Finasteride – Wikipedia

Finasteride - Wikipedia
Finasteride
Finasteride.svg
Finasteride-3D-balls.png
Scientific knowledge
Commerce names Proscar, Propecia, Finide, others
Different names MK-906; YM-152; L-652,931; 17β-(N-tert-Butylcarbamoyl)-4-aza-5α-androst-1-en-3-one; N-(1,1-Dimethylethyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide
AHFS/Medicine.com Monograph
MedlinePlus a698016
License knowledge
Being pregnant
class
  • AU: X (Excessive threat)
  • US: X (Contraindicated)
Routes of
administration
By mouth
Drug class 5α-Reductase inhibitor
ATC code
Authorized standing
Authorized standing
Pharmacokinetic knowledge
Bioavailability 65%[5]
Protein binding 90%[5]
Metabolism Liver (CYP3A4, ALDH)[5]
Elimination half-life Adults: 5–6 hours[5]
Aged: >Eight hours[5]
Excretion Feces: 57%[5]
Urine: 40%[5]
Identifiers
CAS Quantity
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.149.445 Edit this at Wikidata
Chemical and bodily knowledge
System C23H36N2O2
Molar mass 372.553 g·mol−1
3D mannequin (JSmol)
  (confirm)

Finasteride, offered below the model names Proscar and Propecia amongst others, is a medicine used to deal with an enlarged prostate or hair loss in males.[6] It can be used to deal with extreme hair development in girls and as part of hormone remedy for transgender girls.[7][8] It’s taken by mouth.[6]

Finasteride is a 5α-reductase inhibitor and subsequently an antiandrogen.[9] It really works by reducing the manufacturing of dihydrotestosterone (DHT) by about 70%, together with within the prostate gland and the scalp.[6]

Unintended effects from finasteride are uncommon,[10] nonetheless some males expertise sexual dysfunction, melancholy, and breast enlargement.[11][12] In some males, sexual dysfunction might persist after stopping the remedy.[13][14] It could additionally cover the early signs of sure types of prostate most cancers.[12]

Finasteride was patented in 1984 and permitted for medical use in 1992.[15] It’s out there as a generic remedy.[16] In 2017, it was the 86th-most generally prescribed remedy in the USA, with greater than 9 million prescriptions.[17][18]

Medical makes use of[edit]

Finasteride is indicated for the therapy of symptomatic benign prostatic hyperplasia (BPH) in males with an enlarged prostate [3] and for the therapy of male sample hair loss (androgenetic alopecia) in males.[4]

Enlarged prostate[edit]

Physicians generally prescribe finasteride for the therapy of benign prostatic hyperplasia (BPH), informally referred to as an enlarged prostate.[19] Finasteride might enhance the signs related to BPH comparable to problem urinating, getting up in the course of the evening to urinate, hesitation in the beginning and finish of urination, and decreased urinary circulate.[20] It offers much less symptomatic reduction than alpha-1 blockers comparable to tamsulosin and symptomatic reduction is slower in onset (six months or extra of therapy with finasteride could also be required to find out the therapeutic outcomes of therapy).[medical citation needed] Symptomatic advantages are primarily seen in these with prostate quantity > 40 cm3.[medical citation needed] In long-term research finasteride however not alpha-1 inhibitors scale back the chance of acute urinary retention (−57% at Four years) and the necessity for surgical procedure (−54% at Four years).[medical citation needed] If the drug is discontinued, any therapeutic advantages are reversed inside about 6–Eight months.[3][10]

Scalp hair loss[edit]

Finasteride can be used to deal with male sample baldness (androgenic alopecia) in males, a situation that develops in as much as 80% of Caucasian males.[21][4] In the USA, finasteride and minoxidil are the one two FDA permitted medication for the therapy of male sample hair loss as of 2017.[22] Therapy with finasteride slows additional hair loss[23] and offers about 30% enchancment in hair loss after six months of therapy, with effectiveness persisting so long as the drug is taken.[12] Taking finasteride results in a discount in scalp and serum DHT ranges; by reducing scalp ranges of DHT, finasteride can keep or improve the quantity of terminal hairs within the anagen part by inhibiting and generally reversing miniaturization of the hair follicle. Finasteride is simplest on the crown however can scale back hair loss in all areas of the scalp.[24][25] Finasteride has additionally been examined for sample hair loss in girls; nonetheless, the outcomes have been no higher than placebo.[26]

Prostate most cancers[edit]

In males over 55 years previous finasteride decreases the chance of low grade prostate most cancers however might improve the chance of excessive grade prostate most cancers and has no impact on total survival.[27]

A 2010 evaluation discovered a 25% discount within the threat of prostate most cancers with 5α-reductase inhibitor.[28] A follow-up research of the Medicare claims of members in a 10-year Prostate Most cancers Prevention Trial suggests the discount in prostate most cancers is maintained even after discontinuation of therapy.[29] Nonetheless, 5α-reductase inhibitors have been discovered to extend the chance of growing sure uncommon however aggressive types of prostate most cancers (27% threat improve), though not all research have noticed this.[30] No affect of 5-α-reductase inhibitor on survival has been present in folks with prostate most cancers.[30]

Extreme hair development[edit]

Finasteride has been discovered to be efficient within the therapy of hirsutism (extreme facial and/or physique hair development) in girls. In a research of 89 girls with hyperandrogenism on account of persistent adrenarche syndrome, finasteride produced a 93% discount in facial hirsutism and a 73% discount bodily hirsutism after 2 years of therapy. Different research utilizing finasteride for hirsutism have additionally discovered it to be clearly efficient.[7]

Transgender hormone remedy[edit]

Finasteride is usually utilized in hormone alternative remedy for transgender girls on account of its antiandrogenic results, together with a type of estrogen. Nonetheless, little scientific analysis of finasteride use for this goal has been carried out and proof of security or efficacy is restricted.[8] Furthermore, warning has been really helpful when prescribing finasteride to transgender girls, as finasteride could also be related to unwanted effects comparable to melancholy, anxiousness, and suicidal ideation, signs which can be notably prevalent within the transgender inhabitants and in others at excessive threat already.[31]

