Dutasteride

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Dutasteride
Dutasteride.svg
Clinical data
Trade namesAvodart, others; Combodart, Duodart (with tamsulosin)
Other namesGG-745; GI-198745; GI-198745X; N-[2,5-Bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide
AHFS/Drugs.comMonograph
MedlinePlusa603001
License data
Pregnancy
category
  • Not to be used during pregnancy
Routes of
administration
By mouth
Drug class5α-Reductase inhibitor
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60%[1]
Protein binding99%[1]
MetabolismLiver (CYP3A4)[1]
Metabolites• 4'-Hydroxydutasteride[1]
• 6'-Hydroxydutasteride[1]
• 1,2-Dihydrodutasteride[1]
(All three active)[1]
Elimination half-life4–5 weeks[2][3]
ExcretionFeces: 40% (metabolites)[1]
Urine: 5% (unchanged)[1]
Identifiers
  • (1S,3aS,3bS,5aR,9aR,9bS,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.166.372 Edit this at Wikidata
Chemical and physical data
FormulaC27H30F6N2O2
Molar mass528.539 g·mol−1
3D model (JSmol)
  • FC(F)(F)c1cc(c(cc1)C(F)(F)F)NC(=O)[C@@H]3[C@]2(CC[C@H]4[C@H]([C@@H]2CC3)CC[C@H]5NC(=O)\C=C/[C@]45C)C
  • InChI=1S/C27H30F6N2O2/c1-24-11-9-17-15(4-8-21-25(17,2)12-10-22(36)35-21)16(24)6-7-19(24)23(37)34-20-13-14(26(28,29)30)3-5-18(20)27(31,32)33/h3,5,10,12-13,15-17,19,21H,4,6-9,11H2,1-2H3,(H,34,37)(H,35,36)/t15-,16-,17-,19+,21+,24-,25+/m0/s1 checkY
  • Key:JWJOTENAMICLJG-QWBYCMEYSA-N checkY
  (verify)

Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of an enlarged prostate. A few months may be required before benefits occur.[4] It is also used for scalp hair loss in men and as a part of hormone therapy in transgender women.[5][6] It is taken orally.[7][8][4]

The most commonly reported side effects of dutasteride, although statistically rare, include sexual dysfunction, breast tenderness and depression.[7] Exposure during pregnancy is specifically contraindicated because dutasteride, being a form of antiandrogen, may interfere with the sexual differentiation of the male foetus.[3][7]

Dutasteride was patented in 1993 by GlaxoSmithKline and was approved for medical use in 2001.[9][7] It is available as a generic medication.[4] In 2017, it was the 276th most commonly prescribed medication in the United States, with more than one million prescriptions.[10][11]

Medical uses[edit]

Enlarged prostate[edit]

Dutasteride is used for treating benign prostatic hyperplasia (BPH); colloquially known as an "enlarged prostate".[8][12] It is approved by the Food and Drug Administration (FDA) in the U.S. for this indication.[13]

Prostate cancer[edit]

A 2010 Cochrane review found a 25–26% reduction in the risk of developing prostate cancer with 5α-reductase inhibitor chemoprevention.[14] However, 5α-reductase inhibitors have been found to increase the risk of developing certain rare but aggressive forms of prostate cancer (27% risk increase), although not all studies have observed this.[15] There is insufficient data to determine if they have an effect on the overall risk of death from prostate cancer.[15]

Scalp hair loss[edit]

Dutasteride is approved for the treatment of male androgenetic alopecia in South Korea and Japan at a dosage of 0.5 mg per day.[5][16] It has been found in several studies to induce hair regrowth in men more rapidly and to a greater extent than even the highest approved dosage of finasteride.[5][17][18][19] The superior effectiveness of dutasteride relative to finasteride for this indication is related to the fact that the inhibition of 5α-reductase and consequent reduction of 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.[20][21]

Excessive hair growth[edit]

