フィナステリド
|
|
IUPAC命名法による物質名 |
N-(1,1-dimethylethyl)-3-oxo-
(5α,17β)-4-azaandrost-1-ene-17-carboxamide
|
臨床データ |
胎児危険度分類 |
|
法的規制 |
- UK: 処方箋のみ (POM)
- US: ℞-only
|
投与方法 |
経口 |
薬物動態データ |
生物学的利用能 |
63% |
代謝 |
肝臓 |
半減期 |
年配者: 8時間
成人: 6時間 |
排泄 |
代謝物として糞(57%)、尿(39%) |
識別 |
CAS番号 |
98319-26-7 |
ATCコード |
G04CB01 D11AX10 |
PubChem |
CID: 194453 |
DrugBank |
APRD00632 |
ChemSpider |
51714 |
KEGG |
D00321 |
化学的データ |
化学式 |
C23H36N2O2 |
分子量 |
372.549 g/mol |
フィナステリド |
形状 |
白色結晶性粉末 |
水への溶解度 |
ほぼ不溶 |
出典 |
プロペシア添付文書 |
フィナステリド(finasteride, 商品名 Proscar, Propecia, Fincar, Finpecia, Finax, Finast, Finara, Prosteride)は米メルク社が開発した抗アンドロゲン薬の1つであり、男性ホルモンテストステロンをDHT(ジヒドロテストステロン)へ変換する酵素である2型5-α還元酵素を阻害することによって作用する。前立腺肥大症に対して低用量で、前立腺癌に対しては高用量で使用される。ドキサゾシンと組み合わせて用いることにより、前立腺肥大症の病状が進行する危険性を低減することが示されている。
また男性型脱毛症(AGA)の治療薬として、プロスカー、プロペシアの商品名で多くの国で発売されている。日本ではプロペシアのみが、米メルク社の日本法人であるMSD社(旧万有製薬)から発売されている。同作用の薬にデュタステリド(dutasteride, 商品名 アボルブ)があるが、こちらはフィナステリドの作用しない1型5-α還元酵素をも阻害する上、2型5-α還元酵素もフィナステリドの3倍強く阻害するなど作用が強い。
目次
- 1 開発の経緯
- 2 前立腺疾患
- 3 脱毛症
- 3.1 作用機序
- 3.2 副作用
- 3.3 服用方法
- 3.4 価格
- 3.5 AGAチェック
- 3.6 ドーピング
- 4 脚注
- 5 関連項目
- 6 外部リンク
開発の経緯
1991年にフィナステリドの開発が始まり、初め1992年に米国で前立腺肥大の治療薬としてプロスカー(5mg錠)の商品名で認可された。しかし、その後1mg用量での研究によって、男性型の脱毛症において毛髪の成長が見られることが明らかにされ、1997年12月22日、FDAはフィナステリドを男性型脱毛症の治療薬として認可した。2006年現在では世界60か国以上で承認されている。日本では、1年間の臨床試験を終え、2005年10月に厚生労働省に承認され、同年12月に発売となった。日本では前立腺肥大症治療薬としては認可されていない。
前立腺疾患
前立腺癌予防試験 (Prostate Cancer Prevention Trial, PCPT) において、(脱毛症への通常の処方量よりも多いが)前立腺癌に対しては一般的な処方である5mg/日の投与では、プラセボ(偽薬)を与えた患者よりも25%前立腺癌の進行が遅れた、という結果が得られた[1]。しかしながら、フィナステリドを与えた患者のうち進行が見られた場合については、癌の増加と拡大の率がプラセボより大きかった。その原因については明らかになっていない。研究者はそれらの患者の癌が特に強いものであるかについて、経過を観察している。低用量でもこのような効果があるのかは不明である。
作用機序
DHTは前立腺の受容体と結びつき、成長を促して肥大や癌を招くが、このDHTの生成を阻害することで、前立腺の正常な体積を維持する。なお慢性前立腺炎には効果が薄く、デュタステリドが用いられることが多い。
脱毛症
DHTによる脱毛作用を抑止するものであり、決して発毛に作用する薬ではないが、臨床試験では服用者の多くにある程度の発毛が認められる。日本では2005年12月に万有製薬(現:MSD)から発売された。海外では既に60か国以上で承認されている。DHTという髪の成長を妨げる原因物質を抑えることで効果を発揮する。アメリカ食品医薬品局 (FDA) が認めた男性型脱毛症(いわゆる、若ハゲ)に有効な薬は、このプロペシアとミノキシジル(商品名ロゲインなど)のみである。なお、男性型脱毛症以外の脱毛症(円形脱毛症など)には効果はない。
作用機序
DHTは皮脂腺の受容体と結びつき、過剰な皮脂を分泌させ、毛穴を塞いで男性型脱毛を誘発するが、このDHTの生成を阻害することで効果を発揮する。