Opposed results[edit]

A 2010 Cochrane evaluation concluded that opposed results from finasteride are uncommon when used for BPH.[10] When finasteride was initially permitted for hair loss in 1997, the FDA reported that it appeared effectively tolerated, with the most typical unwanted effects being associated to sexual operate.[32] Finasteride is contraindicated in being pregnant.[33][34] The Meals and Drug Administration advises that donation of blood or plasma be deferred for a minimum of one month after taking the final dose of finasteride.[35]

The FDA has added a warning to 5α-reductase inhibitors regarding an elevated threat of high-grade prostate most cancers, because the therapy of BPH lowers PSA (prostate-specific antigen), which might masks the event of prostate most cancers.[36][37] Though total incidence of male breast most cancers in scientific trials for finasteride 5 mg was not elevated, there are post-marketing stories of breast most cancers in affiliation with its use, although out there proof doesn’t present readability as as to if there’s a causative relationship between finasteride and these cancers.[4][38] A 2018 meta-analysis discovered no greater threat of breast most cancers with 5α-reductase inhibitors.[39] Some males develop gynecomastia (breast improvement or enlargement) following finasteride utilization.[40][41][42][43] The chance of gynecomastia with 5α-reductase inhibitors is low at about 1.5%.[44] Depressive signs and suicidality have been reported.[45]

Sexual dysfunction[edit]

Finasteride causes short-term sexual dysfunction in some males, which can persist in some males after stopping the remedy.[13][14] There are case stories of persistent diminished libido or erectile dysfunction after stopping the drug and the FDA has up to date the label to tell folks of those stories.[12][46][44]

The 2010 Cochrane evaluation discovered that in contrast with placebo, males taking finasteride are at elevated threat for impotence, erectile dysfunction, decreased libido, and ejaculation dysfunction for the primary 12 months of therapy. The charges grew to become indistinguishable from placebo after 2–Four years and these unwanted effects normally bought higher over time.[10][47] A 2016 meta-analysis discovered that sexual dysfunction, together with erectile dysfunction, lack of libido, and diminished ejaculate, might happen in 3.Four to 15.8% of males handled with finasteride or dutasteride.[30] This opposed impact has been linked to decrease high quality of life and may trigger stress in relationships.[48]

Lengthy-term[edit]

Finasteride might trigger persistent opposed sexual, neurological and bodily results in a subset of males.[13][14] This has been known as post-finasteride syndrome, characterised by reported sexual and bodily signs comparable to lack of libidio, erectile dysfunction, ejaculatory problems, discount in penis measurement, penile curvature, diminished sensation, male breast enlargement, muscular atrophy, fatigue and severely dry pores and skin. Folks with post-finasteride syndrome might expertise melancholy and anxiousness, cognitive impairment and suicidal ideas.[14]

Publish-finasteride syndrome might also have diminished ranges of neurosteroids comparable to allopregnanolone of their cerebrospinal fluid. One research discovered that 1.4% developed persistent sexual dysfunction.[13]

A 2019 Reuters investigation confirmed that Merck discovered proof of persistent unwanted effects of their authentic scientific trials and didn’t disclose it of their warning label.[49][50] They uncovered court docket filings which demonstrated that Merck misrepresented Propecia’s security document following scientific trials within the mid-late 1990s.[49]

In a single deposition, Charlotte Merritt, who oversaw regulatory exercise for Propecia, acknowledged that Merck modified Propecia’s label for sexual opposed occasions in 2002, 4 years after Propecia hit the market. The label modified from “decision occurred in all males who discontinued remedy with Propecia ” to “decision occurred in males who discontinued remedy with Propecia”. Merritt testified that Merck eradicated the phrase “all” on account of proof from the scientific trials of opposed occasions that didn’t resolve following discontinuation of use.[50] In one other deposition, Paul Howes, the top of selling for Propecia acknowledged that Merck was conscious that warnings of sexual unwanted effects, notably persistent to everlasting unwanted effects, would have a devastating affect on gross sales.[50]

Overdose[edit]

Finasteride has been studied in people at single doses of as much as 400 mg and at steady dosages of as much as 80 mg/day for 3 months, with out opposed results noticed.[4][3][51][4][3] There is no such thing as a particular really helpful antidote for finasteride overdose.[4][3]

Interactions[edit]

No important drug interactions have been noticed between finasteride and a restricted number of drugs.[52]

Pharmacology[edit]

Pharmacodynamics[edit]

Finasteride is a 5α-reductase inhibitor.[4][5] It’s particularly a selective inhibitor of the kind II and III isoforms of the enzyme.[5][53][54] By inhibiting these two isozymes of 5α-reductase, finasteride reduces the formation of the potent androgen dihydrotestosterone (DHT) from its precursor testosterone in sure tissues within the physique such because the prostate gland, pores and skin, and hair follicles.[5][55] As such, finasteride is a kind of antiandrogen, or extra particularly, an androgen synthesis inhibitor.[56][57] Nonetheless, some authors don’t outline finasteride as an “antiandrogen,” a time period which might refer extra particularly to antagonists of the androgen receptor.[58]

Finasteride ends in a lower of circulating DHT ranges by about 65 to 70% with an oral dosage of 5 mg/day and of DHT ranges within the prostate gland by as much as 80 to 90% with an oral dosage of 1 or 5 mg/day.[53][59][60] In parallel, circulating ranges of testosterone improve by roughly 10%, whereas native concentrations of testosterone within the prostate gland improve by about 7-fold and native testosterone ranges in hair follicles improve by round 27 to 53%.[61][62] An oral dosage of finasteride of solely 0.2 mg/day has been discovered to realize near-maximal suppression of DHT ranges (68.6% for 0.2 mg/day relative to 72.2% for five mg/day).[62][63] Finasteride doesn’t fully suppress DHT manufacturing as a result of it lacks important inhibitory results on the 5α-reductase sort I isoenzyme, with greater than 100-fold much less inhibitory efficiency for sort I as in comparison with sort II (IC50 = 313 nM and 11 nM, respectively).[4][5] That is in distinction to inhibitors of all three isoenzymes of 5α-reductase like dutasteride, which might scale back DHT ranges in all the physique by greater than 99%.[53] Along with inhibiting 5α-reductase, finasteride has additionally been discovered to competitively inhibit 5β-reductase (AKR1D1).[64] Nonetheless, its affinity for the enzyme is considerably lower than for 5α-reductase (an order of magnitude lower than for 5α-reductase sort I) and therefore is unlikely to be of scientific significance.[64]