Although no reports specific to dutasteride currently exist,[22][3] 5α-reductase inhibitors like finasteride have been found to be effective in the treatment of hirsutism (excessive facial and/or body hair growth) in women.[3] In a study of 89 women with hyperandrogenism due to persistent adrenarche syndrome, finasteride produced a 93% reduction in facial hirsutism and a 73% reduction in bodily hirsutism after 2 years of treatment.[3] Other studies using finasteride for hirsutism have also found it to be clearly effective.[3] Dutasteride may be more effective than finasteride for this indication due to the fact that its inhibition of the 5α-reductase enzyme is comparatively more complete.[1]

Transgender hormone therapy[edit]

Dutasteride is sometimes used as a component of hormone therapy for transgender women in combination with an estrogen and/or another antiandrogen like spironolactone.[6] It may be useful for treating scalp hair loss or in those who have issues tolerating spironolactone.[6]

Available forms[edit]

Dutasteride is provided in the form of soft oil-filled gelatin oral capsules containing 0.5 mg dutasteride each.[23]

Contraindications[edit]

Women who are or who may become pregnant should not handle the drug. Dutasteride can cause birth defects, specifically ambiguous genitalia and undermasculinization, in male fetuses.[23][24] This is due to its antiandrogenic effects and is seen naturally in 5α-reductase deficiency.[24] As such, women who are pregnant should never take dutasteride.[23] People taking dutasteride should not donate blood to prevent birth defects if a pregnant woman receives blood and, due to its long elimination half-life, should also not donate blood for at least 6 months after the cessation of treatment.[23]

Children and people with known significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride should not take dutasteride.[23]

Adverse effects[edit]

Dutasteride has overall been found to be well tolerated in studies of both men and women, producing minimal side effects.[15] Adverse effects include headache and gastrointestinal discomfort.[15] Isolated reports of menstrual changes, acne, and dizziness also exist.[15] There is a small risk of gynecomastia (breast development or enlargement) in men.[15] The risk of gynecomastia with 5α-reductase inhibitors is about 2.8%.[25]

The FDA has added a warning to dutasteride about an increased risk of high-grade prostate cancer.[26] While the potential for positive, negative or neutral changes to the potential risk of developing prostate cancer with dutasteride has not been established, evidence has suggested it may temporarily reduce the growth and prevalence of benign prostate tumors, but could also mask the early detection of prostate cancer. The primary area for concern is for patients who may develop prostate cancer whilst taking dutasteride for benign prostatic hyperplasia, which in turn could delay diagnosis and early treatment of the prostate cancer, thereby potentially increasing the risk of these patients developing high-grade prostate cancer.[27] A 2018 meta-analysis found no higher risk of breast cancer with 5α-reductase inhibitors.[28]

Sexual dysfunction, such as erectile dysfunction, loss of libido, or reduced semen volume are believed by many to be side effects of 5α-reductase inhibitors, occurring in as many as 4.8% of all patients, which in some cases may persist after discontinuing medication, leading to a lower quality of life. However as of 2021 this remains a highly contested topic in the academic literature, and metareview articles from credible international sources differ on whether this phenomenon is proven, whether it is a purely placebo/nocebo effect, or whether there is not enough evidence to reach a conclusion.[29][30][15][31][32][33] The Post-Finasteride Syndrome Foundation was created with a medical advisory board to study the topic (Finasteride being a similar 5α-reductase inhibitor),[34] and lawsuits allegeding harm from the drug are ongoing.[35]

Several small studies have reported an association between 5α-reductase inhibitors and depression.[15] However, most studies have not observed this side effect.[15] There have also been reports in a subset of men of long-lasting depression persisting even after discontinuation of dutasteride, although there is no scientific evidence to support such a claim.[33]

Overdose[edit]

There is no specific antidote for overdose of dutasteride as Dutasteride is extremely safe and well tolerated. Research studies show that Dutasteride is not lethal despite taking 100 times the normal dose.[36] Treatment of dutasteride overdose should be based on symptoms and should be supportive.[36] The long elimination half-life of dutasteride should be taken into consideration in the event of an overdose of the medication.[36] 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, respectively.[36]

