Finasteride
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Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat
hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...
and
benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
(BPH) in men. It can also be used to treat excessive hair growth in women and as a part of
hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...
for
transgender women A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and som ...
. It is taken
by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...
. Finasteride is a
5α-reductase inhibitor 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...
and therefore an
antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
. It works by decreasing the
production Production may refer to: Economics and business * Production (economics) * Production, the act of manufacturing goods * Production, in the outline of industrial organization, the act of making products (goods and services) * Production as a stati ...
of
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...
(DHT) by about 70%, including in the
prostate gland The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physio ...
and the
scalp The scalp is the anatomical area bordered by the human face at the front, and by the neck at the sides and back. Structure The scalp is usually described as having five layers, which can conveniently be remembered as a mnemonic: * S: The ski ...
. In addition to DHT, finasteride also inhibits the production of several anticonvulsant neurosteroids including allopregnanolone,
androstanediol Androstanediol may refer to: * 3α-Androstanediol (5α-androstane-3α,17β-diol) – an endogenous neurosteroid, weak androgen and estrogen, and intermediate to androsterone * 3β-Androstanediol (5α-androstane-3β,17β-diol) – an endogenous es ...
, and
THDOC Tetrahydrodeoxycorticosterone (abbreviated as THDOC; 3α,21-dihydroxy-5α-pregnan-20-one), also referred to as ''allotetrahydrocorticosterone'', is an endogenous neurosteroid. It is synthesized from the adrenal hormone deoxycorticosterone by t ...
.
Adverse effects An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...
from finasteride are rare, however some men experience
sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as ...
, depression, and
breast enlargement Breast enlargement is the enlargement of the breasts. It may occur naturally as in mammoplasia or may occur artificially through active intervention. Many women regard their breasts, which are female secondary sex characteristics, as important to t ...
. In some men, sexual dysfunction may persist after stopping the medication. It may also hide the early symptoms of certain forms of
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
. Finasteride was patented in 1984 and approved for medical use in 1992. It is available as a
generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. In 2020, it was the 90th most commonly prescribed medication in the United States, with more than 8million prescriptions.


Medical uses

Finasteride has been used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate and for the treatment of male pattern hair loss (androgenetic alopecia) in men.


Enlarged prostate

Physicians sometimes prescribe finasteride for the treatment of benign prostatic hyperplasia (BPH), informally known as an enlarged
prostate The prostate is both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...
. 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. 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.


Scalp hair loss

Finasteride is also used to treat
male pattern baldness Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...
(androgenic alopecia) in men, a condition that develops in up to 80% of Caucasian men. In the United States, finasteride and
minoxidil Minoxidil, sold under the brand name Rogaine among others, is a medication used for the treatment of high blood pressure and pattern hair loss. It is an antihypertensive vasodilator. It is available as a generic medication by prescription in or ...
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
crown A crown is a traditional form of head adornment, or hat, worn by monarchs as a symbol of their power and dignity. A crown is often, by extension, a symbol of the monarch's government or items endorsed by it. The word itself is used, partic ...
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. Finasteride is less effective in the treatment of scalp hair loss than
dutasteride Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefi ...
.


Prostate cancer

In males over 55 years old finasteride decreases the risk of low-grade
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
but may increase the risk of high-grade prostate cancer and has no effect on overall survival. A 2010 review found a 25% reduction in the risk of prostate cancer with 5α-reductase inhibitor. 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. 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. No impact of 5-α-reductase inhibitor on survival has been found in people with prostate cancer.


Excessive hair growth

Finasteride has been found to be effective in the treatment of
hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
(excessive facial and/or body hair growth) in women. In a study of 89 women with
hyperandrogenism Hyperandrogenism is a medical condition characterized by high levels of androgens. It is more common in women than men. Symptoms of hyperandrogenism may include acne, seborrhea (inflamed skin), hair loss on the scalp, increased body or facia ...
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 hormone therapy

Finasteride is sometimes used in
hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...
for
transgender women A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and som ...
due to its
antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
ic effects, in combination with a form of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
. However, little
clinical research Clinical research is a branch of healthcare science that determines the safety and effectiveness ( efficacy) of medications, devices, diagnostic products and treatment regimens intended for human use. These may be used for prevention, treatm ...
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.


