Dihydrotestosterone
Encyclopedia
Dihydrotestosterone is an androgen
or male sex hormone
. The enzyme 5α-reductase
synthesises DHT in the prostate
, testes, hair follicles, and adrenal glands. This enzyme
reduces the 4,5 double-bond of the hormone
testosterone
.
In men, approximately 5% of testosterone undergoes 5α-reduction to form the more potent androgen, dihydrotestosterone. DHT has approximately three times greater affinity for androgen receptors than testosterone and has 15-30 times greater affinity than adrenal androgens. During embryogenesis DHT has an essential role in the formation of the male external genitalia, while in the adult DHT acts as the primary androgen in the prostate and in hair follicles.
An example illustrating the significance of DHT for the development of secondary sex characteristics is congenital 5-α-reductase (5-AR) deficiency
. This gene lesion can result in pseudohermaphroditism
. This condition typically presents with underdeveloped male genitalia and prostate. These individuals are often raised as girls due to their lack of conspicuous male genitalia. In the onset of puberty, although their DHT levels remain very low, their testosterone levels elevate normally. Their musculature develops like that of other adults. After puberty, men with this condition have a large deficiency of pubic and body hair, and no incidence of male pattern baldness.
Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme aromatase
to estradiol
. Therefore, it is frequently used in research settings to distinguish between the effects of testosterone caused by binding to the androgen receptor
and those caused by testosterone's conversion to estradiol
and subsequent binding to estrogen receptor
s.
male secondary sex characteristics, including a deepened voice and facial hair. DHT plays a role in the development and exacerbation of benign prostatic hyperplasia
, as well as prostate cancer
, by enlarging the prostate gland. Prostate growth and differentiation are highly dependent on sex steroid
hormones, particularly DHT.
are commonly used for the treatment of two DHT-related conditions, male pattern baldness (MPB), and benign prostatic hyperplasia
(BPH). Dutasteride
is approved for the treatment of benign prostatic hyperplasia, and is prescribed off-label for the treatment of male pattern baldness, whereas finasteride
is approved for both conditions. Dutasteride is three times more potent than finasteride in inhibiting the type II enzyme and 100 times more potent than finasteride in inhibiting the type I form of the DHT-producing enzyme.
However, 5α-reductase inhibitors
have been shown to have persistent side effects that can continue after quitting the treatment, including diminished libido, erectile dysfunction and male breast cancer , and are suspected to have persistent cognitive side effects, including depression, brain fog and memory loss . Considering the risks for health, 5α-reductase inhibitors
should not be prescribed for aesthetic purposes only. Patients who suffer from persistent side effects can participate in dedicated forums to share experiences and help gathering data on what begins to be known as the post-finasteride syndrom .
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...
or male sex hormone
Sex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
. The enzyme 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....
synthesises DHT in the prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
, testes, hair follicles, and adrenal glands. This enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
reduces the 4,5 double-bond of the hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
testosterone
Testosterone
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...
.
Effects on sexual development
An example illustrating the significance of DHT for the development of secondary sex characteristics is congenital 5-α-reductase (5-AR) deficiency
5-alpha-reductase deficiency
5-Alpha-reductase deficiency is an autosomal recessive intersex condition caused by a mutation of the 5-alpha reductase type 2 gene.-Normal function:...
. This gene lesion can result in pseudohermaphroditism
Pseudohermaphroditism
Pseudohermaphroditism, or pseudo-hermaphroditism, is the condition in which an organism is born with secondary sex characteristics or a phenotype that is different from what would be expected on the basis of the gonadal tissue ....
. This condition typically presents with underdeveloped male genitalia and prostate. These individuals are often raised as girls due to their lack of conspicuous male genitalia. In the onset of puberty, although their DHT levels remain very low, their testosterone levels elevate normally. Their musculature develops like that of other adults. After puberty, men with this condition have a large deficiency of pubic and body hair, and no incidence of male pattern baldness.
Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme aromatase
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
to estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
. Therefore, it is frequently used in research settings to distinguish between the effects of testosterone caused by binding to the androgen receptor
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
and those caused by testosterone's conversion to estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
and subsequent binding to estrogen receptor
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
s.
Pathology
DHT is the primary contributing factor in male pattern baldness. However, female hair loss is more complex, and DHT is only one of several possible causes. Women with increased levels of DHT may develop certain androgynousAndrogyny
Androgyny is a term derived from the Greek words ανήρ, stem ανδρ- and γυνή , referring to the combination of masculine and feminine characteristics...
male secondary sex characteristics, including a deepened voice and facial hair. DHT plays a role in the development and exacerbation 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....
, as well as prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, by enlarging the prostate gland. Prostate growth and differentiation are highly dependent on sex steroid
Sex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
hormones, particularly DHT.
Treatment
5α-reductase inhibitors5-alpha-reductase inhibitor
5α-Reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...
are commonly used for the treatment of two DHT-related conditions, male pattern baldness (MPB), and 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....
(BPH). Dutasteride
Dutasteride
Dutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....
is approved for the treatment of benign prostatic hyperplasia, and is prescribed off-label for the treatment of male pattern baldness, whereas finasteride
Finasteride
Finasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
is approved for both conditions. Dutasteride is three times more potent than finasteride in inhibiting the type II enzyme and 100 times more potent than finasteride in inhibiting the type I form of the DHT-producing enzyme.
However, 5α-reductase inhibitors
5-alpha-reductase inhibitor
5α-Reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...
have been shown to have persistent side effects that can continue after quitting the treatment, including diminished libido, erectile dysfunction and male breast cancer , and are suspected to have persistent cognitive side effects, including depression, brain fog and memory loss . Considering the risks for health, 5α-reductase inhibitors
5-alpha-reductase inhibitor
5α-Reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...
should not be prescribed for aesthetic purposes only. Patients who suffer from persistent side effects can participate in dedicated forums to share experiences and help gathering data on what begins to be known as the post-finasteride syndrom .
See also
- FinasterideFinasterideFinasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
- DutasterideDutasterideDutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....
- Male pattern baldness
- Management of baldness
- 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....