男性型脱毛症は、時間と共に進行していくものであり、髪が薄くなっていくことを抑える事がまず大切である。少なくとも進行をくい止められたという意味では、フィナステリドは、98%の人に3年間効果があった。髪が増えてくる人も多く、国内の臨床試験では半年で48%、1年で58%、2年では68%、3年で78%と髪が増える人が経時的に増えていった。また髪が増えるだけでなく、髪の質(長さ、太さ)なども改善することも分かっている。頭頂部(頭のてっぺん)だけでなく、髪の毛の生え際などの前髪にも効果がある点も、従来の育毛剤とは異なる。
副作用
国内臨床試験時では、1mgのプロペシアで胃部不快感、性欲減退など6%程度の副作用が認められたが、この副作用の発現頻度は、プラセボで起こった副作用の頻度と同程度だとの意見がある[2]。特に重篤な副作用は報告されていないとされているが、万有製薬(現:MSD)はプロペシア錠を飲むことによって、頻度不明ながら、肝機能障害が起こり得ると重大な副作用を追加した(2007年9月)。
1%以上5%未満に性欲減退の副作用が発現する他、1%未満に勃起機能不全、射精障害、精液量減少が発現する[3]。その他、発現率不明の副作用として、睾丸痛、男性不妊症・精液の質低下(精子濃度減少、無精子症、精子運動性低下、精子形態異常等)、乳房圧痛、乳房肥大、抑鬱症状、眩暈、そう痒症、蕁麻疹、発疹、血管浮腫(口唇、舌、咽喉及び顔面腫脹を含む)、AST(GOT)上昇、ALT(GPT)上昇、γ-GTP上昇が添付文書に記載されている[3]。
服用方法
0.2mg又は1mg錠を1日1回服用する。なお、必要に応じて適宜増減できるが、1日1mgを上限とする。服用時間は自由である。服用は成人の男性に限られる。女性、未成年は服用できない。
禁忌(下記の人には使えない)
- 本剤の成分に対し過敏症の既往歴のある患者
- 妊婦又は妊娠している可能性のある婦人及び授乳中の婦人
また服用中は献血していはいけない。献血には、最低でも1ヶ月の休薬期間をとる必要がある[4]。
価格
医師の処方が必要である。また医師の処方する他の医療用医薬品とは異なり、薬価基準未収載品であるため健康保険で算定されない。そのため、薬剤費を含め、診療費、調剤料などは全額自己負担になり、その負担額は医療機関によって異なる(卸からの仕入れ価格などにより病院、薬局ごとに異なる)。販売元の万有製薬(現:MSD)では、参考薬剤価格として1錠250円(税抜き)という目安を出しているが、薬剤費とその他の負担額(診察料、調剤料)などを含めると1か月9,500円~13,000円程度のところが多いとされる。都市圏ほど安く処方する医療機関が多い。
AGAチェック
AGAチェックは血液や毛髪のDNA配列を解析することによってAGA(男性型脱毛症)のリスクとフィナステリドの効果を判定する検査であり、専門の医療機関で受けることができる。
AGAの主な原因とされているDHTは毛乳頭細胞のX染色体上にあるレセプター(男性ホルモン受容体)に作用して症状を発現させるが、X染色体にはこのレセプターを覆い隠すような三次元構造を持つ特殊なDNA配列が存在する。「c,a,g」という三つの塩基が繰り返すことから「cagリピート」と呼ばれるこの構造は長さ(繰り返し回数)に個人差があり、生まれつきcagリピートの長さが異なる。
cagリピートが長ければDHTが作用しにくくなるためAGAのリスクは低く、短ければリスクが高くなる。cagリピートの長さはフィナステリドの効果にも影響する。cagリピートが短ければDHTの作用を強く受けるため、DHTの生成を抑える薬剤であるフィナステリドの効果は高くなる。AGAチェックはこのcagリピートを測定するものであり、血液を採取するか、後頭部の毛髪を10本程度採取して検査する。cagリピートは年齢によって変化することがないため、この検査は1回だけ受ければいい。
AGAチェックは女性が受けることもできるが、女性に対するフィナステリドの使用には制限が多い。特に妊娠中の女性については胎児へのリスクが高く禁忌である。
ドーピング
フィナステリドは、体内で男性ホルモンに影響し筋肉増強剤の使用を隠す効果があるため、世界アンチ・ドーピング機関などでドーピング剤として認定されていたが、2009年1月1日より世界アンチ・ドーピング機関は禁止リストより除外しており現在ではドーピングに当たらないとの判断がなされている[5]。
2007年3月13日、オーストラリア元代表のサッカーDF選手スタン・ラザリディスがドーピング検査で陽性反応を示したと所属サッカークラブパース・グローリーが発表した。報道では、彼が利用していた発毛薬で使われるフィナステリドに反応したと報じた。米国スケルトン男子のザック・ランドがフィナステリドが原因でトリノ五輪出場を逃した。
日本では、2007年8月10日にソフトバンク所属のリック・ガトームソン投手がドーピング検査でフィナステリドに対し陽性反応を示し20日間の出場停止処分が下された。
2009年1月1日、分析技術の進歩によりフィナステリドを使用しても禁止物質の使用を判別することが可能となったため、世界アンチ・ドーピング機関は禁止リストから除外した。
脚注
- ^ "Can Prostate Cancer Be Prevented?" American Cancer Society, May 25, 2005.
- ^ 川島眞 他 臨床皮膚科 2006 ; 60(6): 521-530.
