Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used mainly to treat an enlarged prostate or scalp hair loss in men. It can also be used to treat excessive hair growth in women and as a part of hormone therapy for transgender women. It is taken by mouth.
Side effects are generally mild. It increases the risk of certain rare forms of prostate cancer, and some men may experience sexual dysfunction, depression, anxiety, or breast enlargement. Finasteride is a 5?-reductase inhibitor, and hence is an antiandrogen. It works by decreasing the production of dihydrotestosterone (DHT), an androgen sex hormone, in certain parts of the body like the prostate gland and the scalp. It inhibits two of the three forms of 5?-reductase, and can decrease DHT levels in the blood by up to 70%.
Finasteride was introduced for the treatment of prostate enlargement in 1992 and was approved for the treatment of scalp hair loss in 1997. It was the first 5?-reductase inhibitor to be introduced and was followed by dutasteride a number of years later. The drug is available as a generic medication.
Video Finasteride
Medical uses
Prostate enlargement
Physicians sometimes prescribe finasteride for the treatment of benign prostatic hyperplasia (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 cm3. 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.
Prostate cancer
A 2010 Cochrane review found a 25-26% reduction in the risk of developing prostate cancer with 5?-reductase inhibitor chemoprevention. A followup study of the Medicare claims of participants in a 10-year Prostate Cancer Prevention Trial suggests a significant reduction in prostate cancer risk is maintained even after discontinuation of treatment. However, 5?-reductase inhibitors have been found to increase the risk of developing certain rare but aggressive forms of prostate cancer (27% risk increase), although not all studies have observed this.
Scalp hair loss
Finasteride is also used to treat pattern hair loss (androgenetic alopecia) in men, a condition that develops in up to 80% of Caucasian men. In the United States, finasteride and minoxidil are the only two FDA approved drugs for the treatment of male pattern hair loss as of 2017. Treatment with finasteride slows further hair loss and provides about 30% improvement in hair loss after six months of treatment, with effectiveness persisting as long as the drug is taken. Taking finasteride leads to a reduction in scalp and serum DHT levels; by lowering scalp levels of DHT, finasteride can maintain or increase the amount of terminal hairs in the anagen phase by inhibiting and sometimes reversing miniaturization of the hair follicle. Finasteride is most effective on the vertex but can reduce hair loss in all areas of the scalp. Finasteride has also been tested for pattern hair loss in women; however, the results were no better than placebo.
Excessive hair growth
Finasteride has been found to be effective in the treatment of hirsutism (excessive facial and/or body hair growth) in women. In a study of 89 women with hyperandrogenism due to persistent adrenarche syndrome, finasteride produced a 93% reduction in facial hirsutism and a 73% reduction bodily hirsutism after 2 years of treatment. Other studies using finasteride for hirsutism have also found it to be clearly effective.
Transgender women
Finasteride is sometimes used in hormone replacement therapy for transgender women due to its antiandrogenic effects, in combination with a form of estrogen. However, little clinical research of finasteride use for this purpose has been conducted and evidence of safety or efficacy is limited. Moreover, caution has been recommended when prescribing finasteride to transgender women, as finasteride may be associated with side effects such as depression, anxiety, and suicidal ideation, symptoms that are particularly prevalent in the transgender population and in others at high risk already.
Maps Finasteride
Contraindications
Finasteride may cause birth defects in a male fetus if a pregnant woman takes finasteride or is exposed to finasteride pill fragments. It is classified in the FDA pregnancy category X.
Adverse effects
A 2010 Cochrane review concluded that adverse effects from finasteride are rare when used for BPH.
The FDA has added a warning to 5?-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. 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.
Some men develop breast enlargement (gynecomastia) following finasteride usage. It may increase the risk of insulin resistance and diabetes mellitus type 2 and also of osteoporosis.
A 2015 review found that none of the clinical trials of finasteride in hair loss had adequate safety reporting. Moreover, the trials submitted to the FDA for approval for hair loss excluded most men who are typically prescribed finasteride for androgenic alopecia.
Sexual dysfunction
Finasteride causes short-term sexual dysfunction in some men. A 2017 analysis of clinical trial data in men with BPH treated with finasteride found an odds ratio of 1:45 for erectile dysfunction and a 1:54 odds ratio for decreased libido; both odds ratios decreased for longer trials.
Whether finasteride causes long-term sexual dysfunction in some men after stopping drug treatment is unclear. There are case reports of persistent diminished libido or erectile dysfunction after stopping the drug and the FDA has updated the label to inform people of these reports. 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. In many people these side effects resolve if the medication is stopped and occasionally resolve even if the medication is continued. They additionally state "the sexual functioning questionnaire seems to have given a sensitive reflection of the disturbance on sexual functioning".
The 2010 Cochrane review found that compared with placebo, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder for the first year of treatment; the rates of these effects became indistinguishable from placebo after 2-4 years and these side effects usually got better over time. Another 2010 review found that when used for hair loss finasteride increased rates of sexual problems. A 2016 review of 5?-reductase inhibitors for prostatic hyperplasia found that sexual dysfunction was 2.5 times more likely in those who used them. Another 2016 review, a meta-analysis found that sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride. This adverse effect has been linked to lower quality of life and can cause stress in relationships. There is also an association with lowered sexual desire. It has been reported that in a subset of men, these adverse sexual side effects may persist even after discontinuation of finasteride or dutasteride.
In men with prostatic hyperplasia the use of both a 5?-reductase inhibitor and a ?1-adrenergic receptor blocker resulted in a greater risk of erectile dysfunction compared to either agent alone.