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." fresh evidence suggested such effects, along with disturbed neurosteroid production, may persist after finasteride use is stopped. Finasteride is contraindicated in pregnancy. The
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride. The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
, as the treatment of BPH lowers PSA (
prostate-specific antigen Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the ''KLK3'' gene. PSA is a member of the kallikrein-related peptidase family and is secreted b ...
), 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, though available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers. A 2018
meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
found no higher risk of breast cancer with 5α-reductase inhibitors. Some men develop
gynecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...
(breast development or enlargement) following finasteride usage. The risk of gynecomastia with 5α-reductase inhibitors is low at about 1.5%. Depressive symptoms and suicidality have been reported.


Sexual adverse effects

Use of finasteride is associated with an increased risk of
sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as ...
including
erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...
, decreased libido and ejaculatory dysfunction. Sexual adverse effects of finasteride and dutasteride have been linked to lower
quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
and ability to maintain an intimate relationship, and can cause stress in relationships. 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. In addition, finasteride has been reported in
case reports In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrence ...
to cause sexual problems which persist after stopping the medication. A 2012 update to the FDA label noted reports of decreased sex drive, problems with ejaculation and difficulty achieving an erection which continued after stopping the medication. The update also referenced reports of testicular pain and "male infertility and/or poor quality of semen."


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. 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.


Long-term

Finasteride may cause persistent adverse sexual, neurological and physical effects in a subset of men. 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 (ED lasting longer than 90 days post-withdrawal).


Post-finasteride syndrome

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". As of 2016, Merck was a defendant in approximately 1,370
product liability Product liability is the area of law in which manufacturers, distributors, suppliers, retailers, and others who make products available to the public are held responsible for the injuries those products cause. Although the word "product" has br ...
lawsuits which had been filed by customers alleging they have experienced persistent sexual side effects following cessation of treatment with finasteride. A 2019 editorial in ''
The BMJ ''The BMJ'' is a weekly peer-reviewed medical trade journal, published by the trade union the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world's oldest general medical journals. Origi ...
'' called post finasteride syndrome "ill defined and controversial". Some have argued that it has common features with other self-diagnosed "mystery syndromes" such as morgellons syndrome or
multiple chemical sensitivity Multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerances (IEI), is an unrecognized and controversial diagnosis characterized by chronic symptoms attributed to exposure to low levels of commonly used chemicals. Symp ...
, while others argue "that finasteride and
dutasteride Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefi ...
induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men" which "constitute the basis for PFS". There is no known underlying biological mechanism for the proposed syndrome, and its incidence is also unclear. A lack of clear diagnostic criteria and the variable reporting fraction in different health-care settings make the problem challenging to evaluate. Self-reported symptoms of post-finasteride syndrome include penile
atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
and tissue changes, decreased ejaculate volume and quality, libido loss, erectile dysfunction, loss of penile sensitivity, decreased orgasm sensation, dry skin, metabolic changes, muscle and strength loss,
gynecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...
, depression, anxiety, panic attacks, insomnia,
anhedonia Anhedonia is a diverse array of deficits in hedonic function, including reduced motivation or ability to experience pleasure. While earlier definitions emphasized the inability to experience pleasure, anhedonia is currently used by researchers t ...
, concentration problems, memory impairment and
suicidal ideation Suicidal ideation, or suicidal thoughts, means having thoughts, ideas, or ruminations about the possibility of ending one's own life.World Health Organization, ''ICD-11 for Mortality and Morbidity Statistics'', ver. 09/2020MB26.A Suicidal ideatio ...
. A meta-analysis found significant association between finasteride use and post-discontinuation depression, suicide ideation, and sexual dysfunction, but the quality of evidence was limited. Plaintiffs have filed over one thousand court cases against Merck over the effects of finasteride. Most were settled by 2018 when Merck paid a lump sum of US$4.3 million to be distributed. , 25 cases remained outstanding in the United States. 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.