As of 2012, the tissues during which the totally different isozymes of 5α-reductase are expressed should not totally clear.[55] It’s because totally different investigators have obtained various outcomes with totally different reagents, strategies, and tissues examined.[55] Nonetheless, the totally different isozymes of 5α-reductase look like extensively expressed, with notable tissues together with the prostate gland, seminal vesicles, testes, epididymides, pores and skin, hair follicles, liver, kidneys, and mind, amongst others.[55]

By inhibiting 5α-reductase and thus stopping DHT manufacturing, finasteride reduces androgen signaling in tissues just like the prostate gland and the scalp. Within the prostate, this reduces prostate quantity, which improves BPH and reduces threat of prostate most cancers. Finasteride reduces prostate quantity by 20 to 30% in males with benign prostatic hyperplasia.[65] Inhibition of 5α-reductase additionally reduces epididymal weight, and reduces motility and regular morphology of spermatozoa within the epididymis.[66]

Neurosteroids like 3α-androstanediol (derived from DHT) and allopregnanolone (derived from progesterone) activate the GABAA receptor within the mind; as a result of finasteride prevents the formation of neurosteroids, it features as a neurosteroidogenesis inhibitor and should contribute to a discount of GABAA exercise. Discount of GABAA receptor activation by these neurosteroids has been implicated in melancholy, anxiousness, and sexual dysfunction.[67][68][69]

Pharmacokinetics[edit]

The imply oral bioavailability of finasteride is roughly 65%.[5] The absorption of finasteride just isn’t affected by meals.[4][3] At steady-state with 1 mg/day finasteride, imply peak concentrations of finasteride have been 9.2 ng/mL (25 nmol/L).[4] Conversely, following a single 5 mg dose of finasteride, imply peak ranges of finasteride have been 37 ng/mL (99 nmol/L), and plasma concentrations elevated by 47 to 54% following 2.5 weeks of continued day by day administration.[3] The amount of distribution of finasteride is 76 L.[5] Its plasma protein binding is 90%.[5] The drug has been discovered to cross the blood–mind barrier, whereas ranges in semen have been discovered to be undetectable.[5]

Finasteride is extensively metabolized within the liver, first by hydroxylation by way of CYP3A4 after which by aldehyde dehydrogenase.[5] It has two main metabolites, that are the tert-butyl facet chain monohydroxylated and monocarboxylic acid metabolites.[5] These metabolites present roughly 20% of the inhibitory exercise of finasteride on 5α-reductase.[5] Therefore, the metabolites of finasteride should not notably energetic.[5] The drug has a terminal half-life of 5 to six hours in grownup males (18–60 years of age) and a terminal half-life of 8 hours or extra in aged males (greater than 70 years of age).[5] It’s eradicated as its metabolites 57% within the feces and 40% within the urine.[5]

Chemistry[edit]

Finasteride, often known as 17β-(N-tert-butylcarbamoyl)-4-aza-5α-androst-1-en-3-one, is an artificial androstane steroid and 4-azasteroid.[52][70] It’s an analogue of androgen steroid hormones like testosterone and DHT.[52] As an unconjugated steroid, finasteride is a extremely lipophilic compound.[52][71]

Historical past[edit]

In 1942, James Hamilton noticed that prepubertal castration prevents the later improvement of male sample baldness in mature males.[72] In 1974, Julianne Imperato-McGinley of Cornell Medical Faculty in New York attended a convention on start defects. She reported on a bunch of intersex youngsters within the Caribbean who appeared sexually ambiguous at start, and have been initially raised as women, however then grew exterior male genitalia and different masculine attribute after onset of puberty. These youngsters, regardless of being raised as women till puberty, have been usually heterosexual, and have been termed “Guevedoces” by their area people, which implies “penis at twelve” in Spanish.[73] Her analysis group discovered these youngsters shared a genetic mutation, inflicting deficiency of the 5α-reductase enzyme and male hormone dihydrotestosterone (DHT), which was discovered to have been the etiology behind abnormalities in male sexual improvement. Upon maturation, these people have been noticed to have smaller prostates which have been underdeveloped, and have been additionally noticed to lack incidence of male sample baldness.[74][75]

In 1975, copies of Imperato-McGinley’s presentation have been seen by P. Roy Vagelos, who was then serving as Merck’s basic-research chief. He was intrigued by the notion that decreased ranges of DHT led to the event of smaller prostates. Dr. Vagelos then sought to create a drug which might mimic the situation present in these youngsters to deal with older males who have been affected by benign prostatic hyperplasia.[76]

Finasteride was developed by Merck below the code title MK-906.[52] A workforce led by chemist Gary Rasmusson and biologist Jerry Brooks developed potential 5α-reductase inhibitors primarily based on transition state inhibitors, utilizing an iterative technique of molecular design, testing, and redesign.[77] In 1992, finasteride (5 mg) was permitted by the U.S. Meals and Drug Administration (FDA) for therapy of BPH, which Merck marketed below the model title Proscar. Rasmusson and Brooks have been awarded IPO’s “Inventor of the 12 months” award in 1993 for his or her work on finasteride.[78] In 1997, Merck was profitable in acquiring FDA approval for a second indication of finasteride (1 mg) for therapy of male sample hair loss, which was marketed below the model title Propecia.[79] It was the primary 5α-reductase inhibitor to be launched and was adopted by dutasteride in 2001.[80] The primary research of finasteride within the therapy of hirsutism in girls was revealed in 1994.[81]

Society and tradition[edit]

Economics[edit]