- ^ a b “プロペシア錠0.2mg/プロペシア錠1mg 添付文書” (2014年3月). 2015年9月14日閲覧。
- ^ "東京都赤十字血液センター 献血の基準"
- ^ "World Anti-Doping Agency Q&A: Status of Finasteride"
関連項目
- 男性型脱毛症
- 脱毛の治療
- デュタステリド(グラクソ・スミスクライン社の5α還元酵素阻害薬、商品名アボルブ®)
- メルク(MSD)社
外部リンク
- メルク(MSD)社 プロペシア(英語)
- メルク(MSD)社 プロペシア(日本語)
- メルク(MSD)社 プロペシア「医療関係者向け」(日本語)
Finasteride (INN, USAN, BAN)
|
|
Systematic (IUPAC) name |
N-(1,1-dimethylethyl)-3-oxo-
(5α,17β)-4-azaandrost-1-ene-17-carboxamide
|
Clinical data |
Trade names |
Propecia, Proscar |
AHFS/Drugs.com |
monograph |
MedlinePlus |
a698016 |
Pregnancy
category |
- X (will cause birth defects in a fetus)
|
Legal status |
- UK: POM (Prescription only)
- US: ℞-only
|
Routes of
administration |
Oral |
Pharmacokinetic data |
Bioavailability |
63% |
Metabolism |
Hepatic |
Biological half-life |
Elderly: 8 hours
Adults: 6 hours |
Excretion |
Feces (57%) and urine (39%) as metabolites |
Identifiers |
CAS Number |
98319-26-7 Y |
ATC code |
G04CB01 D11AX10 |
PubChem |
CID: 57363 |
IUPHAR/BPS |
6818 |
DrugBank |
DB01216 Y |
ChemSpider |
51714 Y |
UNII |
57GNO57U7G Y |
KEGG |
D00321 Y |
ChEBI |
CHEBI:5062 Y |
ChEMBL |
CHEMBL710 Y |
Chemical data |
Formula |
C23H36N2O2 |
Molecular mass |
372.549 g/mol |
SMILES
-
O=C(NC(C)(C)C)[C@@H]2[C@]1(CC[C@H]3[C@H]([C@@H]1CC2)CC[C@H]4NC(=O)\C=C/[C@]34C)C
|
InChI
-
InChI=1S/C23H36N2O2/c1-21(2,3)25-20(27)17-8-7-15-14-6-9-18-23(5,13-11-19(26)24-18)16(14)10-12-22(15,17)4/h11,13-18H,6-10,12H2,1-5H3,(H,24,26)(H,25,27)/t14-,15-,16-,17+,18+,22-,23+/m0/s1 Y
-
Key:DBEPLOCGEIEOCV-WSBQPABSSA-N Y
|
(verify) |
Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used for the treatment of benign prostatic hyperplasia (BPH) and male pattern baldness (MPB).[1][2] It is a type II and type III 5α-reductase inhibitor;[3] 5α-reductase, an enzyme, converts testosterone to dihydrotestosterone (DHT).[2]
Contents
- 1 Medical uses
- 1.1 Benign prostatic hyperplasia
- 1.2 Male pattern baldness
- 1.3 Off-label uses
- 2 Contraindications
- 3 Adverse effects
- 4 Mechanism of action
- 5 Physical and chemical properties
- 6 History
- 7 Society and culture
- 8 Research
- 9 See also
- 10 References
- 11 External links
Medical uses
Benign prostatic hyperplasia
Physicians use finasteride for the treatment of BPH, informally known as an enlarged prostate. Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up during the night to urinate, hesitation at the start of urination, and decreased urinary flow. It provides less symptomatic relief than alpha-1 blockers such as tamsulosin and symptomatic relief is slower in onset (six months or more of treatment with finasteride may be required to determine the therapeutic results of treatment). Symptomatic benefits are mainly seen in those with prostate volume > 40 cm2. In long-term studies finasteride but not alpha-1 inhibitors reduce the risk of acute urinary retention (−57% at 4 years) and the need for surgery (−54% at 4 years). If the drug is discontinued, any therapeutic benefits reverse within about 6–8 months.[4][5][6]
Male pattern baldness
Finasteride is used to treat male pattern hair loss (androgenetic alopecia) in men only.[7] Treatment provides about 30% improvement in hair loss after six months of treatment, and effectiveness only persists as long as the drug is taken.[8]
Off-label uses
Finasteride is sometimes used in hormone replacement therapy for male-to-female transsexuals in combination with a form of estrogen due to its antiandrogen properties. However, little clinical research of finasteride use for this purpose has been conducted and evidence of efficacy is limited.[9]
Contraindications
Finasteride is not approved for use in women, especially due to risks of birth defects in a fetus. It is classified in the FDA pregnancy category X.[7]
Adverse effects
Adverse effects from finasteride are rare.[4] The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer, as the treatment of BPH lowers PSA (prostate-specific antigen), which could mask the development of prostate cancer.[10][11]
Although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not increased, there are post-marketing reports of breast cancer in association with its use. Available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers.[7][12]
The effect of finasteride on sexual function is controversial. There are case reports of persistent diminished libido or erectile dysfunction after stopping the drug and the FDA has updated the label to inform healthcare professionals of these reports.[8][13] A 2010 review found moderate quality evidence that finasteride increased the risk of sexual dysfunction, but not that people stopped using it because of sexual side effects.[14]
A 2015 meta analysis found none of the clinical trials had adequate safety reporting and did not provide sufficient information to establish the safety profile for finasteride's treatment of hairloss. The study concluded the existing clinical trials of finasteride for hair loss provide very limited information on toxicity,are of poor quality, and seem to be systematically biased toward under detection of adverse events. Moreover, the trials submitted to the FDA for approval for hair loss excluded most men who would normally be prescribed finasteride for androgenic alopecia.[15][16]
When finasteride was originally approved for hair loss in 1997, the FDA approval review reported that it appears well tolerated, with the most common side effects being related to sexual function.[17] In many people these side effects resolve if the medication is stopped and occasionally resolve even if the medication is continued.[17] They additionally state "the sexual functioning questionnaire seems to have given a sensitive reflection of the disturbance on sexual functioning".[17]
