforms of 5α-reductase, types I, II, and III ({{abbrlink|IC₅₀|Half-maximal inhibitory concentration}} values are 3.9 nM for type I and 1.8 nM for type II).{{Cite journal |vauthors=Keam SJ, Scott LJ |year=2008 |title=Dutasteride: a review of its use in the management of prostate disorders |journal=Drugs |volume=68 |issue=4 |pages=463–485 |doi=10.2165/00003495-200868040-00008 |pmid=18318566 |s2cid=242987808}}{{Cite journal |vauthors=Gisleskog PO, Hermann D, Hammarlund-Udenaes M, Karlsson MO |date=December 1998 |title=A model for the turnover of dihydrotestosterone in the presence of the irreversible 5 alpha-reductase inhibitors GI198745 and finasteride |journal=Clinical Pharmacology and Therapeutics |volume=64 |issue=6 |pages=636–647 |doi=10.1016/S0009-9236(98)90054-6 |pmid=9871428 |s2cid=42901328}} This is in contrast to finasteride, which is similarly an irreversible inhibitor of 5α-reductase but only inhibits the type II and III isoenzymes.{{Cite book |url=https://books.google.com/books?id=7WpICgAAQBAJ&pg=PA165 |title=Thermodynamics and Kinetics of Drug Binding |vauthors=Keserü G, Swinney DC |date=28 July 2015 |publisher=Wiley |isbn=978-3-527-67304-9 |pages=165–}} As a result of this difference, dutasteride is able to achieve a reduction in circulating DHT levels of up to 98%, whereas finasteride is able to achieve a reduction of only 65 to 70%.{{Cite book |url=https://books.google.com/books?id=aWKhCwAAQBAJ&pg=PA280 |title=Practical Functional Urology |vauthors=Heesakkers J, Chapple C, De Ridder D, Farag F |date=24 February 2016 |publisher=Springer |isbn=978-3-319-25430-2 |pages=280–}} In spite of the differential reduction in circulating DHT levels, the two drugs decrease levels of DHT to a similar extent of approximately 85 to 90% in the prostate gland, where the type II isoform predominates.

Since 5α-reductases degrade testosterone to DHT, the inhibition of these enzymes could theoretically cause an increase in testosterone. A 2018 review found that initiation of 5α-reductase inhibitors did not result in a consistent increase in testosterone levels.{{Cite journal |vauthors=Traish AM, Krakowsky Y, Doros G, Morgentaler A |date=January 2019 |title=Do 5α-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results |journal=Sexual Medicine Reviews |volume=7 |issue=1 |pages=95–114 |doi=10.1016/j.sxmr.2018.06.002 |pmid=30098986 |s2cid=51968365}} Among the studies analyzed, there was no statistically significant change in testosterone levels from 5α-reductase inhibitors overall, though men with lower baseline testosterone levels did show an increase.

In addition to inhibition of DHT production, 5α-reductase inhibitors such as dutasteride are also neurosteroidogenesis inhibitors, preventing the 5α-reductase-mediated biosynthesis of various neurosteroids, including allopregnanolone (from progesterone), {{abbrlink|THDOC|tetrahydrodeoxycorticosterone}} (from deoxycorticosterone), and 3α-androstanediol (from testosterone). These neurosteroids are potent positive allosteric modulators of the GABA_A receptor and have shown antidepressant, anxiolytic, and pro-sexual effects in animal research.{{Cite book |url=https://books.google.com/books?id=uABKkFdPjhkC |title=Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment |vauthors=Weizman A |date=1 February 2008 |publisher=Springer Science & Business Media |isbn=978-1-4020-6854-6}}{{Cite journal |vauthors=Tvrdeić A, Poljak L |year=2016 |title=Neurosteroids, GABAA receptors and neurosteroid based drugs: are we witnessing the dawn of the new psychiatric drugs? |journal=Endocrine Oncology and Metabolism |volume=2 |issue=1 |pages=60–71 |doi=10.21040/eom/2016.2.7 |doi-broken-date=1 November 2024 |doi-access=free}} For this reason, decreased neurosteroid production is one hypothesized mechanism for sexual dysfunction and depression associated with 5α-reductase inhibitors such as dutasteride.

The oral bioavailability of dutasteride is about 60%. Consumption with food does not adversely affect its absorption. Peak plasma levels occur 2 to 3 hours after administration. Dutasteride is present in semen at levels up to 3 ng/ml, with no significant effects on DHT levels of sexual partners. The drug is extensively metabolized in the liver by CYP3A4. It has three major metabolites: 6'-hydroxydutasteride, 4'-hydroxydutasteride, and 1,2-dihydrodutasteride. The former two are formed by CYP3A4, while the latter is not. All three metabolites are active; 6'-hydroxydutasteride has similar 5α-reductase inhibitor potency as dutasteride, while the other two are less potent. Dutasteride has an extremely long terminal or elimination half-life of about 4 to 5 weeks.{{Cite book |url=https://books.google.com/books?id=C7_NBQAAQBAJ&pg=PA803 |title=Lehne's Pharmacology for Nursing Care |vauthors=Burchum J, Rosenthal L |date=2 December 2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-34026-7 |pages=803– |access-date=27 October 2016 |archive-url=https://web.archive.org/web/20230112145742/https://books.google.com/books?id=C7_NBQAAQBAJ&pg=PA803 |archive-date=12 January 2023 |url-status=live}} Its elimination half-life is increased in the elderly (170 hours for men aged 20–49 years, 300 hours for men aged >70 years). No dosage adjustment is necessary in the elderly nor in patients with renal impairment. Because of its long elimination half-life, dutasteride requires 5 to 6 months to reach steady-state concentrations. It also remains in the body for a long time after discontinuation and can be detected up to 4 to 6 months. In contrast to dutasteride, finasteride has a short terminal half-life of only 5 to 8 hours. Dutasteride is eliminated mainly in the feces (40%) as metabolites. A smaller portion (5%) is eliminated unchanged in the urine.