A month provide in the UK prices the NHS about GB£0.89 per thirty days as of 2019.[82] In the USA, the wholesale price of this quantity is about US$2.34.[83]

Generic names[edit]

Finasteride is the generic title of the drug and its INN, USAN, BAN, and JAN, whereas finastéride is its DCF.[84][85][86][87] Additionally it is recognized by its former developmental code names MK-906, YM-152, and L-652,931.[84][85][86][87]

Model names[edit]

Finasteride is marketed primarily below the model names Propecia, for sample hair loss, and Proscar, for BPH, each of that are merchandise of Merck & Co.[87] There may be 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck’s patent on finasteride for the therapy of BPH expired in June 2006.[88] Merck was awarded a separate patent for the usage of finasteride to deal with sample hair loss and it expired in November 2013.[89] Finasteride can be marketed below quite a lot of different model names all through the world.[87]

Controversy[edit]

Males within the U.S. and Canada involved about persistent sexual unwanted effects “coined the phrase ‘post-finasteride syndrome’, which they are saying is characterised by sexual, neurological, hormonal and psychological unwanted effects that may persist in males who’ve taken finasteride for hair loss or an enlarged prostate”.[90] In 2016, Merck was a defendant in roughly 1,370 product legal responsibility lawsuits which had been filed by clients alleging they’ve skilled persistent sexual unwanted effects following cessation of therapy with finasteride.[91]

Athletics[edit]

From 2005 to 2009, the World Anti-Doping Company banned finasteride as a result of it was found that the drug could possibly be used to masks steroid abuse.[92] It was faraway from the checklist efficient January 1, 2009, after enhancements in testing strategies made the ban pointless.[93] Athletes who used finasteride and have been banned from worldwide competitors embody skeleton racer Zach Lund, bobsledder Sebastien Gattuso, footballer Romário, and ice hockey goaltender José Théodore.[93][94]

Miscellaneous[edit]

The U.S. Meals and Drug Administration advises that donation of blood or plasma be deferred for a minimum of one month after taking the final dose of finasteride.[95] The UK additionally has a one-month deferral interval.[96]

Harold Bornstein, the previous[97] private doctor of United States President Donald Trump, acknowledged in 2017 that Trump was taking finasteride to advertise hair development.[98][99]

Analysis[edit]

Preliminary analysis means that topical finasteride could also be efficient within the therapy of sample hair loss.[100][101] Topical finasteride, just like the oral preparation, reduces serum DHT.[101] Nonetheless, research have proven that the extent of the discount of serum DHT is much less with the topical software.[citation needed]

DHT could also be concerned in the reason for zits, and 5α-reductase inhibitors could be efficient within the therapy of the situation.[102][103] A small retrospective research reported that finasteride was efficient within the therapy of zits in girls with regular testosterone ranges.[104][103] A randomized managed trial discovered that finasteride was much less efficient than flutamide or an ethinylestradiol/cyproterone acetate contraception tablet within the therapy of zits in girls with excessive androgen ranges.[104]

Androgens and estrogens could also be concerned in the reason for hidradenitis suppurativa (zits inversa).[105][106] Two case sequence have reported that finasteride is efficient within the therapy of hidradenitis suppurativa in women and girls.[104]

Finasteride and different antiandrogens could be helpful within the therapy of obsessive–compulsive dysfunction, however extra analysis is required.[107]

References[edit]

