Jump to content

Finasteride: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Undid revision 625138860 by Formerly 98 (talk) Same as below, thanks
Undid revision 625138973 by Formerly 98 (talk) Same as below, thanks
Line 85: Line 85:
===Anxiety and depression===
===Anxiety and depression===
Mood disorders were not observed as an important adverse effect in the phase 3 trials leading to regulatory approval of finasteride for the treatment of benign prostatic hyperplasia.<ref name="Edwards JE, Moore RA 2002 14"/> Nonetheless, regulatory authorities have listed mood disorders as among the possible adverse effects of finasteride,<ref>{{cite journal |author=Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML |title=Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients |journal=The Journal of Sexual Medicine |volume=8 |issue=3 |pages=872–84 |date=March 2011 |pmid=21176115 |doi=10.1111/j.1743-6109.2010.02157.x |laysummary=http://abcnews.go.com/Health/MensHealth/baldness-drug-sexual-effects/story?id=13152993 |laysource=ABC News |laydate=March 16, 2011}}</ref> and a variety of small studies have suggested a possible connection.<ref name="pmid16834758">{{cite journal |author=Finn DA, Beadles-Bohling AS, Beckley EH, ''et al.'' |title=A new look at the 5alpha-reductase inhibitor finasteride |journal=CNS Drug Reviews |volume=12 |issue=1 |pages=53–76 |year=2006 |pmid=16834758 |doi=10.1111/j.1527-3458.2006.00053.x}}</ref>
Mood disorders were not observed as an important adverse effect in the phase 3 trials leading to regulatory approval of finasteride for the treatment of benign prostatic hyperplasia.<ref name="Edwards JE, Moore RA 2002 14"/> Nonetheless, regulatory authorities have listed mood disorders as among the possible adverse effects of finasteride,<ref>{{cite journal |author=Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML |title=Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients |journal=The Journal of Sexual Medicine |volume=8 |issue=3 |pages=872–84 |date=March 2011 |pmid=21176115 |doi=10.1111/j.1743-6109.2010.02157.x |laysummary=http://abcnews.go.com/Health/MensHealth/baldness-drug-sexual-effects/story?id=13152993 |laysource=ABC News |laydate=March 16, 2011}}</ref> and a variety of small studies have suggested a possible connection.<ref name="pmid16834758">{{cite journal |author=Finn DA, Beadles-Bohling AS, Beckley EH, ''et al.'' |title=A new look at the 5alpha-reductase inhibitor finasteride |journal=CNS Drug Reviews |volume=12 |issue=1 |pages=53–76 |year=2006 |pmid=16834758 |doi=10.1111/j.1527-3458.2006.00053.x}}</ref>

In a small study examining the use of finasteride to treat [[hirsutism]] in women, fewer patients in the finasteride-treated group reported depression relative to the control group.<ref>{{cite journal |author=Ciotta L, Cianci A, Calogero AE, ''et al.'' |title=Clinical and endocrine effects of finasteride, a 5 alpha-reductase inhibitor, in women with idiopathic hirsutism |journal=Fertility and Sterility |volume=64 |issue=2 |pages=299–306 |date=August 1995 |pmid=7615107}}</ref>

Another study with a larger sample size of 128 men, though no women, also at a dose of 1&nbsp;mg per day, found that finasteride increased both [[Beck Depression Inventory|BDI]] and [[Hospital Anxiety and Depression Scale|HADS]] depression scores significantly.<ref name="pmid17026771">{{cite journal |author=Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A |title=Finasteride induced depression: a prospective study |journal=BMC Clinical Pharmacology |volume=6 |issue= |pages=7 |year=2006 |pmid=17026771 |pmc=1622749 |doi=10.1186/1472-6904-6-7}}</ref> The authors concluded that finasteride should be prescribed cautiously to patients at a high risk of depression.