Interactions[edit]

Despite any conclusive research studies, it is thought that 5α-reductase inhibitors like dutasteride may prevent the formation of neurosteroid metabolites like allopregnanolone from progesterone and hence may mitigate the psycho-cognitive effects of progesterone, particularly if it is administered orally.[37][38][39][40][41]

Pharmacology[edit]

Pharmacodynamics[edit]

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.[42] It inhibits all three forms of 5α-reductase, and can decrease DHT levels in the blood by up to 98%.[1][43][44] Specifically it is a competitive, mechanism-based (irreversible) inhibitor of all three isoforms of 5α-reductase, types I, II, and III (IC50 values are 3.9 nM for type I and 1.8 nM for type II).[1][43][45][46] This is in contrast to finasteride, which is similarly an irreversible inhibitor of 5α-reductase[46][47] but only inhibits the type II and III isoenzymes.[43] 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%.[44][2][42][48] 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,[48] where the type II isoform of 5α-reductase predominates.[45]

Since 5α-reductases degrade testosterone to DHT, the inhibition of them could cause an increase in testosterone. However, a 2018 review found that initiation of 5α-reductase inhibitors did not result in a consistent increase in testosterone levels, with some studies showing increases and others showing no change.[49] There was no statistically significant change in testosterone levels from 5α-reductase inhibitors in the overall meta-analysis, though men with lower baseline testosterone levels may show a rise in testosterone levels.

In addition to inhibition of DHT production, 5α-reductase inhibitors like dutasteride are also neurosteroidogenesis inhibitors, preventing the 5α-reductase-mediated biosynthesis of various neurosteroids including allopregnanolone (from progesterone), THDOC (from deoxycorticosterone), and 3α-androstanediol (from testosterone).[50] These neurosteroids are potent positive allosteric modulators of the GABAA receptor and have been found to possess antidepressant, anxiolytic, and pro-sexual effects in animal research.[50][51][52] For this reason, prevention of neurosteroid formation may be involved in the sexual dysfunction and depression that has been associated with 5α-reductase inhibitors like dutasteride.[50]

Pharmacokinetics[edit]

The oral bioavailability of dutasteride is approximately 60%.[1] Food does not adversely affect the absorption of dutasteride.[1] Peak plasma levels occur 2 to 3 hours after administration.[1] Levels of dutasteride in semen have been found to be 3 ng/mL, with no significant effects on DHT levels in sexual partners.[1] The drug is extensively metabolized in the liver by CYP3A4.[1] It has three major metabolites, including 6'-hydroxydutasteride, 4'-hydroxydutasteride, and 1,2-dihydrodutasteride; the former two are formed by CYP3A4, while the latter is not.[1] All three metabolites are active; 6'-hydroxydutasteride has similar potency as a 5α-reductase inhibitor to dutasteride, while the other two are less potent.[1] Dutasteride has an extremely long terminal or elimination half-life of about 4 or 5 weeks.[2][3] The elimination half-life of dutasteride is increased in the elderly (170 hours for men age 20–49 years, 300 hours for men age >70 years).[1] No dosage adjustment is necessary in the elderly nor in renal impairment.[1] Because of its long elimination half-life, dutasteride requires 5 or 6 months to reach steady state concentrations.[45] It also remains in the body for a long time after discontinuation and can be detected for up to 4 to 6 months.[1][2] In contrast to dutasteride, finasteride has a short terminal half-life of only 5 to 8 hours.[3][1] Dutasteride is eliminated mainly in the feces (40%) as metabolites.[1] A small portion (5%) is eliminated unchanged in the urine.[1]

Chemistry[edit]

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.[53][54] It is an analogue of finasteride in which the tert-butyl amide moiety has been replaced with a 2,5-bis(trifluoromethyl)phenyl group.[54]

History[edit]

Dutasteride was patented in 1996[55] and was first described in the scientific literature in 1997.[56] It was approved by the FDA for the treatment of BPH in November 2001 and was introduced into the United States market the following year under the brand name Avodart.[56] Dutasteride has subsequently been introduced in many other countries, including throughout Europe and South America.[56] The patent protection of dutasteride expired in November 2015 and the drug has since become available in the United States in a variety of low-cost generic formulations.[55]

It was approved for the treatment of scalp hair loss in South Korea since 2009 and in Japan since 2015.[57] It has not been approved for this indication in the United States,[5][16] though it is often used off-label.[20]

Society and culture[edit]

Avodart (dutasteride) 500 µg soft capsules.

