5-alpha-reductase inhibitor
Encyclopedia
5α-Reductase inhibitors are a group of drugs
with antiandrogen
ic activity, used in the treatment of benign prostatic hyperplasia
and androgenic (or androgenetic) alopecia
. These drugs decrease the levels of available 5α-reductase
prior to testosterone's binding with the enzyme, thus reducing levels of dihydrotestosterone
that derives from such a bond.
. To be specific, these indications may include:
s (ADRs) experienced with 5α-reductase inhibitors are dose-dependent. Common ADRs include impotence, decreased libido
, decreased ejaculate volume, depression, and anxiety
. Rare ADRs include breast tenderness and enlargement (gynecomastia
), and allergic
reaction.
The FDA has notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer).
to the active form dihydrotestosterone
(DHT) by reducing the Δ4,5 double-bond. In benign prostatic hyperplasia
, dihydrotestosterone acts as a potent cellular androgen
and promotes prostate
growth; therefore, inhibiting the enzyme reduces the excessive prostate growth. In alopecia, male-pattern baldness is one of the effects of androgenic receptor activation. Thus, reducing the levels of dihydrotestosterone reduces alopecia.
Zinc
, azelaic acid
, β-sitosterol, certain unsaturated aliphatic fatty acid
s such as gamma-linolenic acid
, alpha-linolenic acid
, linoleic acid
, and oleic acid
, and a variety of polyphenol
s have been found to inhibit 5α-reductase activity to varying degrees.
Certain pesticides are able to disturb the sex steroid hormone system and to act as antiandrogens.
or organoderol B may be the active compounds.
Medium chain fatty acids such as those found in coconut
and the kernel of many palm fruits have also been found to inhibit 5α-reductase.
Other herbs include:
None of these plants have been tested in human clinical trial
s and their potential for the treatment of BPH and related conditions is unknown.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
with antiandrogen
Antiandrogen
Antiandrogens, or androgen antagonists, first discovered in the 1960s, prevent androgens from expressing their biological effects on responsive tissues. Antiandrogens alter the androgen pathway by blocking the appropriate receptors, competing for binding sites on the cell's surface, or affecting...
ic activity, used in the treatment of benign prostatic hyperplasia
Benign prostatic hyperplasia
Benign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
and androgenic (or androgenetic) alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
. These drugs decrease the levels of available 5α-reductase
5-alpha reductase
5α-reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer....
prior to testosterone's binding with the enzyme, thus reducing levels of dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
that derives from such a bond.
Indications
5α-Reductase inhibitors are clinically used in the treatment of conditions that are exacerbated by dihydrotestosteroneDihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
. To be specific, these indications may include:
- mild-to-moderate benign prostatic hyperplasiaBenign prostatic hyperplasiaBenign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
and lower urinary tract symptomsLower urinary tract symptomsLower urinary tract symptoms are a common problem affecting approximately 40% of older men. LUTS is a recent term for what used to be known as prostatism.-Voiding or obstructive symptoms:*Poor stream*Hesitancy*Terminal dribbling... - androgenic (or androgenetic) alopeciaAlopeciaAlopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
. - prostate cancer (controversial)
Adverse drug reactions
In general, adverse drug reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s (ADRs) experienced with 5α-reductase inhibitors are dose-dependent. Common ADRs include impotence, decreased libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
, decreased ejaculate volume, depression, and anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
. Rare ADRs include breast tenderness and enlargement (gynecomastia
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
), and allergic
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
reaction.
The FDA has notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer).
Pharmacology
The enzyme 5α-reductase is involved in the conversion of testosteroneTestosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
to the active form dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
(DHT) by reducing the Δ4,5 double-bond. In benign prostatic hyperplasia
Benign prostatic hyperplasia
Benign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
, dihydrotestosterone acts as a potent cellular androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
and promotes prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
growth; therefore, inhibiting the enzyme reduces the excessive prostate growth. In alopecia, male-pattern baldness is one of the effects of androgenic receptor activation. Thus, reducing the levels of dihydrotestosterone reduces alopecia.
Examples
- Pharmaceuticals
- AlfatradiolAlfatradiolAlfatradiol is a 5α-reductase inhibitor used topically for the treatment of androgenic alopecia in men and women.-Uses:...
(Ell-Cranell Alpha, Pantostin) - DutasterideDutasterideDutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....
(Avodart) - FinasterideFinasterideFinasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
(Proscar, Propecia)
- Alfatradiol
- Research chemicals
- BexlosterideBexlosterideBexlosteride is a potent and noncompetitive inhibitor of the enzyme 5α-reductase related to finasteride and dutasteride. It is selective for the type I isoform of the enzyme. It was never marketed.- References :...
(LY-191,704) - EpristerideEpristerideEpristeride is a selective, transition state, non-competitive inhibitor of the type II isoform of the enzyme 5α-reductase, similarly to finasteride and turosteride...
(SKF-105,657, ONO-9302) - IzonsterideIzonsterideIzonsteride is a selective inhibitor of the 5α-redcutase, with dual effects on both the type I and type II isoforms of the enzyme. It was under development by Eli Lilly and Company and Fujisawa for the treatment of benign prostatic hyperplasia but was never marketed...
(LY-320,236) - LapisterideLapisterideLapisteride is a dual inhibitor of both isoforms of the enzyme 5α-reductase. It was under investigation for the treatment of benign prostatic hyperplasia and androgenic alopecia, but was never marketed.- References :...