A study comparing depression in impotent men with a history of exposure to finasteride found that they experienced greater depression and suicidal ideation relative to non-impotent men without a history of finasteride exposure. The authors did not comment on the relative extent to which sexual dysfunction and prior finasteride treatment might have contributed to the depression.<ref name="Irwig MS 1220–3"/>


===Male breast cancer===
===Male breast cancer===

Revision as of 05:23, 28 September 2014

Finasteride
Clinical data
Trade namesPropecia, Proscar
AHFS/Drugs.comMonograph
MedlinePlusa698016
Pregnancy
category
  • X (will cause birth defects in a fetus)
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability63%
MetabolismHepatic
Elimination half-lifeElderly: 8 hours
Adults: 6 hours
ExcretionFeces (57%) and urine (39%) as metabolites
Identifiers
  • N-(1,1-dimethylethyl)-3-oxo-
    (5α,17β)-4-azaandrost-1-ene-17-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.149.445 Edit this at Wikidata
Chemical and physical data
FormulaC23H36N2O2
Molar mass372.549 g/mol g·mol−1
3D model (JSmol)
  • 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=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 checkY
  • Key:DBEPLOCGEIEOCV-WSBQPABSSA-N checkY
  (verify)

Finasteride (MK-906, Proscar and Propecia by Merck, among other generic names) is a synthetic drug for the treatment of benign prostatic hyperplasia (BPH) and male pattern baldness (MPB). It is a type II 5α-reductase inhibitor. 5α-reductase is an enzyme that converts testosterone to dihydrotestosterone (DHT).

Medical uses

Benign prostatic hyperplasia

Physicians use finasteride for the treatment of benign prostatic hyperplasia (BPH), informally known as an enlarged prostate. The FDA-approved dose is 5 mg once a day. Six months or more of treatment with finasteride may be required to determine the therapeutic results of treatment. If the drug is discontinued, any therapeutic benefits reverse within about 6–8 months. 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.[1]

Male pattern baldness

Three Phase 3 clinical trials examined the efficacy of finasteride in the treatment of mild to moderate male pattern baldness. The primary endpoints of each trial were hair count and user self-assessment. Secondary endpoints included investigator assessment and examination of scalp photographs. Each patient also filled out questionairres regarding sexual health and non-scalp body hair growth. These trials enrolled 1879 men and had a duration of one year.[2] Of these 1879 men, 1215 elected to participate in a one year double blind extension trial. Additional extension trials were performed such that 323 men experienced over 4 years of treatment.

Across all three trials, at one year men taking Propecia had 107 more hairs per 1 inch diameter section of scalp (in the area affected by hair loss) than men treated with placebo. At two years the difference was 138 hairs. Maximum hair gain occurred during the first two years, but because hair loss was more rapid in the placebo treated group, the difference between treated and placebo groups increased to 277 hairs per inch circle at 5 years.[3] Self assessment showed that treated patients perceived an improvement in hair density and overall appearance. These results were supported by investigator ratings and by independent readers examining scalp photographs.

At the end of the first year, the sexual health questionaire revealed differences in sexual interest, erections, and perception of sexual problems that favored the placebo group. However, no significant difference was seen in the question on overall satisfaction with sex life.[4]

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.[5][6] However, little clinical research of finasteride use for this purpose has been conducted and evidence of efficacy is limited. Indeed, finasteride is a substantially weaker antiandrogen in comparison to conventional antiandrogens like spironolactone and cyproterone acetate.

Adverse effects

In a four year controlled clinical study, 3040 patients with symptomatic benign prostatic hyperplasia were treated with 5 mg per day finasteride or placebo. Discontinuation rates due to adverse reactions related to sexual function were 3.7% in the finasteride arm and 2.1% in the placebo arm. Sexual effects were the most common type of adverse reaction.[7]

In 12 month duration double-blind clinical trials including more than 3000 patients, adverse effects included decreased libido (5% in the finasteride group and 3% in the placebo group), erectile dysfunction (8% finasteride, 3% placebo), and ejaculation disorder (2% finasteride, 0.6% placebo).[8]

Prostate cancer

The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer.[9] While the effect of finasteride on the risk of developing prostate cancer has not been established, evidence suggests it may temporarily reduce the growth and prevalence of benign prostate tumors, but could also mask the early detection of prostate cancer. The primary concern is patients who develop prostate cancer while taking finasteride 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.[10]