Mechanism of action
Finasteride is a 5α-reductase inhibitor, specifically the type II and III isoenzymes.[3][18] By inhibiting 5α-reductase, finasteride prevents conversion of testosterone to dihydrotestosterone (DHT) by the type II and III isoenzymes, resulting in a decrease in serum DHT levels by about 65–70% and in prostate DHT levels by up to 85–90%,[3][19] where expression of the type II isoenzyme dominates. Unlike triple inhibitors of all three isoenzymes of 5α-reductase like dutasteride which can reduce DHT levels in the entire body by more than 99%,[3] finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the 5α-reductase type I isoenzyme, with 100-fold less affinity for I as compared to II.[7] In addition to blocking the type II and III isoenzymes, finasteride competitively inhibits the 5β-reductase type II isoenzyme,[20] though this is not believed to affect androgen metabolism.[citation needed]
By blocking DHT production, finasteride reduces androgen activity in the scalp. In the prostate, inhibition of 5α-reductase reduces prostate volume, which improves BPH and reduces risk of prostate cancer. Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.[21]
DHT helps activate the GABAA receptor, which functions to tamp down signaling among neurons; because finasteride prevents the formation of DHT, it may contribute to a reduction of GABAA activity. Reduced GABAA has been implicated in depression, anxiety, and sexual dysfunction.[22][23][24]
Physical and chemical properties
Finasteride is a 4-azasteroid analogue of testosterone and is lipophilic.[25]
Drug trade names include Propecia and Proscar, the former marketed for male pattern baldness (MPB) and the latter for benign prostatic hyperplasia (BPH), both are products of Merck & Co. There is 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck's patent on finasteride for the treatment of BPH expired on June 19, 2006.[26] Merck was awarded a separate patent for the use of finasteride to treat MPB. This patent expired in November 2013.[27]
History
In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on birth defects. She reported on a group of intersex children in the Caribbean who appeared sexually ambiguous at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic after onset of puberty. Her research group found these children shared a genetic mutation, causing deficiency of the 5α-reductase enzyme and male hormone dihydrotestosterone (DHT), which was found to have been the etiology behind abnormalities in male sexual development. Upon maturation, these individuals were observed to have smaller prostates which were underdeveloped, and were also observed to lack incidence of male pattern baldness.[28][29] It was developed under the code name MK-906.[citation needed]
In 1975, copies of Imperato-McGinley's presentation were seen by P. Roy Vagelos, who was then serving as Merck's basic-research chief. He was intrigued by the notion that decreased levels of DHT led to the development of smaller prostates. Dr. Vagelos then sought to create a drug which could mimic the condition found in these children to treat older men who were suffering from benign prostatic hyperplasia.[30]
In 1992, finasteride (5 mg) was approved by the U.S. Food and Drug Administration (FDA) for treatment of BPH, which Merck marketed under the brand name Proscar.[citation needed]
In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg) for treatment of MPB, which was marketed under the brand name Propecia.[citation needed]
Society and culture
In 2005, the World Anti-Doping Agency banned finasteride because a laboratory in Germany discovered the drug could be used to mask steroid abuse.[31] It was removed from the list effective January 1, 2009, after improvements in testing methods made the ban unnecessary.[32] Notable athletes who used finasteride for hair loss and were banned from international competition include skeleton racer Zach Lund, bobsledder Sebastien Gattuso, footballer Romário and ice hockey goaltender José Théodore.[32][33]
According to a 2012 article in the Australian Financial Review, men in the US and Canada concerned about persistent sexual side effects of finasteride had "coined the phrase 'post finasteride syndrome', which they say is characterised by sexual, neurological, hormonal and psychological side effects that can persist in men who have taken finasteride for hair loss or an enlarged prostate".[34][35]
In 2012, a health advocacy group called the Post-Finasteride Syndrome Foundation was formed with the primary goal of finding a cure for the reported syndrome and a secondary goal of raising awareness.[34]
Research
Finasteride has been clinically tested for baldness in women; the results were no better than placebo.[36]
See also
- Alfatradiol
- Antineurosteroid
- Ketoconazole
- Minoxidil
- Saw palmetto extract
References
- ^ J. Buckingham (1987). Dictionary of Organic Compounds. CRC Press. p. 3147. ISBN 978-0-412-54090-5.
- ^ a b I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 121, 246. ISBN 978-94-011-4439-1.
- ^ a b c d Yamana K, Labrie F, Luu-The V (January 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). doi:10.1515/hmbci.2010.035.
- ^ a b Tacklind, J; Fink, HA; Macdonald, R; Rutks, I; Wilt, TJ (Oct 6, 2010). "Finasteride for benign prostatic hyperplasia.". The Cochrane database of systematic reviews (10): CD006015. doi:10.1002/14651858.CD006015.pub3. PMID 20927745.
- ^ Proscar label
- ^ "Treatment of Non-neurogenic Male LUTS | Uroweb".
- ^ a b c d "Propecia label" (PDF).
- ^ a b Varothai, S; Bergfeld, WF (Jul 2014). "Androgenetic alopecia: an evidence-based treatment update.". American journal of clinical dermatology 15 (3): 217–30. doi:10.1007/s40257-014-0077-5. PMID 24848508.