  1. ^ “Propecia 1 mg Movie-Coated Tablets – Abstract of Product Traits (SmPC)”. (emc). 27 July 2020. Retrieved 29 September 2020.
  2. ^ “Proscar 5mg film-coated Tablets – Abstract of Product Traits (SmPC)”. (emc). 10 July 2020. Retrieved 29 September 2020.
  3. ^ a b c d e f g h “Proscar- finasteride pill, movie coated”. DailyMed. 15 November 2019. Retrieved 16 September 2020.
  4. ^ a b c d e f g h i j ok “Propecia- finasteride pill, movie coated”. DailyMed. 15 November 2019. Retrieved 16 September 2020.
  5. ^ a b c d e f g h i j ok l m n o p q r s t u Lemke TL, Williams DA (2008). Foye’s Rules of Medicinal Chemistry (sixth ed.). Lippincott Williams & Wilkins. pp. 1286–. ISBN 978-0-7817-6879-5.
  6. ^ a b c “Finasteride Monograph for Professionals”. Medicine.com. American Society of Well being-System Pharmacists. Retrieved 5 March 2019.
  7. ^ a b Blume-Peytavi U, Whiting DA, Trüeb RM (26 June 2008). Hair Progress and Issues. Springer Science & Enterprise Media. p. 369. ISBN 978-3-540-46911-7.
  8. ^ a b Knezevich EL, Viereck LK, Drincic AT (January 2012). “Medical administration of grownup transsexual individuals”. Pharmacotherapy. 32 (1): 54–66. doi:10.1002/PHAR.1006. PMID 22392828. S2CID 12853220.
  9. ^ Ferri, Fred F. (2014). Ferri’s Scientific Advisor 2015 E-Guide: 5 Books in 1. Elsevier Well being Sciences. p. 580. ISBN 9780323084307.
  10. ^ a b c d Tacklind J, Fink HA, Macdonald R, Rutks I, Wilt TJ (October 2010). “Finasteride for benign prostatic hyperplasia”. The Cochrane Database of Systematic Evaluations (10): CD006015. doi:10.1002/14651858.CD006015.pub3. PMID 20927745.
  11. ^ Zakhem GA, Goldberg JE, Motosko CC, Cohen BE, Ho RS (1 July 2019). “Sexual dysfunction in males taking systemic dermatologic remedy: A scientific evaluation”. J Am Acad Dermatol. 81 (1): 163–172. doi:10.1016/j.jaad.2019.03.043. PMID 30905792.
  12. ^ a b c d Varothai S, Bergfeld WF (July 2014). “Androgenetic alopecia: an evidence-based therapy replace”. American Journal of Scientific Dermatology. 15 (3): 217–30. doi:10.1007/s40257-014-0077-5. PMID 24848508. S2CID 31245042.
  13. ^ a b c d Zakhem, GA; Goldberg, JE; Motosko, CC; Cohen, BE; Ho, RS (July 2019). “Sexual dysfunction in males taking systemic dermatologic remedy: A scientific evaluation”. Journal of the American Academy of Dermatology. 81 (1): 163–172. doi:10.1016/j.jaad.2019.03.043. PMID 30905792. In research addressing reversibility, most of those sufferers have decision of sexual opposed results after discontinuation of finasteride, and lots of have enchancment of opposed results over time with continued finasteride use. Nonetheless, some research CAPSULE SUMMARY d Prescription drugs are a typical reason for sexual dysfunction. Doable sexual opposed results must be mentioned with males utilizing these drugs. d We recognized proof for sexual opposed results in sufferers taking 11 systemic dermatologic drugs. Stage 1 proof evaluating sexual dysfunction as a major final result was out there for finasteride.
  14. ^ a b c d Traish, AM (January 2020). “Publish-finasteride syndrome: a surmountable problem for clinicians”. Fertility and Sterility. 113 (1): 21–50. doi:10.1016/j.fertnstert.2019.11.030. PMID 32033719.
  15. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 483. ISBN 9783527607495.
  16. ^ Sataloff RT, Sclafani AP (30 November 2015). Sataloff’s Complete Textbook of Otolaryngology: Head & Neck Surgical procedure: Facial Plastic and Reconstructive Surgical procedure. JP Medical Ltd. pp. 400–. ISBN 978-93-5152-459-5.
  17. ^ “The Prime 300 of 2020”. ClinCalc. Retrieved 11 April 2020.
  18. ^ “Finasteride – Drug Utilization Statistics”. ClinCalc. Retrieved 11 April 2020.
  19. ^ Smith, Angela B; Carson, Culley C (2009). “Finasteride within the therapy of sufferers with benign prostatic hyperplasia: a evaluation”. Therapeutics and Scientific Threat Administration. 5: 535–545. ISSN 1176-6336. PMC 2710385. PMID 19707263.
  20. ^ “Benign prostate enlargement”. nhs.uk. 20 October 2017. Retrieved 20 October 2020.
  21. ^ Kanti V1, Messenger A2, Dobos G1, Reygagne P3, Finner A4, Blumeyer A5, Trakatelli M6, Tosti A7,8, Del Marmol V9, Piraccini BM10, Nast A11, Blume-Peytavi U1. Proof-based (S3) guideline for the therapy of androgenetic alopecia in girls and in males – brief model. J Eur Acad Dermatol Venereol. 2018 Jan;32(1):11-22. doi: 10.1111/jdv.14624. Epub 2017 Nov 27.
  22. ^ Adil A, Godwin M (July 2017). “The effectiveness of remedies for androgenetic alopecia: A scientific evaluation and meta-analysis”. Journal of the American Academy of Dermatology. 77 (1): 136–141.e5. doi:10.1016/j.jaad.2017.02.054. PMID 28396101. S2CID 46036459.
  23. ^ Habif TP (23 April 2015). Scientific Dermatology. Elsevier Well being Sciences. pp. 934–. ISBN 978-0-323-26607-9.
  24. ^ Yim E, Nole KL, Tosti A (December 2014). “5α-Reductase inhibitors in androgenetic alopecia”. Present Opinion in Endocrinology, Diabetes and Weight problems. 21 (6): 493–8. doi:10.1097/MED.0000000000000112. PMID 25268732. S2CID 30008068.
  25. ^ Gupta AK, Charrette A (April 2014). “The efficacy and security of 5α-reductase inhibitors in androgenetic alopecia: a community meta-analysis and benefit-risk evaluation of finasteride and dutasteride”. The Journal of Dermatological Therapy. 25 (2): 156–61. doi:10.3109/09546634.2013.813011. PMID 23768246. S2CID 24833568.
  26. ^ Levy LL, Emer JJ (August 2013). “Feminine sample alopecia: present views”. Worldwide Journal of Ladies’s Well being. 5: 541–56. doi:10.2147/IJWH.S49337. PMC 3769411. PMID 24039457.