The 2005 Prostate Cancer Prevention Trial (PCPT) showed at a dosage of 5 mg per day, as is commonly prescribed for BPH, participants taking finasteride were 25% less likely to have developed prostate cancer at the end of the trial compared to those taking a placebo.[11] It appeared (incorrectly) that finasteride increased the specificity and selectivity of prostate cancer detection, thus creating an apparently increased rate of high Gleason grade tumor. A 2008 update of this study found that finasteride reduces the incidence of prostate cancer by 30%. In the original study, the smaller prostate caused by finasteride facilitated detection of cancer nests and aggressive-looking cells. Most of the men in the study who had both low and high-grade prostate cancer chose to be treated, and many had their prostates removed. A pathologist then carefully examined each of those 500 prostates and compared the kinds of cancers found at surgery to those initially diagnosed at biopsy. This study concluded that finasteride did not increase the risk of high-grade prostate cancer.[12][13]

Sexual side effects

There are case reports of persistent diminished libido or erectile dysfunction, even after stopping the drug.[14] In December 2008, the Swedish Medical Products agency concluded a safety investigation of finasteride and advised that finasteride may cause irreversible sexual dysfunction. The Agency's updated safety information lists difficulty in obtaining an erection that persists indefinitely, even after the discontinuation of finasteride, as a possible side effect of the drug.[15] The UK's Medical and Healthcare Products Regulatory Agency (MHRA) cites reports of erectile dysfunction that persists once use of finasteride has stopped.[citation needed][16] In April 2011 Merck revised the United States' warning in consumer and medical leaflets to include erectile dysfunction that may persist after stopping finasteride.[17] In April 2012, the warning label was further strengthened to include reports of persistent libido disorders, ejaculation disorders, orgasm disorders, and decreased libido. According to FDA, these warnings were added as precaution after reviewing 678 case reports of post-treatment sexual dysfunction received over an 18 year period. The Agency further stated that "despite the fact that clear causal links between finasteride (Propecia and Proscar) and sexual adverse events have NOT been established, the cases suggest a broader range of adverse effects than previously reported in patients taking these drugs.".[18][19][20]

Anxiety and depression

Mood disorders were not observed as an important adverse effect in the phase 3 trials leading to regulatory approval of finasteride for the treatment of benign prostatic hyperplasia.[8] Nonetheless, regulatory authorities have listed mood disorders as among the possible adverse effects of finasteride,[21] and a variety of small studies have suggested a possible connection.[22]

In a small study examining the use of finasteride to treat hirsutism in women, fewer patients in the finasteride-treated group reported depression relative to the control group.[23]

Another study with a larger sample size of 128 men, though no women, also at a dose of 1 mg per day, found that finasteride increased both BDI and HADS depression scores significantly.[24] The authors concluded that finasteride should be prescribed cautiously to patients at a high risk of depression.

A study comparing depression in impotent men with a history of exposure to finasteride found that they experienced greater depression and suicidal ideation relative to non-impotent men without a history of finasteride exposure. The authors did not comment on the relative extent to which sexual dysfunction and prior finasteride treatment might have contributed to the depression.[25]

Male breast cancer

In December 2009, the Medicines and Healthcare products Regulatory Agency in the UK announced new drug safety advice on finasteride and the potential risk of male breast cancer. The agency concluded that, although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not significantly increased, a higher risk of male breast cancer with finasteride use cannot be excluded. A warning on this risk will be included in the product information.[26] Merck revised the United States' warning in consumer and medical leaflets to include the risk of male breast cancer.[17]

Teratogenicity

Finasteride is in the FDA pregnancy category X. This means that it is known to cause birth defects in a fetus. Women who are or who may become pregnant must not handle crushed or broken finasteride tablets, because the medication could be absorbed through the skin. Finasteride is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed. It is not known whether finasteride passes into breast milk, and thus should not be taken by breastfeeding women. Finasteride may pass into the semen of men, but Merck states that a pregnant woman's contact with the semen of a man taking finasteride is not an issue for concern. Finasteride is known to affect blood donations, and potential donors are typically restricted for at least a month after their most recent dose.[27]

Interference with doping assays

Many sports organizations have banned finasteride because it can be used to mask steroid abuse.[28] Since 2005, finasteride has been on the World Anti-Doping Agency's list of banned substances. However, it was removed from the list in 2009.[29] 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.[30]