- ^ Knezevich EL, Viereck LK, Drincic AT (January 2012). "Medical management of adult transsexual persons". Pharmacotherapy 32 (1): 54–66. doi:10.1002/PHAR.1006. PMID 22392828.
- ^ FDA. Posted 9 June 2011. 5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer
- ^ Walsh PC (April 2010). "Chemoprevention of prostate cancer". The New England Journal of Medicine 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
- ^ Medicines and Healthcare products Regulatory Agency Drug Safety Update. December 2009 Finasteride: potential risk of male breast cancer
- ^ FDA (11 April 2012). "Questions and Answers: Finasteride Label Changes". US FDA. Retrieved 26 October 2014.
- ^ Mella, JM; Perret, MC; Manzotti, M; Catalano, HN; Guyatt, G (October 2010). "Efficacy and safety of finasteride therapy for androgenetic alopecia: a systematic review.". Archives of Dermatology 146 (10): 1141–50. doi:10.1001/archdermatol.2010.256. PMID 20956649.
- ^ Belknap, SM; Aslam, I; Kiguradze, T; Temps, WH; Yarnold, PR; Cashy, J; Brannigan, RE; Micali, G; Nardone, B; West, DP (1 April 2015). "Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis.". JAMA dermatology 151: 600–6. doi:10.1001/jamadermatol.2015.36. PMID 25830296.
- ^ Moore, TJ (1 April 2015). "Finasteride and the Uncertainties of Establishing Harms.". JAMA dermatology 151: 585–6. doi:10.1001/jamadermatol.2015.37. PMID 25831198.
- ^ a b c FDA. "Summary of Key Safety Findings" (PDF). p. 98.
- ^ Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M (February 2010). "An overview on 5alpha-reductase inhibitors". Steroids 75 (2): 109–53. doi:10.1016/j.steroids.2009.10.005. PMID 19879888.
- ^ Bartsch G, Rittmaster RS, Klocker H (April 2000). "Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia". European Urology 37 (4): 367–80. doi:10.1159/000020181. PMID 10765065.
- ^ Drury JE, Di Costanzo L, Penning TM, Christianson DW (July 2009). "Inhibition of human steroid 5beta-reductase (AKR1D1) by finasteride and structure of the enzyme-inhibitor complex". The Journal of Biological Chemistry 284 (30): 19786–90. doi:10.1074/jbc.C109.016931. PMC 2740403. PMID 19515843.
- ^ Robaire B, Henderson NA (May 2006). "Actions of 5alpha-reductase inhibitors on the epididymis". Molecular and Cellular Endocrinology 250 (1-2): 190–5. doi:10.1016/j.mce.2005.12.044. PMID 16476520.
- ^ Finn DA, Beadles-Bohling AS, Beckley EH; et al. (2006). "A new look at the 5alpha-reductase inhibitor finasteride". CNS Drug Reviews 12 (1): 53–76. doi:10.1111/j.1527-3458.2006.00053.x. PMID 16834758.
- ^ Römer B, Gass P (December 2010). "Finasteride-induced depression: new insights into possible pathomechanisms". Journal of Cosmetic Dermatology 9 (4): 331–2. doi:10.1111/j.1473-2165.2010.00533.x. PMID 21122055.
- ^ Gunn BG, Brown AR, Lambert JJ, Belelli D (2011). "Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress". Frontiers in Neuroscience 5: 131. doi:10.3389/fnins.2011.00131. PMC 3230140. PMID 22164129.
- ^ Azeem A, Khan ZI, Aqil M, Ahmad FJ, Khar RK, Talegaonkar S (May 2009). "Microemulsions as a surrogate carrier for dermal drug delivery". Drug Development and Industrial Pharmacy 35 (5): 525–47. doi:10.1080/03639040802448646. PMID 19016057.
- ^ Primary Patent Expirations for Selected High Revenue Drugs
- ^ fda.gov | Patent Expiration for Propecia
- ^ Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (December 1974). "Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism". Science 186 (4170): 1213–5. doi:10.1126/science.186.4170.1213. PMID 4432067.
- ^ Emerick JE et al. for WebMD. Last Updated Updated: 29 May 2014 5-Alpha-Reductase Deficiency
- ^ Freudenheim, Milt (February 16, 1992). "Keeping the Pipeline Filled at Merck". The New York Times.
- ^ Sandomir, Richard (2006-01-19). "Skin Deep; Fighting Baldness, and Now an Olympic Ban". The New York Times. Retrieved 2010-05-02.
- ^ a b Staff, The Australian. 28 October 2008 WADA removes Finasteride from ban list
- ^ Staff, Sydney Morning Herald. 9 October 2008 WADA takes Romario's drug off banned list
- ^ a b Jill Margo for the Australian Financial Review. 26 Sept 2012 Looking at care with a critical eye
- ^ Post-Finasteride Syndrome Foundation official website
- ^ Levy, LL; Emer, JJ (Aug 29, 2013). "Female pattern alopecia: current perspectives.". International journal of women's health 5: 541–56. doi:10.2147/IJWH.S49337. PMC 3769411. PMID 24039457.