Generic names[edit]

Dutasteride is the generic name of the drug Avodart and has the exact same formula, composed of seven other molecular ingredients and its INN, USAN, BAN, and JAN.[58]

Brand names[edit]

Dutasteride is sold primarily under the brand name Avodart and, in combination with tamsulosin (see dutasteride/tamsulosin), under the brand names Combodart and Duodart.[58] It is also sold under a variety of generic brand names.[58] Dutasteride is also available in combination with alfuzosin under the brand names Alfusin-D and Dutalfa, but only in India.[58]

Availability[edit]

Dutasteride is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, many other European countries, Australia, and South Africa, as well as in Latin America, Asia, and elsewhere.[58] It is available as a generic medication in the United States and other countries.[55]

Research[edit]

Dutasteride has been studied in combination with bicalutamide in the treatment of prostate cancer.[59][60][61][62][63]

A study found that dutasteride, which blocks the formation of the neurosteroid allopregnanolone from progesterone, is effective in reducing symptoms in women with premenstrual dysphoric disorder.[37]

References[edit]

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Lemke TL, Williams DA (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1286–1287. ISBN 978-0-7817-6879-5.
  2. ^ a b c d Burchum J, Rosenthal L (2 December 2014). Lehne's Pharmacology for Nursing Care. Elsevier Health Sciences. pp. 803–. ISBN 978-0-323-34026-7.
  3. ^ a b c d e f g h Blume-Peytavi U, Whiting DA, Trüeb RM (26 June 2008). Hair Growth and Disorders. Springer Science & Business Media. pp. 182, 369. ISBN 978-3-540-46911-7.
  4. ^ a b c British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 769. ISBN 9780857113382.
  5. ^ a b c d Shapiro J, Otberg N (17 April 2015). Hair Loss and Restoration, Second Edition. CRC Press. pp. 39–. ISBN 978-1-4822-3199-1.
  6. ^ a b c Wesp LM, Deutsch MB (March 2017). "Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons". The Psychiatric Clinics of North America. 40 (1): 99–111. doi:10.1016/j.psc.2016.10.006. PMID 28159148.
  7. ^ a b c d "Dutasteride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 18 March 2019.
  8. ^ a b Wu C, Kapoor A (July 2013). "Dutasteride for the treatment of benign prostatic hyperplasia". Expert Opinion on Pharmacotherapy. 14 (10): 1399–408. doi:10.1517/14656566.2013.797965. PMID 23750593. S2CID 25041466.
  9. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 483. ISBN 9783527607495.
  10. ^ "The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
  11. ^ "Dutasteride - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
  12. ^ Slater S, Dumas C, Bubley G (March 2012). "Dutasteride for the treatment of prostate-related conditions". Expert Opinion on Drug Safety. 11 (2): 325–30. doi:10.1517/14740338.2012.658040. PMID 22316171. S2CID 207487490.
  13. ^ "Drugs@FDA: FDA Approved Drug Products". www.accessdata.fda.gov.
  14. ^ Wilt TJ, Macdonald R, Hagerty K, Schellhammer P, Tacklind J, Somerfield MR, Kramer BS (November 2010). "5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review". BJU International. 106 (10): 1444–51. doi:10.1111/j.1464-410X.2010.09714.x. PMID 20977593. S2CID 22178061.