(CS-891) - TurosterideTurosterideTurosteride is a selective inhibitor of the enzyme 5α-redcutase which was under investigation by GlaxoSmithKline for the treatment of benign prostatic hyperplasia , but was never marketed. Similarly to finasteride, turosteride is selective for the type II isoform of 5α-redcutase, with about...
(FCE-26,073)
- Bexlosteride
Zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, azelaic acid
Azelaic acid
Azelaic acid is an organic compound with the formula 72. This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a component of a number of hair and skin conditioners.-Production:...
, β-sitosterol, certain unsaturated aliphatic fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s such as gamma-linolenic acid
Gamma-Linolenic acid
γ-Linolenic acid is a fatty acid found primarily in vegetable oils...
, alpha-linolenic acid
Alpha-linolenic acid
α-Linolenic acid is an organic compound found in many common vegetable oils. In terms of its structure, it is named all-cis-9,12,15-octadecatrienoic acid. In physiological literature, it is given the name 18:3 ....
, linoleic acid
Linoleic acid
Linoleic acid is an unsaturated n-6 fatty acid. It is a colorless liquid at room temperature. In physiological literature, it has a lipid number of 18:2...
, and oleic acid
Oleic acid
Oleic acid is a monounsaturated omega-9 fatty acid found in various animal and vegetable fats. It has the formula CH37CH=CH7COOH. It is an odorless, colourless oil, although commercial samples may be yellowish. The trans isomer of oleic acid is called elaidic acid...
, and a variety of polyphenol
Polyphenol
Polyphenols are a structural class of natural, synthetic, and semisynthetic organic chemicals characterized by the presence of large multiples of phenol structural units...
s have been found to inhibit 5α-reductase activity to varying degrees.
Certain pesticides are able to disturb the sex steroid hormone system and to act as antiandrogens.
Herbs
Many chemical compounds in nature are able to inhibit 5α-reductase, such as those found in the Reishi mushroom Ganoderma lucidum. Ganoderic acidGanoderic acid
Ganoderic acids are a class of closely related triterpenoids found in Ganoderma mushrooms. For thousands of years, the fruiting bodies of Ganoderma fungi have been used in traditional medicines in East Asia. Consequently, there have been efforts to identify the chemical constituents that may be...
or organoderol B may be the active compounds.
Medium chain fatty acids such as those found in coconut
Coconut
The coconut palm, Cocos nucifera, is a member of the family Arecaceae . It is the only accepted species in the genus Cocos. The term coconut can refer to the entire coconut palm, the seed, or the fruit, which is not a botanical nut. The spelling cocoanut is an old-fashioned form of the word...
and the kernel of many palm fruits have also been found to inhibit 5α-reductase.
Other herbs include:
- Angelica koreana
- Impatiens balsaminaImpatiens balsaminaImpatiens balsamina is a species of Impatiens native to southern Asia in India and Myanmar.It is called kamantigue in the Philippines. This species of Kalamantigue are used in teas...
- Brassica rapaBrassica rapaBrassica rapa L. , commonly known as turnip, turnip rape, field mustard or turnip mustard is a plant widely cultivated as a leaf vegetable , a root vegetable , and an oilseed .In the 18th century the turnip and...
(pollenPollenPollen is a fine to coarse powder containing the microgametophytes of seed plants, which produce the male gametes . Pollen grains have a hard coat that protects the sperm cells during the process of their movement from the stamens to the pistil of flowering plants or from the male cone to the...
) - Cuscuta reflexaCuscutaCuscuta is a genus of about 100-170 species of yellow, orange or red parasitic plants. Formerly treated as the only genus in the family Cuscutaceae, recent genetic research by the Angiosperm Phylogeny Group has shown that it is correctly placed in the morning glory family, Convolvulaceae...
- Euphorbia jolkinii
- Ganoderma lucidum
- Polygonum multiflorum
- Piper nigrum (leaf extract)
- Pygeum africanum
- Serenoa repens or saw palmetto (active substance possibly lauric acidLauric acidLauric acid , the saturated fatty acid with a 12-carbon atom chain, is a white, powdery solid with a faint odor of bay oil or soap.-Occurrence:...
) - Pinus sp. (resinResinResin in the most specific use of the term is a hydrocarbon secretion of many plants, particularly coniferous trees. Resins are valued for their chemical properties and associated uses, such as the production of varnishes, adhesives, and food glazing agents; as an important source of raw materials...
, active substance abietic acidAbietic acidAbietic acid , an organic compound that occurs widely in trees. It is the primary component of resin acid, is the primary irritant in pine wood and resin, isolated from rosin and is the most abundant of several closely related organic acids that constitute most of rosin, the solid portion of the...
) - Sophora flavescensSophora flavescensSophora flavescens is a species of plant in the genus Sophora. Ku shen or kushenin is a typical traditional Chinese medicine that is found in this plant...
- Torilis japonicaTorilis japonicaTorilis japonica, the Japanese hedge parsley, is a plant species in the genus Torilis....
- Thuja occidentalisThuja occidentalisThuja occidentalis is an evergreen coniferous tree, in the cypress family Cupressaceae, which is widely cultivated for use as an ornamental plant known as American Arbor Vitae. The endemic occurrence of this species is a northeastern distribution in North America...
- Spore of Lygodium japonicumLygodium japonicumLygodium japonicum is a species of fern that is known by the common name Japanese climbing fern. It is native to eastern Asia, including Japan, Korea, southeastern Asia, and India, and eastern Australia...
None of these plants have been tested in human clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s and their potential for the treatment of BPH and related conditions is unknown.