External links
- Proscar | Official website
- Propecia | Official website
Androgens and antiandrogens
|
|
Androgens |
Agonists |
- Anabolic steroids (see here instead)
- Androgenic progestins (e.g., norethisterone, levonorgestrel, medroxyprogesterone acetate)
- Androstanolone
- Androstenediol
- Androstenedione
- DHEA
- DHEA sulfate
- Dihydrotestosterone
- Fluoxymesterone
- Mesterolone
- Methyltestosterone
- Testosterone#
- Testosterone acetate
- Testosterone capropate
- Testosterone cypionate
- Testosterone decanoate
- Testosterone enanthate
- Testosterone isocaproate
- Testosterone phenylpropionate
- Testosterone propionate
- Testosterone undecanoate
- Tibolone
|
|
SARMs |
- AC-262,356§
- Andarine§
- BMS-564,929§
- Enobosarm (ostarine)§
- LGD-2226§
- LGD-3303§
- S-23§
- S-40503§
|
|
|
Antiandrogens |
Antagonists |
- Abiraterone acetate
- Apalutamide†
- Bicalutamide
- Canrenoic acid
- Canrenone
- Chlormadinone acetate
- Cimetidine
- Cyproterone acetate
- Drospirenone
- Enzalutamide
- EPI-001§
- Flutamide
- Galeterone†
- Ketoconazole
- Megestrol acetate
- Nilutamide
- Nomegestrol acetate
- ODM-201†
- Potassium canrenoate
- Spironolactone
- Topilutamide (fluridil)
- Valproic acid
- VT-464†
|
|
Enzyme inhibitors |
5α-Reductase |
- Alfatradiol
- Chlormadinone acetate
- Dutasteride
- Finasteride
- Saw palmetto extract
|
|
CYP17A1 |
- Abiraterone acetate
- Cyproterone acetate
- Danazol
- Galeterone†
- Gestrinone
- Ketoconazole
- Orteronel†
- Spironolactone
- VT-464†
|
|
Others |
- Abiraterone acetate
- Aminoglutethimide
- Cyproterone acetate
- Danazol
- Gestrinone
- Ketoconazole
- Mitotane
- Trilostane
|
|
|
Antigonadotropins |
- Anabolic steroids (e.g., nandrolone, oxandrolone)
- Estrogens (e.g., estradiol)
- GnRH agonists (e.g., leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Progestogens (incl. allylestrenol, chlormadinone acetate, cyproterone acetate, delmadinone acetate, dydrogesterone, medroxyprogesterone acetate, megestrol acetate, nomegestrol acetate, norethisterone acetate, progesterone, spironolactone)
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|
|
-
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
Index of reproductive medicine
|
|
Description |
- Anatomy
- Physiology
- Development
- sex determination and differentiation
|
|
Disease |
- Infections
- Congenital
- Neoplasms and cancer
- male
- female
- gonadal
- germ cell
- Other
- Symptoms and signs
|
|
Treatment |
- Procedures
- Drugs
- benign prostatic hypertrophy
- erectile dysfunction and premature ejaculation
- sexual dysfunction
- infection
- hormones
- androgens
- estrogens
- progestogens
- GnRH
- prolactin
- Assisted reproduction
- Birth control
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|
|
Drugs used in benign prostatic hyperplasia (G04C)
|
|
5α-reductase inhibitors |
|
|
Alpha blockers (α1) |
- Alfuzosin
- Doxazosin
- Silodosin
- Tamsulosin
- Terazosin
|
|
Herbals |
- Pygeum africanum
- Saw palmetto extract
|
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Other |
|
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Index of reproductive medicine
|
|
Description |
- Anatomy
- Physiology
- Development
- sex determination and differentiation
|
|
Disease |
- Infections
- Congenital
- Neoplasms and cancer
- male
- female
- gonadal
- germ cell
- Other
- Symptoms and signs
|
|
Treatment |
- Procedures
- Drugs
- benign prostatic hypertrophy
- erectile dysfunction and premature ejaculation
- sexual dysfunction
- infection
- hormones
- androgens
- estrogens
- progestogens
- GnRH
- prolactin
- Assisted reproduction
- Birth control
|
|
|
Other dermatological preparations (D11)
|
|
Medicated shampoos |
- Cetrimide
- Cadmium compounds
- Ketoconazole
- Povidone-iodine
- Selenium compounds
- Sulfur compounds
- Xenysalate
|
|
Other dermatologicals |
Seborrhoeic dermatitis/dandruff |
- Lithium succinate
- Pyrithione zinc
|
|
Skin whitening/depigmenting |
- Hydroquinone
- Mequinol
- Monobenzone
|
|
Skin darkening/pigmenting |
- Afamelanotide
- Melanotan II
|
|
Anti-inflammatory/Immunomodulators |
- Oxaceprol
- Gamolenic acid
- Pimecrolimus
- Tacrolimus
- Alitretinoin
|
|
Baldness treatments |
