Finasteride
Clinical data | |
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Trade names | Proscar, Propecia, Finide, others |
Other names | MK-906; YM-152; L-652,931; 17β-(N-tert-Butylcarbamoyl)-4-aza-5α-androst-1-en-3-one; N-(1,1-Dimethylethyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide |
AHFS/Drugs.com | Monograph |
MedlinePlus | a698016 |
License data |
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Pregnancy category |
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Routes of administration | By mouth |
Drug class | 5α-Reductase inhibitor |
ATC code | |
Legal status | |
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Pharmacokinetic data | |
Bioavailability | 65%[5] |
Protein binding | 90%[5] |
Metabolism | Liver (CYP3A4, ALDH)[5] |
Elimination half-life | Adults: 5–6 hours[5] Elderly: >8 hours[5] |
Excretion | Feces: 57%[5] Urine: 40%[5] |
Identifiers | |
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Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men.[6] It can also be used to treat excessive hair growth in women.[7][8] It is usually taken orally but there are topical formulations for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles.[9]
Finasteride is a
In addition to DHT, finasteride also inhibits the production of several anticonvulsant neurosteroids including
Finasteride was patented in 1984 and approved for medical use in 1992.
Medical uses
Finasteride has been used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate[3] and for the treatment of male pattern hair loss (androgenetic alopecia) in men.[4]
Enlarged prostate
Physicians sometimes prescribe finasteride for the treatment of benign prostatic hyperplasia (BPH), informally known as an enlarged prostate.[21] Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up during the night to urinate, hesitation at the start and end of urination, and decreased urinary flow.[22]
The use of the drug showed significant sexual adverse effects such as erectile dysfunction and less sexual desire, in particular when obstructive symptoms due to an enlarged prostate were present.[23]
Scalp hair loss
Finasteride is also used to treat male pattern baldness (androgenic alopecia) in men, a condition that develops in up to 80% of Caucasian men aged 70 and over.[24][4] 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.[25] Treatment with finasteride slows further hair loss[26] and provides about 30% improvement in hair loss after six months of treatment, with effectiveness persisting as long as the drug is taken.[14] 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 crown but can reduce hair loss in all areas of the scalp.[27][28] Finasteride has also been tested for pattern hair loss in women; however, the results were no better than placebo.[29] Finasteride is less effective in the treatment of scalp hair loss than dutasteride.[30][31]
Prostate cancer
In males aged 55 years old and over finasteride decreases the risk of low-grade prostate cancer but may increase the risk of high-grade prostate cancer and has no effect on overall survival.[32]
A 2010 review found a 25% reduction in the risk of prostate cancer with 5α-reductase inhibitor.[33] A follow-up study of the Medicare claims of participants in a 10-year Prostate Cancer Prevention Trial suggests the reduction in prostate cancer is maintained even after discontinuation of treatment.[34] However, 5α-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.[35] No impact of 5-α-reductase inhibitor on survival has been found in people with prostate cancer.[35]
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.[7]
Transgender hormone therapy
Finasteride is sometimes used in
Adverse effects
A 2010 Cochrane review of finasteride for BPH found that, in men with a weighted mean age of 62.4, adverse effects are "rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo."[12] As of 2016[update] fresh evidence suggested such effects, along with disturbed neurosteroid production, may persist after finasteride use is stopped.[37]
Finasteride is contraindicated in pregnancy.[38][39] 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.[40]
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.[41][42] 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, though available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers.[4][43] A 2018 meta-analysis found no higher risk of breast cancer with 5α-reductase inhibitors.[44] Some men develop gynecomastia (breast development or enlargement) following finasteride usage.[45][46][47][48] The risk of gynecomastia with 5α-reductase inhibitors is low at about 1.5%.[49] Depressive symptoms and suicidality have been reported.[50]
Sexual adverse effects
Use of finasteride is associated with an increased risk of sexual dysfunction including erectile dysfunction, decreased libido and ejaculatory dysfunction.[51][13] Sexual adverse effects of finasteride and dutasteride have been linked to lower quality of life and ability to maintain an intimate relationship, and can cause stress in relationships.[52]
The adverse effect profiles of finasteride are somewhat different for its indications of hair loss and BPH.