Mechanism of action

Testosterone in males is produced primarily in the testicles, but also in the adrenal glands. The majority of testosterone in the body is bound to sex hormone-binding globulin (SHBG), a protein produced in the liver that transports testosterone through the bloodstream, prevents its metabolism, and prolongs its half-life. Once it becomes unbound from SHBG, free testosterone can enter cells throughout the body. In certain tissues, notably the scalp, skin, and prostate, testosterone is converted into 5α-dihydrotestosterone (DHT) by the enzyme 5α-reductase. DHT is a more powerful androgen than testosterone (as it has approximately 3-10 times the potency at the androgen receptor, the site of action of the androgen hormones), so 5α-reductase can be thought to amplify the androgenic effect of testosterone in the tissues in which it's found.[citation needed]

Finasteride, a 4-azasteroid and analogue of testosterone, works by acting as a potent and specific, competitive inhibitor of one of the two subtypes of 5α-reductase, specifically the type II isoenzyme.[31] In other words, it binds to the enzyme and prevents endogenous substrates such as testosterone from being metabolized. 5α-reductase type I and type II are responsible for approximately one-third and two-thirds of systemic DHT production, respectively.[32]

Other 5a-reductase substrates include progesterone, androstenedione, epi-testosterone, cortisol, aldosterone, and deoxycorticosterone. The entire physiologic effect of their reduction is unknown, but likely related to their excretion or is itself physiologic. Beyond being a catalyst in the rate-limiting step in testosterone reduction, 5alpha-reductase enzyme isoforms I and II reduce progesterone to dihydroprogesterone (DHP) and deoxycorticosterone to dihydrodeoxycorticosterone (DHDOC). In vitro and animal models suggest subsequent 3alpha-reduction of DHT, DHP and DHDOC lead to steroid metabolites with effect on cerebral function by enhancing gamma-aminobutyric acid GABAergic inhibition. These neuroactive steroid derivatives enhance GABA at GABA(A) receptors and have anticonvulsant, antidepressant and anxiolytic effects, and also alter sexual and alcohol related behavior.[22] 5α-dihydrocortisol is present in the aqueous humor of the eye, is synthesized in the lens, and might help make the aqueous humor itself.[33] Allopregnanolone and THDOC are neurosteroids, with the latter having effects on the susceptibility of animals to seizures. 5α-dihydroaldosterone is a potent antidiuretic agent, although different from aldosterone. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium as follows:[34]

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

5α-DHP is a major hormone in circulation of normal cycling and pregnant women.[35]

By inhibiting 5a-reductase, finasteride prevents conversion of testosterone to DHT by the type II isoenzyme, resulting in a decrease in serum DHT levels by about 65–70% and in prostate DHT levels by up to 85–90%,[36] where expression of the type II isoenzyme dominates. Unlike dual inhibitors of both isoenzymes of 5α-reductase which can reduce DHT levels in the entire body by more than 99%, 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.[32] In addition to blocking the type II isoenzyme, finasteride competitively inhibits the 5β-reductase type II isoenzyme,[37] though this is not believed to affect androgen metabolism.

By blocking DHT production, finasteride reduces androgen activity in the scalp. In the prostate, inhibition of 5α-reductase reduces prostate volume, which improves benign prostatic hyperplasia (BPH) and reduces risk of prostate cancer. 5α-reductase inhibition also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.[38]

Vehicle

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.[39] Merck was awarded a separate patent for the use of finasteride to treat MPB. This patent is set to expire in November 2013.[40]

Finasteride is lipophilic,[41] and development of a liposomal system of finasteride for topical application has been a subject of recent study.[42] Topical formulations show some effect in reversal of androgenic effects on hair follicles,[43] as well as in hirsutism.[44] More recent studies have looked at microemulsions[41] and liquid crystalline nanoparticles for topical finasteride delivery. In the latter, addition of glycerol, propylene glycol, and polyethylene glycol 400, increased finasteride permeation, while addition of oleic acid made it decrease.[45] Topical finasteride in combination with topical minoxidil is more effective than topical minoxidil alone.[46] Small studies of topical finasteride formulations in combination with other drugs have also been found effective.[47] Surfactants have been shown to aid topical absorption.[48] Topical finasteride gel has been shown an effective route of administration.[49]

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 post-onset of puberty. Her research group found that 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.[50][51][52]

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 in order to treat older men who were suffering from benign prostatic hyperplasia.[53]

In 1992, finasteride (5 mg) was approved by the U.S. Food and Drug Administration (FDA) for treatment of benign prostatic hyperplasia (BPH), which Merck marketed under the brand name Proscar.