  15. ^ a b c d e f g h i Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS (July 2016). "Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review". The Journal of Clinical and Aesthetic Dermatology. 9 (7): 56–62. PMC 5023004. PMID 27672412.
  16. ^ a b Choi GS, Kim JH, Oh SY, Park JM, Hong JS, Lee YS, Lee WS (August 2016). "Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in the Treatment of Androgenetic Alopecia". Annals of Dermatology. 28 (4): 444–50. doi:10.5021/ad.2016.28.4.444. PMC 4969473. PMID 27489426.
  17. ^ Dhurat, Rachita; Sharma, Aseem; Rudnicka, Lidia; Kroumpouzos, George; Kassir, Martin; Galadari, Hassan; Wollina, Uwe; Lotti, Torello; Golubovic, Masa; Binic, Iva; Grabbe, Stephan; Goldust, Mohamad (May 2020). "5‐Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms, current concepts, comparative efficacy, and safety". Dermatologic Therapy. 33 (3): e13379. doi:10.1111/dth.13379. PMID 32279398. S2CID 215748750.
  18. ^ Zhou Z, Song S, Gao Z, Wu J, Ma J, Cui Y (2019). "The efficacy and safety of dutasteride compared with finasteride in treating men with androgenetic alopecia: a systematic review and meta-analysis". Clinical Interventions in Aging. 14: 399–406. doi:10.2147/CIA.S192435. PMC 6388756. PMID 30863034.
  19. ^ Olsen, Elise A.; Hordinsky, Maria; Whiting, David; Stough, Dow; Hobbs, Stuart; Ellis, Melissa L.; Wilson, Timothy; Rittmaster, Roger S.; Dutasteride Alopecia Research, Team. (December 2006). "The importance of dual 5α-reductase inhibition in the treatment of male pattern hair loss: Results of a randomized placebo-controlled study of dutasteride versus finasteride". Journal of the American Academy of Dermatology. 55 (6): 1014–1023. doi:10.1016/j.jaad.2006.05.007. PMID 17110217.
  20. ^ a b Nusbaum AG, Rose PT, Nusbaum BP (August 2013). "Nonsurgical therapy for hair loss". Facial Plastic Surgery Clinics of North America. 21 (3): 335–42. doi:10.1016/j.fsc.2013.04.003. PMID 24017975.
  21. ^ Carmina E, Azziz R, Bergfeld W, Escobar-Morreale HF, Futterweit W, Huddleston H, et al. (July 2019). "Female Pattern Hair Loss and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee". The Journal of Clinical Endocrinology and Metabolism. 104 (7): 2875–2891. doi:10.1210/jc.2018-02548. PMID 30785992.
  22. ^ Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I (19 September 2013). Treatment of Skin Disease: Comprehensive Therapeutic Strategies. Elsevier Health Sciences. pp. 327–. ISBN 978-0-7020-5236-1.
  23. ^ a b c d e "FDA prescribing information" (PDF). June 2011. Retrieved 15 September 2013.
  24. ^ a b McVary KT, Welliver C (12 August 2016). 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. Elsevier Health Sciences. pp. 396–. ISBN 978-0-323-45994-5.
  25. ^ Trost L, Saitz TR, Hellstrom WJ (May 2013). "Side Effects of 5-Alpha Reductase Inhibitors: A Comprehensive Review". Sexual Medicine Reviews. 1 (1): 24–41. doi:10.1002/smrj.3. PMID 27784557.
  26. ^ "FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer". U.S. Food and Drug Administration. 18 June 2019.
  27. ^ Walsh PC (April 2010). "Chemoprevention of prostate cancer". The New England Journal of Medicine. 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
  28. ^ Wang J, Zhao S, Luo L, Li E, Li X, Zhao Z (2018). "5-alpha Reductase Inhibitors and risk of male breast cancer: a systematic review and meta-analysis". International Braz J Urol. 44 (5): 865–873. doi:10.1590/S1677-5538.IBJU.2017.0531. PMC 6237523. PMID 29697934.