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. There is no specific recommended
antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...
for finasteride overdose.


Interactions

No significant
drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...
s have been observed between finasteride and a limited selection of medications.


Pharmacology


Pharmacodynamics

Finasteride is a
5α-reductase inhibitor 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...
. It is specifically a selective inhibitor of the type II and III
isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
s of the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
. By inhibiting these two isozymes of 5α-reductase, finasteride reduces the formation of the potent
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...
(DHT) from its
precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
in certain tissues in the body such as the
prostate gland The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physio ...
,
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
, and
hair follicle The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between h ...
s. As such, finasteride is a type of
antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
, or more specifically, an
androgen synthesis inhibitor An androgen synthesis inhibitor is a type of drug which inhibits the enzymatic synthesis of androgens, such as testosterone and dihydrotestosterone (DHT). They include: * CYP17A1 inhibitors (17α-hydroxylase/17,20-lyase inhibitors): inhibit the s ...
. However, some authors do not define finasteride as an "antiandrogen," a term which can refer more specifically to antagonists of the
androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
. Finasteride results in a decrease of circulating DHT levels by about 65 to 70% with an oral dosage of 5 mg/day and of DHT levels in the prostate gland by up to 80 to 90% with an oral dosage of 1 or 5 mg/day. In parallel, circulating levels of testosterone increase by approximately 10%, while local concentrations of testosterone in the prostate gland increase by about 7-fold and local testosterone levels in hair follicles increase by around 27 to 53%. An oral dosage of finasteride of only 0.2 mg/day has been found to achieve near-maximal suppression of DHT levels (68.6% for 0.2 mg/day relative to 72.2% for 5 mg/day). Finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the 5α-reductase type I isoenzyme, with more than 100-fold less inhibitory potency for type I as compared to type II ( = 313 nM and 11 nM, respectively). This is in contrast to inhibitors of all three isoenzymes of 5α-reductase like
dutasteride Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefi ...
, which can reduce DHT levels in the entire body by more than 99%. In addition to inhibiting 5α-reductase, finasteride has also been found to competitively inhibit 5β-reductase (AKR1D1). However, its affinity for the enzyme is substantially less than for 5α-reductase (an order of magnitude less than for 5α-reductase ''type I'') and hence is unlikely to be of clinical significance. As of 2012, the tissues in which the different isozymes of 5α-reductase are expressed are not fully clear. This is because different investigators have obtained varying results with different
reagent In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
s, methods, and tissues examined. However, the different isozymes of 5α-reductase appear to be widely expressed, with notable tissues including the prostate gland,
seminal vesicle The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen. The vesicles are 5 ...
s,
testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
, epididymides, skin, hair follicles,
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
,
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s, and
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
, among others. 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. Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis. Neurosteroids like 3α-androstanediol (derived from DHT) and allopregnanolone (derived from
progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
) activate the GABAA receptor in the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
; because finasteride prevents the formation of neurosteroids, it functions as a neurosteroidogenesis inhibitor and may contribute to a reduction of GABAA activity. Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression,
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, and
sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as ...
. 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. Pregnanolone acts as a potent GABAA receptor positive allosteric modulator similarly to allopregnanolone.