{{See also|List of 5α-reductase inhibitors}}

Dutasteride, also known as N-[2,5-bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, is a synthetic androstane steroid and a 4-azasteroid.{{Cite book |url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1381 |title=Foye's Principles of Medicinal Chemistry |vauthors=Lemke TL, Williams DA |date=24 January 2012 |publisher=Lippincott Williams & Wilkins |isbn=978-1-60913-345-0 |pages=1381–}}{{Cite book |url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA183 |title=The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs |vauthors=Ravina E |date=11 January 2011 |publisher=John Wiley & Sons |isbn=978-3-527-32669-3 |pages=183–}} It is an analogue of finasteride in which the tert-butyl amide moiety has been replaced with a 2,5-bis(trifluoromethyl)phenyl group.

Dutasteride was patented in 1996 and was first described in the scientific literature in 1997. It was approved by the FDA for the treatment of BPH in November 2001, and was introduced on the United States market the following year under the brand name Avodart. Dutasteride has subsequently been introduced in many other countries, including throughout Europe and South America.{{Cite book |url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT971 |title=Anabolics |vauthors=Llewellyn W |publisher=Molecular Nutrition Llc |year=2011 |isbn=978-0-9828280-1-4 |pages=968–,971– |access-date=2017-12-11 |archive-url=https://web.archive.org/web/20230112145743/https://books.google.com/books?id=afKLA-6wW0oC&pg=PT971 |archive-date=2023-01-12 |url-status=live}} The patent protection of dutasteride expired in November 2015, so the drug has since become available in the United States in a variety of low-cost generic formulations.{{Cite web |title=Generic Avodart Availability |url=https://www.drugs.com/availability/generic-avodart.html |url-status=live |archive-url=https://web.archive.org/web/20161220231141/https://www.drugs.com/availability/generic-avodart.html |archive-date=2016-12-20 |access-date=2016-12-10 |website=Drugs.com}}

It was approved for the treatment of scalp hair loss in South Korea in 2009 and in Japan in 2015.{{Cite web |date=3 December 2015 |title=GSK Japan delays alopecia drug launch after Catalent manufacturing halt |url=http://www.in-pharmatechnologist.com/Regulatory-Safety/GSK-Japan-delays-alopecia-drug-launch-after-Catalent-manufacturing-halt |url-status=live |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 |archive-date=1 October 2016 |access-date=14 June 2017 |vauthors=MacDonald G}} It has not been approved for this indication in the United States,{{Cite journal |vauthors=Choi GS, Kim JH, Oh SY, Park JM, Hong JS, Lee YS, Lee WS |date=August 2016 |title=Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in the Treatment of Androgenetic Alopecia |journal=Annals of Dermatology |volume=28 |issue=4 |pages=444–450 |doi=10.5021/ad.2016.28.4.444 |pmc=4969473 |pmid=27489426}} though it is often used off-label.{{Cite journal |vauthors=Nusbaum AG, Rose PT, Nusbaum BP |date=August 2013 |title=Nonsurgical therapy for hair loss |journal=Facial Plastic Surgery Clinics of North America |volume=21 |issue=3 |pages=335–342 |doi=10.1016/j.fsc.2013.04.003 |pmid=24017975}}

File:Avodart.jpg

Dutasteride is the generic name of the drug Avodart and its international nonproprietary name, United States Adopted Name, British Approved Name, and Japanese Accepted Name.{{Cite web |title=Dutasteride |url=https://www.drugs.com/international/dutasteride.html |url-status=live |archive-url=https://web.archive.org/web/20171211105304/https://www.drugs.com/international/dutasteride.html |archive-date=2017-12-11 |access-date=2017-12-11 |website=Drugs.com}}

Dutasteride is sold primarily under the brand name Avodart, but also in combination with tamsulosin under the brand names Combodart, Duodart, and Jalyn. Dutasteride is also available in India in combination with alfuzosin under the brand names Alfusin-D and Dutalfa.

Dutasteride is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, Europe, Australia, South Africa, Latin America, Asia, and elsewhere. It is available as a generic medication in many countries, including the United States.

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• {{Cite journal |vauthors=Frye SV |year=2006 |title=Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor |journal=Current Topics in Medicinal Chemistry |volume=6 |issue=5 |pages=405–421 |doi=10.2174/156802606776743101 |pmid=16719800}}

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