  27. ^ “Finasteride for Prostate Most cancers Prevention”. Nationwide Most cancers Institute. 28 August 2013. Retrieved Eight February 2020.
  28. ^ Wilt TJ, Macdonald R, Hagerty Okay, Schellhammer P, Tacklind J, Somerfield MR, Kramer BS (2010). “5-α-Reductase inhibitors for prostate most cancers chemoprevention: an up to date Cochrane systematic evaluation”. BJU Int. 106 (10): 1444–51. doi:10.1111/j.1464-410X.2010.09714.x. PMID 20977593. S2CID 22178061.
  29. ^ Unger JM, Hershman DL, Until C, Tangen CM, Barlow WE, Ramsey SD, Goodman PJ, Thompson IM (March 2018). “Utilizing Medicare Claims to Study Lengthy-term Prostate Most cancers Threat of Finasteride within the Prostate Most cancers Prevention Trial”. Journal of the Nationwide Most cancers Institute. 110 (11): 1208–1215. doi:10.1093/jnci/djy035. PMC 6235685. PMID 29534197.
  30. ^ a b c Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS (2016). “Opposed Results and Security of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Assessment”. J Clin Aesthet Dermatol. 9 (7): 56–62. PMC 5023004. PMID 27672412.
  31. ^ Trüeb, Ralph M. (2017). “Discriminating in favour of or towards males with elevated threat of finasteride-related unwanted effects?”. Experimental Dermatology. 26 (6): 527–528. doi:10.1111/exd.13155. ISSN 0906-6705. PMID 27489125. S2CID 36236057. […] warning is really helpful whereas prescribing oral finasteride to male-to-female transsexuals, because the drug has been related to inducing melancholy, anxiousness and suicidal ideation, signs which can be notably frequent in sufferers with gender dysphoria, who’re already at a excessive threat.[9]
  32. ^ FDA. “Abstract of Key Security Findings” (PDF). p. 98.
  33. ^ “PROPECIA Prescribing Data” (PDF). US Meals & Drug Administration / Merck & Co., Inc. Retrieved 30 January 2020.
  34. ^ “PROSCAR Prescribing Data” (PDF). US Meals & Drug Administration / Merck & Co., Inc. Retrieved 30 January 2020.
  35. ^ “Deferral of Blood and Plasma donors – Drugs”. FDA. 28 July 1993. Retrieved 30 January 2020.
  36. ^ FDA. Posted 9 June 2011. 5-alpha reductase inhibitors (5-ARIs): Label Change – Elevated Threat of Prostate Most cancers
  37. ^ Walsh PC (April 2010). “Chemoprevention of prostate most cancers”. The New England Journal of Drugs. 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
  38. ^ Medicines and Healthcare merchandise Regulatory Company Drug Security Replace. December 2009 Finasteride: potential threat of male breast most cancers
  39. ^ Wang J, Zhao S, Luo L, Li E, Li X, Zhao Z (2018). “5-alpha Reductase Inhibitors and threat of male breast most cancers: a scientific evaluation and meta-analysis”. Int Braz J Urol. 44 (5): 865–873. doi:10.1590/S1677-5538.IBJU.2017.0531. PMC 6237523. PMID 29697934.
  40. ^ Narula HS, Carlson HE (August 2014). “Gynaecomastia-pathophysiology, prognosis and therapy”. Nat Rev Endocrinol. 10 (11): 684–698. doi:10.1038/nrendo.2014.139. PMID 25112235. S2CID 40159424.
  41. ^ Deepinder F, Braunstein GD (2012). “Drug-induced gynecomastia: an evidence-based evaluation”. Knowledgeable Opinion on Drug Security. 11 (5): 779–795. doi:10.1517/14740338.2012.712109. PMID 22862307. S2CID 22938364.
  42. ^ Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF (April 2014). “Aldosterone antagonists for stopping the development of continual kidney illness”. Cochrane Database of Systematic Evaluations. 4 (4): CD007004. doi:10.1002/14651858.CD007004.pub3. PMID 24782282.
  43. ^ Aiman U, Haseeen MA, Rahman SZ (December 2009). “Gynecomastia: An ADR on account of drug interplay”. Indian Journal of Pharmacology. 41 (6): 286–7. doi:10.4103/0253-7613.59929. PMC 2846505. PMID 20407562.
  44. ^ a b Trost L, Saitz TR, Hellstrom WJ (2013). “Facet Results of 5-Alpha Reductase Inhibitors: A Complete Assessment”. Intercourse Med Rev. 1 (1): 24–41. doi:10.1002/smrj.3. PMID 27784557.
  45. ^ Locci A, Pinna G (2017). “Neurosteroid biosynthesis downregulation and adjustments in GABAA receptor subunit composition: A biomarker axis in stress-induced cognitive and emotional impairment”. Br. J. Pharmacol. 174 (19): 3226–3241. doi:10.1111/bph.13843. PMC 5595768. PMID 28456011.
  46. ^ FDA (11 April 2012). “Questions and Solutions: Finasteride Label Modifications”. US FDA. Retrieved 26 October 2014.
  47. ^ Mella JM, Perret MC, Manzotti M, Catalano HN, Guyatt G (October 2010). “Efficacy and security of finasteride remedy for androgenetic alopecia: a scientific evaluation”. Archives of Dermatology. 146 (10): 1141–50. doi:10.1001/archdermatol.2010.256. PMID 20956649.
  48. ^ Gur S, Kadowitz PJ, Hellstrom WJ (January 2013). “Results of 5-alpha reductase inhibitors on erectile operate, sexual need and ejaculation”. Knowledgeable Opinion on Drug Security. 12 (1): 81–90. doi:10.1517/14740338.2013.742885. PMID 23173718. S2CID 11624116.
  49. ^ a b “U.S. court docket let Merck cover secrets and techniques about standard drug’s dangers”. Reuters. Retrieved 17 February 2020.
  50. ^ a b c “In re: Propecia (Finasteride) Merchandise” (PDF). Retrieved 17 February 2020.
  51. ^ Frye SV (2006). “Discovery and scientific improvement of dutasteride, a potent twin 5alpha-reductase inhibitor”. Curr Prime Med Chem. 6 (5): 405–21. doi:10.2174/156802606776743101. PMID 16719800.