In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg) for treatment of male pattern baldness (MPB), which was marketed under the brand name Propecia.

See also

Epristeride 4-MA Turosteride Lapisteride Izonsteride
Epristeride
4-MA
Turosteride
Lapisteride
Izonsteride

The two isozymes, usually called Type I and Type II, exhibit differences in their biochemical properties, genetics and pharmacology. Both isozymes are now the subject of considerable research and it has been found that Type I is more prevalent in the scalp, and that Type II is more prevalent in the prostate.[54]

References

  1. ^ Edwards JE, Moore RA (December 2002). "Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials". BMC Urol. 2: 14. doi:10.1186/1471-2490-2-14. PMC 140032. PMID 12477383.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  2. ^ "www.accessdata.fda.gov" (PDF).
  3. ^ "www.accessdata.fda.gov" (PDF).
  4. ^ "www.accessdata.fda.gov" (PDF).
  5. ^ Gooren L (2005). "Hormone treatment of the adult transsexual patient". Hormone Research. 64 (Suppl 2): 31–6. doi:10.1159/000087751. PMID 16286768.
  6. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ "www.accessdata.fda.gov" (PDF).[full citation needed]
  8. ^ a b Edwards JE, Moore RA (December 2002). "Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials". BMC Urology. 2: 14. doi:10.1186/1471-2490-2-14. PMC 140032. PMID 12477383.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ 5α-reductase inhibitors (5-ARIs): Label Change – Increased Risk of Prostate Cancer | U.S. Department of Health & Human Services[full citation needed]
  10. ^ Walsh PC (April 2010). "Chemoprevention of prostate cancer". The New England Journal of Medicine. 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
  11. ^ "Can Prostate Cancer Be Prevented?". American Cancer Society. August 27, 2013. Retrieved September 3, 2013.
  12. ^ Gina Kolata (June 15, 2008). "New Take on a Prostate Drug, and a New Debate". NY Times. Retrieved 2008-06-15.
  13. ^ Redman MW, Tangen CM, Goodman PJ, Lucia MS, Coltman CA, Thompson IM (August 2008). "Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach". Cancer Prevention Research. 1 (3): 174–81. doi:10.1158/1940-6207.CAPR-08-0092. PMC 2844801. PMID 19138953.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Package Leaflet Information for the User, Swedish package insert for Propecia 1mg.
  16. ^ MHRA PUBLIC ASSESSMENT REPORT | The risk of male breast cancer with finasteride
  17. ^ a b PROPECIA® (finasteride) | Merck & Co., Inc.
  18. ^ <http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm299754.htm?utm_source=fdaSearch&utm_medium=website&utm_term=finasteride&utm_content=2>[full citation needed]
  19. ^ <http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/020180s039ltr.pdf>[full citation needed]
  20. ^ "FDA adds new side effects to finasteride label". Bloomberg Business Week. Associated Press. April 12, 2012. Retrieved September 3, 2014.
  21. ^ 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. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ a b 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  23. ^ Ciotta L, Cianci A, Calogero AE; et al. (August 1995). "Clinical and endocrine effects of finasteride, a 5 alpha-reductase inhibitor, in women with idiopathic hirsutism". Fertility and Sterility. 64 (2): 299–306. PMID 7615107. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  24. ^ Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A (2006). "Finasteride induced depression: a prospective study". BMC Clinical Pharmacology. 6: 7. doi:10.1186/1472-6904-6-7. PMC 1622749. PMID 17026771.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  25. ^ Cite error: The named reference Irwig MS 1220–3 was invoked but never defined (see the help page).
  26. ^ "MHRA drug safety advice: Finasteride and potential risk of male breast cancer". 4 December 2009. Retrieved 4 December 2009.
  27. ^ "FDA guidance on blood donors and medications" (PDF). U.S. Food and Drug Administration. Archived from the original (pdf) on October 31, 2005. Retrieved 01-02-2009. {{cite web}}: Check date values in: |accessdate= (help)
  28. ^ Sandomir, Richard (2006-01-19). "Skin Deep; Fighting Baldness, and Now an Olympic Ban". The New York Times. Retrieved 2010-05-02.