Finasteride for androgenetic alopecia (hair loss in men)
The most common adverse effects of finasteride taken for hair loss are: decrease in sex drive, erectile dysfunction and decrease in amount of semen.[38]: 17
In addition, finasteride has been reported in
Finasteride for BPH
The most common adverse sexual effects of finasteride for BPH are: trouble getting or keeping an erection, decrease in sex drive, decreased volume of ejaculate and ejaculation disorders.[39]: 16
A 2010 Cochrane review found that men taking finasteride for BPH (with a mean age of 62.4) are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder for the first year of treatment. The rates became indistinguishable from placebo after 2–4 years and these side effects usually got better over time.[12]
Long-term
Finasteride may cause persistent adverse sexual, neurological and physical effects in a subset of men.[15] A 2019 metastudy surveyed the literature on the reversibility of finasteride's side effects. It identified three studies which demonstrated full reversibility of side effects and eleven that describe patients with irreversible adverse events. The findings were most convincing in a retrospective review of about 12,000 patients that 1.4% of the cohort developed persistent ED[15] (ED lasting longer than 90 days post-withdrawal).[54]
Post-finasteride syndrome
Reports of long-term, post-discontinuation adverse effects in some fraction of former finasteride users have led to a proposed post-finasteride syndrome, although some within the medical community question whether there is enough evidence to support a causal relationship between finasteride usage and PFS.[55]
Individuals claiming to experience PFS report sexual, neurological, hormonal and psychological side effects that persist for an extended period after stopping the drug.
The status of PFS as a legitimate and distinct medical pathology remains a subject of debate. A 2019 editorial in The BMJ called post-finasteride syndrome "ill defined and controversial".[59] Some have argued that it has common features with other self-diagnosed "mystery syndromes" such as Morgellons or multiple chemical sensitivity, while others, including some in the biomedical research community, have concluded based on the available evidence that it represents a real and serious condition.[16] There is no known underlying biological mechanism for the proposed syndrome, and its incidence is unclear.[60] A lack of clear diagnostic criteria and the variable reporting fraction in different health-care settings make the problem challenging to evaluate.[57]
As of 2016, Merck was a defendant in approximately 1,370 product liability lawsuits which had been filed by customers alleging they have experienced persistent sexual side effects following cessation of treatment with finasteride.[61] Most cases were settled by 2018 when Merck paid a lump sum of $4.3 million USD to be distributed. As of September 2019[update], 25 cases remained outstanding in the United States.[62] In 2019, Reuters reported that faulty redactions in court documents revealed allegations from plaintiffs that Merck had known of persistent side effects in their original clinical trials but chose not to disclose them in warning labels.[62]
Overdose
Finasteride has been studied in humans at single doses of up to 400 mg and at continuous dosages of up to 80 mg/day for three months, without adverse effects observed.[4][3][63] There is no specific recommended antidote for finasteride overdose.[4][3]
Interactions
No significant drug interactions have been observed between finasteride and a limited selection of medications.[64]
Pharmacology
Pharmacodynamics
Finasteride is a
Finasteride results in a decrease of circulating DHT levels by about 65–70% with an oral dosage of 5 mg/day and of DHT levels in the prostate gland by up to 80–90% with an oral dosage of 1 or 5 mg/day.
As of 2012, the tissues in which the different isozymes of 5α-reductase are expressed are not fully clear.
By inhibiting 5α-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.[77] Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.[78]
In accordance with finasteride being a potent 5α-reductase inhibitor but a weak inhibitor of 5β-reductase, the medication decreases circulating levels of 5α-reduced steroids like allopregnanolone but does not reduce concentrations of 5β-reduced steroids like pregnanolone.[82][83][84] Pregnanolone acts as a potent GABAA receptor positive allosteric modulator similarly to allopregnanolone.[85]
Pharmacokinetics
The mean
Finasteride is extensively
Chemistry
Finasteride, also known as 17β-(N-tert-butylcarbamoyl)-4-aza-5α-androst-1-en-3-one, is a
History
In 1942, James Hamilton observed that prepubertal castration prevents the later development of male pattern baldness in mature men.
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 had benign prostatic hyperplasia.[92]
Finasteride was developed by Merck under the code name MK-906.
Society and culture
Generic names
Finasteride is the
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
Athletics
From 2005 to 2009, the
Miscellaneous
The U.S. 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.[107] The UK also has a one-month deferral period.[108]
Research
Preliminary research suggests that topical finasteride may be effective in the treatment of pattern hair loss.[109][110] Topical finasteride, like the oral preparation, reduces serum DHT.[110][109]
DHT may be involved in the cause of
Androgens and estrogens may be involved in the cause of hidradenitis suppurativa (acne inversa).[114][115] Two case series have reported that finasteride is effective in the treatment of hidradenitis suppurativa in girls and women.[113]
Finasteride and other antiandrogens might be useful in the treatment of obsessive–compulsive disorder, but more research is needed.[116]
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