  52. ^ a b c d e Sudduth SL, Koronkowski MJ (1993). “Finasteride: the primary 5α-reductase inhibitor”. Pharmacotherapy. 13 (4): 309–25, dialogue 325–9. doi:10.1002/j.1875-9114.1993.tb02739.x (inactive Eight October 2020). PMID 7689728.CS1 maint: DOI inactive as of October 2020 (hyperlink)
  53. ^ a b c Yamana Okay, Labrie F, Luu-The V (August 2010). “Human sort Three 5α-reductase is expressed in peripheral tissues at greater ranges than varieties 1 and a pair of and its exercise is potently inhibited by finasteride and dutasteride”. Hormone Molecular Biology and Scientific Investigation. 2 (3): 293–9. doi:10.1515/hmbci.2010.035. PMID 25961201. S2CID 28841145.
  54. ^ Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M (February 2010). “An summary on 5alpha-reductase inhibitors”. Steroids. 75 (2): 109–53. doi:10.1016/j.steroids.2009.10.005. PMID 19879888. S2CID 44363501.
  55. ^ a b c d Azzouni F, Godoy A, Li Y, Mohler J (2012). “The 5 alpha-reductase isozyme household: a evaluation of fundamental biology and their function in human ailments”. Adv Urol. 2012: 1–18. doi:10.1155/2012/530121. PMC 3253436. PMID 22235201.
  56. ^ Victor R. Preedy (2012). Handbook of Hair in Well being and Illness. Springer Science & Enterprise Media. pp. 89–. ISBN 978-90-8686-728-8.
  57. ^ Jashin J. Wu (18 October 2012). Complete Dermatologic Drug Remedy E-Guide. Elsevier Well being Sciences. pp. 361–. ISBN 978-1-4557-3801-4.
  58. ^ Clapauch, Ruth; Weiss, Rita Vasconcellos; Rech, Ciciliana Maila Zilio (2017). “Testosterone and Ladies”. Testosterone. pp. 319–351. doi:10.1007/978-3-319-46086-4_17. ISBN 978-3-319-46084-0. Finasteride just isn’t really an antiandrogen however a 5α-reductase inhibitor.
  59. ^ Bartsch G, Rittmaster RS, Klocker H (April 2000). “Dihydrotestosterone and the idea of 5alpha-reductase inhibition in human benign prostatic hyperplasia”. European Urology. 37 (4): 367–80. doi:10.1159/000020181. PMID 10765065. S2CID 25793400.
  60. ^ Kim EH, Brockman JA, Andriole GL (January 2018). “The usage of 5-alpha reductase inhibitors within the therapy of benign prostatic hyperplasia”. Asian Journal of Urology. 5 (1): 28–32. doi:10.1016/j.ajur.2017.11.005. PMC 5780290. PMID 29379733.
  61. ^ Rittmaster RS (January 1994). “Finasteride”. N. Engl. J. Med. 330 (2): 120–5. doi:10.1056/NEJM199401133300208. PMID 7505051.
  62. ^ a b Libecco JF, Bergfeld WF (April 2004). “Finasteride within the therapy of alopecia”. Knowledgeable Opin Pharmacother. 5 (4): 933–40. doi:10.1517/14656566.5.4.933. PMID 15102575. S2CID 24296644.
  63. ^ Shapiro J, Kaufman KD (June 2003). “Use of finasteride within the therapy of males with androgenetic alopecia (male sample hair loss)”. J. Investig. Dermatol. Symp. Proc. 8 (1): 20–3. doi:10.1046/j.1523-1747.2003.12167.x. PMID 12894990.
  64. ^ a b Drury JE, Di Costanzo L, Penning TM, Christianson DW (July 2009). “Inhibition of human steroid 5beta-reductase (AKR1D1) by finasteride and construction of the enzyme-inhibitor complicated”. The Journal of Organic Chemistry. 284 (30): 19786–90. doi:10.1074/jbc.C109.016931. PMC 2740403. PMID 19515843.
  65. ^ Bostwick DG, Cheng L (24 January 2014). Urologic Surgical Pathology E-Guide. Elsevier Well being Sciences. pp. 402–. ISBN 978-0-323-08619-6.
  66. ^ Robaire B, Henderson NA (Could 2006). “Actions of 5alpha-reductase inhibitors on the epididymis”. Molecular and Mobile Endocrinology. 250 (1–2): 190–5. doi:10.1016/j.mce.2005.12.044. PMID 16476520. S2CID 53464391.
  67. ^ Finn DA, Beadles-Bohling AS, Beckley EH, Ford MM, Gililland KR, Gorin-Meyer RE, Wiren KM (2006). “A brand new take a look at the 5alpha-reductase inhibitor finasteride”. CNS Drug Evaluations. 12 (1): 53–76. doi:10.1111/j.1527-3458.2006.00053.x. PMC 6741762. PMID 16834758.
  68. ^ Römer B, Gass P (December 2010). “Finasteride-induced melancholy: new insights into doable pathomechanisms”. Journal of Beauty Dermatology. 9 (4): 331–2. doi:10.1111/j.1473-2165.2010.00533.x. PMID 21122055. S2CID 24328589.
  69. ^ Gunn BG, Brown AR, Lambert JJ, Belelli D (2011). “Neurosteroids and GABA(A) Receptor Interactions: A Deal with Stress”. Frontiers in Neuroscience. 5: 131. doi:10.3389/fnins.2011.00131. PMC 3230140. PMID 22164129.
  70. ^ Tian G, Stuart JD, Moss ML, Domanico PL, Bramson HN, Patel IR, Kadwell SH, Overton LK, Kost TA, Mook RA (1994). “17 beta-(N-tert-butylcarbamoyl)-4-aza-5 alpha-androstan-1-en-3-one is an energetic site-directed gradual time-dependent inhibitor of human steroid 5 alpha-reductase 1”. Biochemistry. 33 (8): 2291–6. doi:10.1021/bi00174a041. PMID 8117686.
  71. ^ Azeem A, Khan ZI, Aqil M, Ahmad FJ, Khar RK, Talegaonkar S (Could 2009). “Microemulsions as a surrogate provider for dermal drug supply”. Drug Improvement and Industrial Pharmacy. 35 (5): 525–47. doi:10.1080/03639040802448646. PMID 19016057. S2CID 205563538.
  72. ^ Hamilton, J (1942). “Male hormone stimulation is prerequisite and an incitant in frequent baldness”. American Journal of Anatomy. 71 (3): 451–480. doi:10.1002/aja.1000710306.
  73. ^ “The extraordinary case of the Guevedoces”. BBC Information. 20 September 2015. Retrieved Three September 2018.
  74. ^ Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (December 1974). “Steroid 5alpha-reductase deficiency in man: an inherited type of male pseudohermaphroditism”. Science. 186 (4170): 1213–5. Bibcode:1974Sci…186.1213I. doi:10.1126/science.186.4170.1213. PMID 4432067. S2CID 36427689.
  75. ^ Isfort AH, Emerick JE, Paz RA (11 November 2016). “5-Alpha-Reductase Deficiency”. WebMD. Information & Perspective Medicine & Ailments CME & Schooling Academy Seek the advice of, Medicine & Ailments > Pediatrics: Normal Drugs.