  29. ^ Traish, Abdulmaged M. (January 2020). "Post-finasteride syndrome: a surmountable challenge for clinicians". Fertility and Sterility. 113 (1): 21–50. doi:10.1016/j.fertnstert.2019.11.030. PMID 32033719. S2CID 211064052.
  30. ^ Fertig, Raymond; Shapiro, Jerry; Bergfeld, Wilma; Tosti, Antonella (2017). "Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome". Skin Appendage Disorders. 2 (3–4): 120–129. doi:10.1159/000450617. PMC 5264352. PMID 28232919.
  31. ^ Liu L, Zhao S, Li F, Li E, Kang R, Luo L, et al. (September 2016). "Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials". The Journal of Sexual Medicine. 13 (9): 1297–1310. doi:10.1016/j.jsxm.2016.07.006. PMID 27475241.
  32. ^ POP, ANCA; KISS, BELA; LOGHIN, FELICIA (2013). "Endocrine disrupting effects of butylated hydroxyanisole (BHA - E320)". Clujul Medical. 86 (1): 16–20. PMC 4462476. PMID 26527908.
  33. ^ a b Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML (March 2011). "Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients". The Journal of Sexual Medicine. 8 (3): 872–84. doi:10.1111/j.1743-6109.2010.02157.x. PMID 21176115.
  34. ^ "The Post-Finasteride Syndrome Foundation – Dedicated to supporting research and finding treatments for PFS patients worldwide". Retrieved 2021-12-24.
  35. ^ Pierson, Brendan (2021-09-08). "Group sues to have hair-loss drug Propecia pulled from market". Reuters. Retrieved 2021-12-24.
  36. ^ a b c d "Prescribing information" (PDF). www.accessdata.fda.gov. Retrieved 2020-01-10.
  37. ^ a b Pearlstein T (April 2016). "Treatment of Premenstrual Dysphoric Disorder: Therapeutic Challenges". Expert Review of Clinical Pharmacology. 9 (4): 493–496. doi:10.1586/17512433.2016.1142371. PMID 26766596. 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
  38. ^ Goletiani NV, Keith DR, Gorsky SJ (October 2007). "Progesterone: review of safety for clinical studies". Experimental and Clinical Psychopharmacology. 15 (5): 427–44. doi:10.1037/1064-1297.15.5.427. PMID 17924777.
  39. ^ Wang-Cheng R, Neuner JM, Barnabei VM (2007). Menopause. ACP Press. p. 97. ISBN 978-1-930513-83-9.
  40. ^ Bergemann N, Ariecher-Rössler A (27 December 2005). Estrogen Effects in Psychiatric Disorders. Springer Science & Business Media. p. 179. ISBN 978-3-211-27063-9.
  41. ^ Bäckström T, Bixo M, Johansson M, Nyberg S, Ossewaarde L, Ragagnin G, et al. (February 2014). "Allopregnanolone and mood disorders". Progress in Neurobiology. 113: 88–94. doi:10.1016/j.pneurobio.2013.07.005. PMID 23978486. S2CID 207407084.
  42. ^ a b Bostwick DG, Cheng L (24 January 2014). Urologic Surgical Pathology. Elsevier Health Sciences. pp. 492–. ISBN 978-0-323-08619-6.
  43. ^ a b c Yamana K, Labrie F, Luu-The V (August 2010). "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". Hormone Molecular Biology and Clinical Investigation. 2 (3): 293–9. doi:10.1515/hmbci.2010.035. PMID 25961201. S2CID 28841145.
  44. ^ a b Bradbury R (30 January 2007). Cancer. Springer Science & Business Media. pp. 49–. ISBN 978-3-540-33120-9.
  45. ^ a b c Keam SJ, Scott LJ (2008). "Dutasteride: a review of its use in the management of prostate disorders". Drugs. 68 (4): 463–85. doi:10.2165/00003495-200868040-00008. PMID 18318566.
  46. ^ a b Gisleskog PO, Hermann D, Hammarlund-Udenaes M, Karlsson MO (December 1998). "A model for the turnover of dihydrotestosterone in the presence of the irreversible 5 alpha-reductase inhibitors GI198745 and finasteride". Clinical Pharmacology and Therapeutics. 64 (6): 636–47. doi:10.1016/S0009-9236(98)90054-6. PMID 9871428. S2CID 42901328.