  29. ^ World Anti-Doping Agency Q&A: Status of Finasteride[dead link]
  30. ^ "Theodore's hair tonic causes positive test". TSN. 2006-02-10. Retrieved 2006-07-22.[dead link]
  31. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ a b "PROPECIA® (finasteride) Tablets, 1 mg [US/FDA label]" (PDF). Retrieved 2012-05-22.
  33. ^ Weinstein BI, Kandalaft N, Ritch R; et al. (June 1991). "5 alpha-dihydrocortisol in human aqueous humor and metabolism of cortisol by human lenses in vitro". Investigative Ophthalmology & Visual Science. 32 (7): 2130–5. PMID 2055703. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  34. ^ Kenyon CJ, Brem AS, McDermott MJ, Deconti GA, Latif SA, Morris DJ (May 1983). "Antinatriuretic and kaliuretic activities of the reduced derivatives of aldosterone". Endocrinology. 112 (5): 1852–6. doi:10.1210/endo-112-5-1852. PMID 6403339.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ Milewich L, Gomez-Sanchez C, Crowley G, Porter JC, Madden JD, MacDonald PC (October 1977). "Progesterone and 5alpha-pregnane-3,20-dione in peripheral blood of normal young women: Daily measurements throughout the menstrual cycle". The Journal of Clinical Endocrinology and Metabolism. 45 (4): 617–22. doi:10.1210/jcem-45-4-617. PMID 914969.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  36. ^ 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:10.1007/s00345-002-0248-5. PMID 10765065.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  38. ^ 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.
  39. ^ Primary Patent Expirations for Selected High Revenue Drugs
  40. ^ fda.gov | Patent Expiration for Propecia
  41. ^ a b 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Kumar R, Singh B, Bakshi G, Katare OP (2007). "Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation". Pharmaceutical Development and Technology. 12 (6): 591–601. doi:10.1080/10837450701481181. PMID 18161632.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  43. ^ Ye F, Imamura K, Imanishi N, Rhodes L, Uno H (1997). "Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats". Skin Pharmacology. 10 (5–6): 288–97. PMID 9449168.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  44. ^ Póltorak JL (January 1976). "[Bile duct calculosis]". Polski Tygodnik Lekarski (in Polish). 31 (4): 145–8. PMID 1250761.
  45. ^ Madheswaran T, Baskaran R, Thapa RK; et al. (March 2013). "Design and in vitro evaluation of finasteride-loaded liquid crystalline nanoparticles for topical delivery". AAPS PharmSciTech. 14 (1): 45–52. doi:10.1208/s12249-012-9888-y. PMC 3581658. PMID 23207960. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  46. ^ Tanglertsampan C (October 2012). "Efficacy and safety of 3% minoxidil versus combined 3% minoxidil / 0.1% finasteride in male pattern hair loss: a randomized, double-blind, comparative study". Journal of the Medical Association of Thailand. 95 (10): 1312–6. PMID 23193746.
  47. ^ Rafi AW, Katz RM (2011). "Pilot Study of 15 Patients Receiving a New Treatment Regimen for Androgenic Alopecia: The Effects of Atopy on AGA". ISRN Dermatology. 2011: 241953. doi:10.5402/2011/241953. PMC 3262531. PMID 22363845.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  48. ^ Javadzadeh Y, Shokri J, Hallaj-Nezhadi S, Hamishehkar H, Nokhodchi A (December 2010). "Enhancement of percutaneous absorption of finasteride by cosolvents, cosurfactant and surfactants". Pharmaceutical Development and Technology. 15 (6): 619–25. doi:10.3109/10837450903397610. PMID 19929166.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  49. ^ Hajheydari Z, Akbari J, Saeedi M, Shokoohi L (2009). "Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia". Indian Journal of Dermatology, Venereology and Leprology. 75 (1): 47–51. PMID 19172031.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  50. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  51. ^ 5-Alpha-Reductase Deficiency | WebMD
  52. ^ Dutasteride | Clinical Trials | International Society of Hair Restoration Surgery
  53. ^ Freudenheim, Milt (February 16, 1992). "Keeping the Pipeline Filled at Merck". The New York Times.
  54. ^ U.S. patent 5,629,007

Template:Depressogenics

Retrieved from "https://en.wikipedia.org/w/index.php?title=Finasteride&oldid=627377088"