Pharmacokinetics

The mean
oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or or ...
bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
of finasteride is approximately 65%. The
absorption Absorption may refer to: Chemistry and biology * Absorption (biology), digestion **Absorption (small intestine) *Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials *Absorption (skin), a route by which ...
of finasteride is not affected by food. At
steady-state In systems theory, a system or a process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties ''p'' ...
with 1 mg/day finasteride, mean
peak Peak or The Peak may refer to: Basic meanings Geology * Mountain peak ** Pyramidal peak, a mountaintop that has been sculpted by erosion to form a point Mathematics * Peak hour or rush hour, in traffic congestion * Peak (geometry), an (''n''-3)-di ...
concentrations of finasteride were 9.2 ng/mL (25 nmol/L). Conversely, following a single 5 mg dose of finasteride, mean peak levels of finasteride were 37 ng/mL (99 nmol/L), and plasma concentrations increased by 47 to 54% following 2.5 weeks of continued daily administration. The
volume of distribution In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same c ...
of finasteride is 76 L. Its
plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...
is 90%. The drug has been found to cross the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
, whereas levels in
semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Semen i ...
were found to be undetectable. Finasteride is extensively
metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
in the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, first by
hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...
via
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
and then by
aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...
. It has two major
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s, which are the ''tert''-
butyl In organic chemistry, butyl is a four- carbon alkyl radical or substituent group with general chemical formula , derived from either of the two isomers (''n''-butane and isobutane) of butane. The isomer ''n''-butane can connect in two ways, gi ...
side chain In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a l ...
monohydroxylated and monocarboxylic acid metabolites. These metabolites show approximately 20% of the inhibitory activity of finasteride on 5α-reductase. Hence, the metabolites of finasteride are not particularly active. The drug has a
terminal half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
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 (more than 70 years of age). It is eliminated as its metabolites 57% in the
feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...
and 40% in the
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...
.


Chemistry

Finasteride, also known as 17β-(''N''-tert-butylcarbamoyl)-4-aza-5α-androst-1-en-3-one, is a synthetic
androstane Androstane is a C19 steroidal hydrocarbon with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacology ...
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
and 4-azasteroid. It is an analogue of androgen
steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...
s like testosterone and DHT. As an unconjugated steroid, finasteride is a highly
lipophilic Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...
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 Intersex people are individuals born with any of several sex characteristics including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical bina ...
children in the
Caribbean The Caribbean (, ) ( es, El Caribe; french: la Caraïbe; ht, Karayib; nl, De Caraïben) is a region of the Americas that consists of the Caribbean Sea, its islands (some surrounded by the Caribbean Sea and some bordering both the Caribbean Se ...
who appeared sexually
ambiguous Ambiguity is the type of meaning (linguistics), meaning in which a phrase, statement or resolution is not explicitly defined, making several interpretations wikt:plausible#Adjective, plausible. A common aspect of ambiguity is uncertainty. It ...
at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic after onset of puberty. These children, despite being raised as girls until puberty, were generally heterosexual, and were termed " Guevedoces" by their local community, which means "penis at twelve" in Spanish. Her research group found these children shared a
genetic mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
, causing deficiency of the 5α-reductase enzyme and male hormone
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...
(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 Pindaros Roy Vagelos (born October 8, 1929, in Westfield, New Jersey), better known as P. Roy Vagelos or Roy Vagelos, is an American physician and business executive, who was president and chief executive officer (1985) and chairman (1986) of t ...
, who was then serving as
Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...
'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. Finasteride was developed by Merck under the code name MK-906. A team led by chemist Gary Rasmusson and biologist Jerry Brooks developed potential 5α-reductase inhibitors based on transition state inhibitors, using an iterative process of molecular design, testing, and redesign. In 1992, finasteride (5 mg) was approved by the
U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) for treatment of BPH, which Merck marketed under the brand name Proscar. Rasmusson and Brooks were awarded IPO's "Inventor of the Year" award in 1993 for their work on finasteride. In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg) for treatment of male pattern hair loss, which was marketed under the brand name Propecia. It was the first 5α-reductase inhibitor to be introduced and was followed by
dutasteride Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefi ...
in 2001. The first study of finasteride in the treatment of hirsutism in women was published in 1994.


Society and culture


Generic names

''Finasteride'' is the generic name of the drug and its , , , and , while ''finastéride'' is its . 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 Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp ...
. There is 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck's patent on finasteride for the treatment of BPH expired in June 2006. Merck was awarded a separate patent for the use of finasteride to treat pattern hair loss and it expired in November 2013. Finasteride is also marketed under a variety of other brand names throughout the world.


