|Systematic (IUPAC) name|
|Trade names||Propecia, Proscar|
|Half-life||Elderly: 8 hours
Adults: 6 hours
|Excretion||Feces (57%) and urine (39%) as metabolites|
|ATC code||G04 D11|
|Mol. mass||372.549 g/mol|
|(what is this?)|
Finasteride (MK-906, Proscar, and Propecia by Merck, among other generic names) is a drug for the treatment of benign prostatic hyperplasia (BPH) and male pattern baldness (MPB). It is a type II 5α-reductase inhibitor; 5α-reductase, an enzyme, converts testosterone to dihydrotestosterone (DHT).
- 1 Medical 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
Benign prostatic hyperplasia
Physicians use finasteride for the treatment of 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.
Male pattern baldness
Finasteride is used to treat male pattern hair loss (androgenetic alopecia) in men only. Treatment provides about 30% improvement in hair loss after six months of treatment, and effectiveness only persists as long as the drug is taken.
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.
Side effects include increased risk of prostate cancer, reduced levels of prostate specific antigen (PSA) which could mask an increase in levels of PSA, which is used clinically a diagnostic test for prostate cancer, and sexual dysfunction. There may be a risk of breast cancer and mood disorders.
The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer. 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.
Sexual side effects
Two meta analyses have been conducted that explore the subject of sexual side effects caused by finasteride. One study found that active intervention with finasteride did not significantly differ from placebo in eliciting sexual dysfunction while the other suggested daily use of oral finasteride increase the risk of sexual dysfunction.
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. Nonetheless, a variety of small studies have suggested a possible connection.
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, 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 could not be excluded. Merck revised the United States' warning in consumer and medical leaflets to include the risk of male breast cancer.
Mechanism of action
Finasteride is a 5-alpha-reductase inhibitor, specifically the type II isoenzyme. By inhibiting 5a-reductase, finasteride prevents conversion of testosterone to dihydrotestosterone (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%, 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. In addition to blocking the type II isoenzyme, finasteride competitively inhibits the 5β-reductase type II isoenzyme, 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 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.
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.
Physical and chemical properties
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. Merck was awarded a separate patent for the use of finasteride to treat MPB. This patent expired in November 2013.
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.
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.
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.
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.
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. It was removed from the list effective January 1, 2009, after improvements in testing methods made the ban unnecessary. 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.
In 2012, an advocacy group called the Post-Finasteride Syndrome Foundation was formed; the group "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."
Finasteride has been clinically tested for baldness in women; the results were no better than placebo.
- Dutasteride, related 5α-reductase inhibitor (isozymes I, II, and III)
- Bexlosteride 5-α reductase inhibitor (isozyme I selective)
- Epristeride (SKF-105657) (SmithKline Beecham)
- Turosteride (FCE-26,073)
- 4-MA steroid not amp
- FCE 28260
- Izonsteride (LY-320,236)
- Lapisteride (INN; CS-891)
- Galeterone (TOK-001 or VN/124-1)
- Ganoderic acid
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- Proscar label
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- Primary Patent Expirations for Selected High Revenue Drugs
- fda.gov | Patent Expiration for Propecia
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