  76. ^ Freudenheim M (16 February 1992). “Retaining the Pipeline Crammed at Merck”. The New York Instances.
  77. ^ Cordes E (2014). Hallelujah Moments: Tales of Drug Discovery. Oxford College Press. ISBN 9780199337149.
  78. ^ “Previous Inventor of the 12 months Award Winners”. ipoef.org. Mental Property House owners Schooling Basis. Retrieved 21 June 2020.
  79. ^ Burger A, Abraham DJ (20 February 2003). Burger’s Medicinal Chemistry and Drug Discovery, Autocoids, Diagnostics, and Medicine from New Biology. Wiley. p. 439. ISBN 978-0-471-37030-7.
  80. ^ Doherty AM (2003). Annual Experiences in Medicinal Chemistry. Educational Press. pp. 353–. ISBN 978-0-12-040538-1.
  81. ^ Diamanti-Kandarakis E, Tolis G, Duleba AJ (1995). “Androgens and therapeutic features of antiandrogens in girls”. J. Soc. Gynecol. Investig. 2 (4): 577–92. doi:10.1177/107155769500200401. PMID 9420861. S2CID 32242838.
  82. ^ British nationwide formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 769. ISBN 9780857113382.
  83. ^ “NADAC as of 2019-02-27”. Facilities for Medicare and Medicaid Providers. Retrieved Three March 2019.
  84. ^ a b Index Nominum 2000: Worldwide Drug Listing. Taylor & Francis. 2000. p. 443. ISBN 978-3-88763-075-1.
  85. ^ a b I.Okay. Morton; Judith M. Corridor (6 December 2012). Concise Dictionary of Pharmacological Brokers: Properties and Synonyms. Springer Science & Enterprise Media. pp. 121–. ISBN 978-94-011-4439-1.
  86. ^ a b Barrie W. Bycroft; David J. Payne (9 August 2013). Dictionary of Antibiotics and Associated Substances: with CD-ROM, Second Version. CRC Press. pp. 816–. ISBN 978-1-4822-8215-3.
  87. ^ a b c d “Finasteride”.
  88. ^ “Main Patent Expirations for Chosen Excessive Income Medicine”. RxNews. Prescription Options. Archived from the unique on 21 March 2008.
  89. ^ FDA. “Patent Expiration for Propecia”. Orange Guide: Accredited Drug Merchandise with Therapeutic Equivalence Evaluations.
  90. ^ Margo J (26 September 2012). “Taking a look at care with a vital eye”. Australian Monetary Assessment. Archived from the unique on 14 November 2012.
  91. ^ Daniel Marchalik (Four February 2017). “Look ahead to these potential unwanted effects in drug Trump reportedly takes for hair loss”. Miami Herald. Retrieved 9 December 2018.
  92. ^ Sandomir R (19 January 2006). “Pores and skin Deep; Combating Baldness, and Now an Olympic Ban”. The New York Instances. Retrieved 2 Could 2010.
  93. ^ a b Employees (28 October 2008). “WADA removes Finasteride from ban checklist”. The Australian.
  94. ^ Employees (9 October 2008). “WADA takes Romario’s drug off banned checklist”. Sydney Morning Herald.
  95. ^ “Deferral of Blood and Plasma donors – Drugs” (PDF). FDA. 28 July 1993. Retrieved Four February 2017.
  96. ^ “Anti-Androgens – Joint United Kingdom Blood Transfusion and Tissue Transplantation Providers Skilled Advisory Committee”. www.transfusionguidelines.org. 1 June 2007. Retrieved 13 Could 2020.
  97. ^ Schechter, Anna R. (1 Could 2018). “Trump physician Harold Bornstein says bodyguard, lawyer ‘raided’ his workplace, took medical information”. NBC Information. Retrieved 27 October 2018.
  98. ^ Altman LK (1 February 2017). “Donald Trump’s Longtime Physician Says President Takes Hair-Progress Drug”. The New York Instances. Retrieved 25 February 2017.
  99. ^ “Trump physician reveals secret to US president’s hair”. The Guardian. 2 February 2017. Retrieved 13 Could 2020.
  100. ^ Lee SW, Juhasz M, Mobasher P, Ekelem C, Mesinkovska NA (April 2018). “A Systematic Assessment of Topical Finasteride within the Therapy of Androgenetic Alopecia in Males and Ladies”. J Medicine Dermatol. 17 (4): 457–463. PMC 6609098. PMID 29601622.
  101. ^ a b Marks DH, Prasad S, De Souza B, Burns LJ, Senna MM (December 2019). “Topical Antiandrogen Therapies for Androgenetic Alopecia and Zits Vulgaris”. Am J Clin Dermatol. 21 (2): 245–254. doi:10.1007/s40257-019-00493-z. PMID 31832993. S2CID 209331373.
  102. ^ F. William Danby (27 January 2015). Zits: Causes and Sensible Administration. John Wiley & Sons. pp. 147–. ISBN 978-1-118-23277-4.
  103. ^ a b Marchetti PM, Barth JH (March 2013). “Scientific biochemistry of dihydrotestosterone”. Ann. Clin. Biochem. 50 (Pt 2): 95–107. doi:10.1258/acb.2012.012159. PMID 23431485. S2CID 8325257.
  104. ^ a b c Hu AC, Chapman LW, Mesinkovska NA (January 2019). “The efficacy and use of finasteride in girls: a scientific evaluation”. Int. J. Dermatol. 58 (7): 759–776. doi:10.1111/ijd.14370. PMID 30604525. S2CID 58555908.
  105. ^ Alikhan A, Lynch PJ, Eisen DB (April 2009). “Hidradenitis suppurativa: a complete evaluation”. J. Am. Acad. Dermatol. 60 (4): 539–61, quiz 562–3. doi:10.1016/j.jaad.2008.11.911. PMID 19293006.
  106. ^ Riis PT, Ring HC, Themstrup L, Jemec GB (December 2016). “The Function of Androgens and Estrogens in Hidradenitis Suppurativa – A Systematic Assessment”. Acta Dermatovenerol Croat. 24 (4): 239–249. PMID 28128074.
  107. ^ Nomani H, Mohammadpour AH, Moallem SM, YazdanAbad MJ, Barreto GE, Sahebkar A (December 2019). “Anti-androgen medication within the therapy of obsessive-compulsive dysfunction: a scientific evaluation”. Curr Med Chem. doi:10.2174/0929867326666191209142209. PMID 31814547.

Exterior hyperlinks[edit]

  • “Finasteride”. Drug Data Portal. U.S. Nationwide Library of Drugs.


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