Pharmacology
Pharmacodynamics
Finasteride is a 5?-reductase inhibitor. It is specifically a selective inhibitor of the type II and III isoforms of the enzyme. By inhibiting these two isozymes of 5?-reductase, finasteride reduces the formation of the potent androgen dihydrotestosterone (DHT) from its precursor testosterone in certain tissues in the body such as the prostate gland, skin, and hair follicles. As such, finasteride is a type of antiandrogen, or more specifically, an androgen synthesis inhibitor.
Finasteride results in a decrease of circulating DHT levels by about 65 to 70% with an oral dose of 5 mg and of DHT levels in the prostate gland by up to 80 to 90% with an oral dose of 1 or 5 mg. Unlike inhibitors of all three isoenzymes of 5?-reductase like dutasteride, 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 5?-reductase type I isoenzyme, with more than 100-fold less inhibitory potency for type I as compared to type II (IC50 = 313 nM and 11 nM, respectively). In addition to inhibiting 5?-reductase, finasteride has also been found to competitively inhibit 5?-reductase (AKR1D1), although its affinity for the enzyme is substantially less than for 5?-reductase (an order of magnitude less than 5?-reductase type I) and hence is unlikely to be of clinical significance. As of 2012, the tissues in which the different isozymes of 5?-reductase are expressed are not fully clear, as different investigators have obtained varying results with different reagents, methods, and tissues examined. However, the different isozymes appear to be widely expressed, most notably in the prostate gland and hair follicles.
By inhibiting 5?-reductase and thus preventing DHT production, finasteride reduces androgen signaling in tissues like the prostate gland and the scalp. In the prostate, this reduces prostate volume, which improves BPH and reduces risk of prostate cancer. Finasteride reduces prostate volume by 20 to 30% in men with benign prostatic hyperplasia. Inhibition of 5?-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis. Neurosteroids like 3?-androstanediol and allopregnanolone activate the GABAA receptor in the brain; because finasteride prevents the formation of neurosteroids, it may contribute to a reduction of GABAA activity (see also neurosteroidogenesis inhibitor). Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression, anxiety, and sexual dysfunction.
Pharmacokinetics
The mean oral bioavailability of finasteride is approximately 65%. Its volume of distribution is 76 L/kg. The plasma protein binding of finasteride is 90%. The drug has been found to cross the blood-brain barrier, whereas levels in semen were found to be undetectable. Finasteride is extensively metabolized in the liver, first by hydroxylation via CYP3A4 and then by aldehyde dehydrogenase. The metabolites of finasteride have about 20% of its potency in inhibiting 5?-reductase and hence its metabolites are not particularly active. The drug has a terminal half-life of 5 to 6 hours in adult men (18-60 years of age) and a terminal half-life of 8 hours or more in elderly men (greater than 70 years of age). It is eliminated as its metabolites 57% in the feces and 40% in the urine.
Chemistry
Finasteride, also known as 17?-(N-tert-butylcarbamoyl)-4-aza-5?-androst-1-en-3-one, is a synthetic androstane steroid and 4-azasteroid. It is an analogue of androgen steroid hormones like testosterone and DHT. As an unconjugated steroid, finasteride is a highly lipophilic compound.
History
In 1942, James Hamilton observed that prepubertal castration prevents the later development of male pattern baldness in mature men. 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 5?-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.
Finasteride was developed under the code name MK-906. 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
Generic names
Finasteride is the generic name of the drug and its INN, USAN, BAN, and JAN, while finastéride is its DCF. It is also known by its former developmental code names MK-906, YM-152, and L-652,931.
Brand names
Finasteride is marketed primarily under the brand names Propecia, for pattern hair loss, and Proscar, for BPH, both of which 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 pattern hair loss. This patent expired in November 2013. Finasteride is also marketed under a variety of other brand names throughout the world.
Controversy
Men in the U.S. and Canada concerned about persistent sexual side effects "coined the phrase 'post-finasteride syndrome', which they say is characterized by sexual, neurological, hormonal and psychological side effects that can persist in men who have taken finasteride for hair loss or an enlarged prostate". 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. A 2015 post in Health News Review noted that the foundation put out a press release timed to the publication of a review it had funded; the post said that the release "seems rather hyperbolic in admonishing physicians to be vigilantly looking out for "symptoms in adverse drug reaction reports, suicide post-mortems, suicide-prevention services, and other patient records" and to alert the general population.... These appeals strike me as uncomfortably reminiscent of late-night TV and billboard pitches for malpractice attorneys." The release claimed that the NIH had "recognized" "post-finasteride syndrome"; in response to an inquiry an NIH spokeswoman said: "The statement by the Post Finasteride Foundation you referenced therefore is not accurate and was not determined by us."
According to the company's 1Q2016 financial filing, Merck is a defendant in 1,385 product liability lawsuits which have been filed by customers alleging they have experienced persistent sexual side effects following cessation of treatment with finasteride.
Athletics
From 2005 to 2009, the World Anti-Doping Agency banned finasteride because it was discovered that 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. Athletes who used finasteride and were banned from international competition include skeleton racer Zach Lund, bobsledder Sebastien Gattuso, footballer Romário and ice hockey goaltender José Théodore.
Miscellaneous
The Food and Drug Administration advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride.
Harold Bornstein, the personal physician of United States President Donald Trump, stated that Trump was taking finasteride to promote hair growth.
References
Source of article : Wikipedia
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