- 5α-Reductase inhibitors
- Alfatradiol
- Finasteride
- Dutasteride
- Saw palmetto extract
- Antiandrogens
- Spironolactone
- Topilutamide (fluridil)
- Potassium channel openers
|
|
Hair growth inhibitors |
- Eflornithine
- 5α-Reductase inhibitors
- Antiandrogens
- Spironolactone
- Cyproterone acetate
- Flutamide
- Bicalutamide
- Ketoconazole
|
|
Other |
- Calcium gluconate
- Magnesium sulfate
- Tiratricol
|
|
|
Index of skin
|
|
Description |
- Anatomy
- Physiology
- Development
|
|
Disease |
- Infections
- Vesiculobullous
- Dermatitis and eczema
- Papulosquamous
- Urticaria and erythema
- Radiation-related
- Pigmentation
- Mucinoses
- Keratosis, ulcer, atrophy, and necrobiosis
- Vasculitis
- Fat
- Neutrophilic and eosinophilic
- Congenital
- Neoplasms and cancer
- nevi and melanomas
- epidermis
- dermis
- Symptoms and signs
- Terminology
|
|
Treatment |
- Procedures
- Drugs
- antibiotics
- disinfectants
- emollients and protectives
- itch
- psoriasis
- other
- Wound and ulcer
|
Index of skin appendages
|
|
Description |
- Anatomy
- Physiology
- Development
|
|
Disease |
- Congenital
- Neoplasms and cancer
- Other
- Symptoms and signs
|
|
Treatment |
|
|
|
Androgenics
|
|
Receptor
(ligands) |
AR
|
Agonists
|
|
|
Mixed (SARMs)
|
- AC-262,356
- Andarine
- BMS-564,929
- Enobosarm (ostarine)
- LGD-2226
- LGD-3303
- LGD-4033
- RAD140
- S-23
- S-40503
- TFM-4AS-1
|
|
Antagonists
|
- 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- Abiraterone
- Abiraterone acetate
- Apalutamide
- AZD-3514
- Bisphenols (e.g., BADGE, BFDGE, bisphenol A, bisphenol F, bisphenol S)
- Benorterone
- Bicalutamide
- BMS-641,988
- BOMT
- Canrenoic acid
- Canrenone
- Chlormadinone acetate
- Cimetidine
- Cioteronel
- Clometerone
- Cyproterone
- Cyproterone acetate
- Delanterone
- DDT (via metabolite p,p’-DDE)
- Dieldrin
- Dienogest
- Drospirenone
- Endosulfan
- Enzalutamide
- EPI-001
- Epitestosterone
- Fenarimol
- Flutamide
- Galeterone
- Guggulsterone
- Hydroxyflutamide
- Inocoterone
- Ketoconazole
- Lavender oil
- Linuron
- Megestrol acetate
- Mespirenone
- Methiocarb
- Metogest
- Mifepristone
- Nilutamide
- Nomegestrol
- Nordinone
- Norgestimate
- ODM-201
- ONC1-13B
- ORM-15341
- Osaterone
- Oxendolone
- PF-998425
- Potassium canrenoate
- Prochloraz
- Procymidone
- R-2956
- Rosterolone
- RU-58642
- RU-58841
- Spironolactone
- Topilutamide (fluridil)
- Topterone
- Valproic acid
- Vinclozolin
- VT-464
- Zanoterone
|
|
|
|
Enzyme |
Modulators
|
- See here instead (modulators of 20,22-desmolase, 17α-hydroxylase/17,20-lyase, 3β-HSD, 17β-HSD, 5α-reductase, and aromatase).
|
|
|
Others |
Precursors/prohormones
|
- Cholesterol
- 22R-Hydroxycholesterol
- 20α,22R-Dihydroxycholesterol
- Pregnenolone
- Pregnenolone sulfate
- 17-Hydroxypregnenolone
- Progesterone
- 17-Hydroxyprogesterone
- 11-Deoxycortisol (cortodoxone)
- DHEA
- DHEA sulfate
- Δ5-Androstenediol
- Δ4-Androstenedione
|
|
Indirect
|
- Antigonadotropins (e.g., estrogens, progestogens, prolactin)
- GnRH agonists (e,g, GnRH, leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Gonadotropins (e.g., FSH, hCG, LH)
- Kisspeptin
- Plasma proteins (ABP, albumin, SHBG)
|
|
|
See also: Estrogenics • Glucocorticoids • Mineralocorticoids • Progestogenics
|
|
Steroid hormone metabolism modulators
|
|
20,22-Desmolase |
- Inhibitors: 22-ABC
- 3,3′-Dimethoxybenzidine
- 3-Methoxybenzidine
- Aminoglutethimide
- Canrenone
- Cyanoketone
- Danazol
- Etomidate
- Ketoconazole
- Mitotane
- Spironolactone
- Trilostane
|
|
17α-Hydroxylase,
17,20-Lyase |
- Inhibitors: 22-ABC
- 22-Oxime
- Abiraterone
- Abiraterone acetate
- Bifonazole
- Canrenone
- CFG-920
- Clotrimazole
- Cyanoketone
- Cyproterone acetate
- Danazol
- Econazole
- Galeterone
- Gestrinone
- Isoconazole
- Ketoconazole
- L-39
- Liarozole
- LY-207,320
- MDL-27,302
- Miconazole
- Mifepristone
- Orteronel
- Pioglitazone
- Prochloraz
- Rosiglitazone
- Spironolactone
- Stanozolol
- SU-10,603
- TGF-β
- Tioconazole
- Troglitazone
- VN/87-1
- VT-464
- YM116
|
|
3α-HSD |
- Inhibitors: Coumestrol
- Daidzein
- Genistein
- Indomethacin
- Medroxyprogesterone acetate
- Inducers: Fluoxetine
- Fluvoxamine
- Mirtazapine
- Paroxetine