  47. ^ Keserü G, Swinney DC (28 July 2015). Thermodynamics and Kinetics of Drug Binding. Wiley. pp. 165–. ISBN 978-3-527-67304-9.
  48. ^ a b Heesakkers J, Chapple C, De Ridder D, Farag F (24 February 2016). Practical Functional Urology. Springer. pp. 280–. ISBN 978-3-319-25430-2.
  49. ^ Traish AM, Krakowsky Y, Doros G, Morgentaler A (January 2019). "Do 5α-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results". Sexual Medicine Reviews. 7 (1): 95–114. doi:10.1016/j.sxmr.2018.06.002. PMID 30098986.
  50. ^ a b c Traish AM, Mulgaonkar A, Giordano N (June 2014). "The dark side of 5α-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression". Korean Journal of Urology. 55 (6): 367–79. doi:10.4111/kju.2014.55.6.367. PMC 4064044. PMID 24955220.
  51. ^ Weizman A (1 February 2008). Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment. Springer Science & Business Media. ISBN 978-1-4020-6854-6.
  52. ^ Tvrdeić A, Poljak L (2016). "Neurosteroids, GABAA receptors and neurosteroid based drugs: are we witnessing the dawn of the new psychiatric drugs?". Endocrine Oncology and Metabolism. 2 (1): 60–71. doi:10.21040/eom/2016.2.7.
  53. ^ Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1381–. ISBN 978-1-60913-345-0.
  54. ^ a b Enrique Ravina (11 January 2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. pp. 183–. ISBN 978-3-527-32669-3.
  55. ^ a b c "Generic Avodart Availability". Drugs.com.
  56. ^ a b c Llewellyn W (2011). Anabolics. Molecular Nutrition Llc. pp. 968–, 971–. ISBN 978-0-9828280-1-4.
  57. ^ MacDonald G. "GSK Japan delays alopecia drug launch after Catalent manufacturing halt".
  58. ^ a b c d e "Dutasteride". Drugs.com.
  59. ^ Merrick GS, Butler WM, Wallner KE, Galbreath RW, Allen ZA, Kurko B (July 2006). "Efficacy of neoadjuvant bicalutamide and dutasteride as a cytoreductive regimen before prostate brachytherapy". Urology. 68 (1): 116–20. doi:10.1016/j.urology.2006.01.061. PMID 16844453.
  60. ^ Sartor O, Gomella LG, Gagnier P, Melich K, Dann R (October 2009). "Dutasteride and bicalutamide in patients with hormone-refractory prostate cancer: the Therapy Assessed by Rising PSA (TARP) study rationale and design". The Canadian Journal of Urology. 16 (5): 4806–12. PMID 19796455.
  61. ^ Chu FM, Sartor O, Gomella L, Rudo T, Somerville MC, Hereghty B, Manyak MJ (August 2015). "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". European Journal of Cancer. 51 (12): 1555–69. doi:10.1016/j.ejca.2015.04.028. PMID 26048455.
  62. ^ Gaudet M, Vigneault É, Foster W, Meyer F, Martin AG (January 2016). "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". Radiotherapy and Oncology. 118 (1): 141–7. doi:10.1016/j.radonc.2015.11.022. PMID 26702991.
  63. ^ Dijkstra S, Witjes WP, Roos EP, Vijverberg PL, Geboers AD, Bruins JL, et al. (2016). "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". SpringerPlus. 5: 653. doi:10.1186/s40064-016-2280-8. PMC 4870485. PMID 27330919.

Further reading[edit]

  • Frye SV (2006). "Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor". Current Topics in Medicinal Chemistry. 6 (5): 405–21. doi:10.2174/156802606776743101. PMID 16719800.

External links[edit]

  • "Dutasteride". Drug Information Portal. U.S. National Library of Medicine.