Athletics

From 2005 to 2009, the
World Anti-Doping Agency The World Anti-Doping Agency (WADA; french: Agence mondiale antidopage, AMA) is a foundation initiated by the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against drugs in sports. The agency's key ...
banned finasteride because it was discovered that the drug could be used to mask
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
abuse. It was removed from the list effective 1 January 2009, after improvements in testing methods made the ban unnecessary. Athletes who used finasteride and were banned from international competition include
skeleton racer Skeleton is a winter sliding sport in which a person rides a small sled, known as a skeleton bobsled (or -sleigh), down a frozen track while lying face down and head-first. The sport and the sled may have been named from the bony appearance of ...
Zach Lund,
bobsledder Bobsleigh or bobsled is a team winter sport that involves making timed runs down narrow, twisting, banked, iced tracks in a gravity-powered sleigh. International bobsleigh competitions are governed by the International Bobsleigh and Skeleton Feder ...
Sebastien Gattuso,
footballer A football player or footballer is a sportsperson who plays one of the different types of football. The main types of football are association football, American football, Canadian football, Australian rules football, Gaelic football, rugby ...
Romário Romário de Souza Faria Figueiredo (born 29 January 1966), known simply as Romário (), is a Brazilian politician and a former professional footballer. A prolific striker renowned for his clinical finishing, he scored over 750 goals and was ...
, and ice hockey goaltender
José Théodore José Nicolas Théodore (born September 13, 1976) is a Canadian former professional ice hockey goaltender. He played in the National Hockey League (NHL) for the Montreal Canadiens, Colorado Avalanche, Washington Capitals, Minnesota Wild, and Flori ...
.


Miscellaneous

The U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride. The UK also has a one-month deferral period. Harold Bornstein, the former personal physician of
United States President The president of the United States (POTUS) is the head of state and head of government of the United States of America. The president directs the executive branch of the federal government and is the commander-in-chief of the United State ...
Donald Trump Donald John Trump (born June 14, 1946) is an American politician, media personality, and businessman who served as the 45th president of the United States from 2017 to 2021. Trump graduated from the Wharton School of the University of Pe ...
, stated in 2017 that Trump was taking finasteride to promote hair growth.


Research

Preliminary research suggests that
topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
finasteride may be effective in the treatment of
pattern hair loss Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...
. Topical finasteride, like the oral preparation, reduces serum DHT. DHT may be involved in the cause of
acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...
, and 5α-reductase inhibitors might be effective in the treatment of the condition. A small
retrospective study A retrospective cohort study, also called a historic cohort study, is a longitudinal cohort study used in medical and psychological research. A cohort of individuals that share a common exposure factor is compared with another group of equivalen ...
reported that finasteride was effective in the treatment of acne in women with normal
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
levels. A
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
found that finasteride was less effective than
flutamide Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair grow ...
or an
ethinylestradiol/cyproterone acetate Ethinylestradiol/cyproterone acetate (EE/CPA), also known as co-cyprindiol and sold under the brand names Diane and Diane-35 among others, is a combination of ethinylestradiol (EE), an estrogen, and cyproterone acetate (CPA), a progestin and ant ...
birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progest ...
in the treatment of acne in women with high androgen levels. Androgens and
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
s may be involved in the cause of
hidradenitis suppurativa Hidradenitis suppurativa (HS), sometimes known as acne inversa or Verneuil's disease, is a long-term dermatological condition characterized by the occurrence of inflamed and swollen lumps. These are typically painful and break open, releasing ...
(acne inversa). Two
case series A case series (also known as a clinical series) is a type of medical research study that tracks subjects with a known exposure, such as patients who have received a similar treatment, or examines their medical records for exposure and outcome. Cas ...
have reported that finasteride is effective in the treatment of hidradenitis suppurativa in girls and women. Finasteride and other antiandrogens might be useful in the treatment of
obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental and behavioral disorder in which an individual has intrusive thoughts and/or feels the need to perform certain routines repeatedly to the extent where it induces distress or impairs general ...
, but more research is needed.


References


External links

* {{Portal bar , Medicine Wikipedia medicine articles ready to translate 5α-Reductase inhibitors Androstanes Merck & Co. brands Carboxamides Hair loss medications Hair removal Delta-lactams Teratogens Tert-butyl compounds