- Sertraline
- Venlafaxine
|
|
3β-HSD |
- Inhibitors: 4-MA
- Abiraterone
- Abiraterone acetate
- Azastene
- Cyanoketone
- Cyproterone acetate
- Danazol
- Epostane
- Genistein
- Gestrinone
- Metyrapone
- Norethisterone
- Oxymetholone
- Pioglitazone
- Rosiglitazone
- Trilostane
- Troglitazone
|
|
11β-HSD |
- Inhibitors: 18α-Glycyrrhizic acid
- ABT-384
- Acetoxolone
- Carbenoxolone
- Enoxolone (glycyrrhetinic acid)
- Epigallocatechin gallate
- Glycyrrhizin (glycyrrhizic acid)
|
|
21-Hydroxylase |
- Inhibitors: Aminoglutethimide
- Amphenone B
- Bifonazole
- Canrenone
- Clotrimazole
- Diazepam
- Econazole
- Genistein
- Isoconazole
- Ketoconazole
- Metyrapone
- Miconazole
- Midazolam
- Spironolactone
- Tioconazole
|
|
11β-Hydroxylase |
- Inhibitors: Abiraterone
- Abiraterone acetate
- Aminoglutethimide
- Canrenone
- Etomidate
- Fadrozole
- FETO
- Ketoconazole
- Metomidate
- Metyrapone
- Mitotane
- Potassium canrenoate
- Spironolactone
- Trilostane
|
|
18-Hydroxylase |
- Inhibitors: Aminoglutethimide
- Canrenone
- FAD286
- Fadrozole
- Ketoconazole
- LCI699
- Metyrapone
- Mespirenone
- Potassium canrenoate
- Spironolactone
|
|
17β-HSD |
- Inhibitors: Danazol
- Simvastatin
|
|
5α-Reductase |
- Inhibitors: 22-Oxime
- Alfatradiol
- Azelaic acid
- β-Sitosterol
- Bexlosteride
- Chlormadinone acetate
- Cl-4AS-1
- Dutasteride
- Epitestosterone
- Epristeride
- Fatty acids (α-linolenic acid, linoleic acid, γ-linolenic acid, monolinolein, oleic acid)
- Finasteride
- Ganoderic acid
- Izonsteride
- L-39
- Lapisteride
- Saw palmetto
- TFM-4AS-1
- Turosteride
- Vitamin B6
- Zinc
|
|
Aromatase |
- Inhibitors: 4-AT
- 4-Cyclohexylaniline
- 4-Hydroxytestosterone
- 5α-DHNET
- Abyssinone II
- Aminoglutethimide
- Anastrozole
- Ascorbic acid (vitamin C)
- Atamestane
- ATD
- Bifonazole
- CGP-45,688
- CGS-47,645
- Chalconoids (e.g., isoliquiritigenin)
- Corynesidone A
- Clotrimazole
- DHT
- Difeconazole
- Econazole
- Ellagitannins
- Endosulfan
- Exemestane
- Fadrozole
- Fatty acids (e.g., conjugated linoleic acid, linoleic acid, linolenic acid, palmitic acid)
- Fenarimol
- Finrozole
- Flavonoids (e.g., 7-hydroxyflavone, 7-hydroxyflavanone, 7,8-DHF, acacetin, apigenin, baicalein, biochanin A, chrysin, EGCG, gossypetin, hesperetin, liquiritigenin, myricetin, naringenin, pinocembrin, rotenone, quercetin, sakuranetin, tectochrysin)
- Formestane
- Imazalil
- Isoconazole
- Ketoconazole
- Letrozole
- Liarozole
- Melatonin
- MEN-11066
- Miconazole
- Minamestane
- Nimorazole
- NKS01
- Norendoxifen
- ORG-33,201
- Penconazole
- Phenytoin
- Prochloraz
- PGE2 (dinoprostone)
- Plomestane
- Prochloraz
- Propioconazole
- Pyridoglutethimide
- Quinolinoids (e.g., berberine, casimiroin, triptoquinone A, XHN22, XHN26, XHN27)
- Resorcylic acid lactones (e.g., zearalenone)
- Rogletimide
- Stilbenoids (e.g., resveratrol)
- Talarozole
- Terpenoids (e.g., dehydroabietic acid, (–)-dehydrololiolide, retinol (vitamin A), Δ9-THC, tretinoin)
- Testolactone
- Tioconazole
- Triadimefon
- Triadimenol
- Troglitazone
- Valproic acid
- Vorozole
- Xanthones (e.g., garcinone D, garcinone E, α-mangostin, γ-mangostin, monodictyochrome A, monodictyochrome B)
- YM-511
- Zinc
- Inducers: Atrazine
- Flavonoids (e.g., genistein, quercetin)
|
|
27-Hydroxylase |
- Inhibitors: Anastrozole
- Bicalutamide
- Dexmedetomidine
- Fadrozole
- Posaconazole
- Ravuconazole
|
|
See also: Androgenics • Estrogenics • Glucocorticoidics • Mineralocorticoidics • Progestogenics
|
|
Merck & Co., Inc.
|
|
Corporate directors: |
- Richard Clark
- Johnnetta Cole
- William Harrison
- William Kelley
- Rochelle Lazarus
- Thomas Shenk
- Anne Tatlock
- Samuel Thier
- Wendell Weeks
- Peter Wendell
|
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Products: |
- Alendronate
- Aprepitant
- Ertapenem
- Ezetimibe
- Ezetimibe/simvastatin
- Finasteride
- Fosaprepitant
- Indinavir
- Losartan
- Lovastatin
- Montelukast
- Omarigliptin
- Raltegravir
- Rizatriptan
- Rofecoxib
- Simvastatin
- Sitagliptin
- Vorinostat
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Publications: |
- The Merck Manuals
- Index
- Manual
- Veterinary
- Geriatrics
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