Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone.

The 5α-reductase enzyme catalyzes the formation of DHT from testosterone in certain tissues including the prostate gland, seminal vesicles, epididymides, skin, hair follicles, liver, and brain.

The 5α-reductase enzyme mediates reduction of the C4-5 double bond of testosterone.

DHT is considerably more potent as an agonist of the androgen receptor (AR) than testosterone.

Routes of administration include: Transdermal (gel), in the cheek, under the tongue, intramuscular injection.

Bioavailability for oral administration is very low due to extensive first pass metabolism.

DHT has been used as a medication in the treatment of low testosterone levels in men.

DHT has biological importance for sexual differentiation of the male genitalia during embryogenesis, maturation of the penis and scrotum at puberty, growth of facial, body, and pubic hair, and development and maintenance of the prostate gland and seminal vesicles.

Physiologically DHT signals are intracrine and paracrine rather than a circulating hormone phenomenon.

Circulating levels of DHT are 1/10th and 1/20th those of testosterone in terms of total and free concentrations, respectively.

DHT levels locally may be up to 10 times those of testosterone in tissues with high 5α-reductase expression such as the prostate gland.

Serum DHT levels are about 10% of those of testosterone, but levels in the prostate gland are 5- to 10-fold higher than those of testosterone due to a more than 90% conversion of testosterone into DHT by locally expressed 5α-reductase.

DHT as an AR agonist is much more potent than is testosterone, and is considered to be the major androgen of the prostate gland.

DHT inactivated by 3α-hydroxysteroid dehydrogenase (3α-HSD) into the very weak androgen 3α-androstanediol in various tissues such as muscle, adipose, and liver among others.

DHT has been reported to be a very poor anabolic agent when administered exogenously.

DHT has role in a number of androgen-dependent conditions including hair conditions like hirsutism, and pattern hair loss and prostate diseases such as benign prostatic hyperplasia (BPH) and prostate cancer.

5α-Reductase inhibitors, which prevent DHT synthesis, are effective in the prevention and treatment of these conditions.

Metabolites of DHT can act as neurosteroids

Metabolites of DHT have their own AR-independent biological activity.

3α-Androstanediol is a potent positive modulator of the GABAA receptor, and selective agonist of the estrogen receptor (ER) subtype ERβ.

Metabolites may play important roles in the central effects of DHT and by extension testosterone,including: antidepressant, anxiolytic, hedonic, anti-stress, and pro-cognitive effects.

Neither BPH nor prostate cancer have been reported in 5α-reductase type II deficiency

Genetic males with the condition generally show oligozoospermia due to undescended testes.

Spermatogenesis is reported to be normal in those with testes that have descended.

Genetic females with 5α-reductase type II deficiency are phenotypically normal, but show reduced body hair growth, including an absence of hair on the arms and legs, slightly decreased axillary hair, and moderately decreased pubic hair.

Sebum secretion appears to be entirely under the control of 5α-reductase type I.

5α-Reductase inhibitors like finasteride and dutasteride were developed and are used primarily for the treatment of BPH-they inhibit 5α-reductase type II and are able to decrease circulating DHT levels by 65 to 98% depending on the 5α-reductase inhibitor.

5α-Reductase inhibitors significantly reduce the size of the prostate gland and to alleviate symptoms of the condition.

Long-term treatment with 5α-reductase inhibitors significantly reduce the overall risk of prostate cancer, although a simultaneous small increase in the risk of certain high-grade tumors has been observed.

5α-reductase inhibitors can be for the treatment of pattern hair loss in men, preventing further hair loss in most men with the condition and to produce some recovery of hair in about two-thirds of men.

5α-Reductase inhibitors are less effective for pattern hair loss in women.

5α-Reductase inhibitors are also useful in the treatment of hirsutism and can greatly reduce facial and body hair growth in women.

5α-Reductase inhibitors are well-tolerated with low incidence of adverse effects.

Sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate volume, may occur in 3.4-15.8% of men treated with 5α-Reductase inhibitors.

A very small risk of gynecomastia has been associated with 5α-reductase inhibitors.

5α-reductase inhibitors may cause birth defects such as ambiguous genitalia in the male fetuses of pregnant women, and are not used in women during pregnancy.

DHT is a potent agonist of the androgen receptor.

It is in fact the most potent known endogenous ligand of the receptor (AR).

It has an affinity for the human AR, which is about 2- to 3-fold higher than that of testosterone and 15–30 times higher than that of adrenal androgens.

The dissociation rate of DHT from the AR is 5-fold slower than that of testosterone.

DHT has been found to be 2.5- to 10-fold more potent than testosterone in bioassays,

The elimination half-life of DHT in the body is 53 minutes.

The elimination half-life of testosterone is 34 minutes.

Transdermal DHT and testosterone terminal half-lives of 2.83 hours and 1.29 hours, respectively.

Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme aromatase into an estrogen like estradiol.

DHT is transformed into metabolites with significant ER affinity and activity, which are 3α-androstanediol and 3β-androstanediol, which are predominant agonists of the ERβ.

Around 5 to 7% of testosterone undergoes 5α-reduction into DHT.

Approximately 200 to 300 μg of DHT is synthesized in the body per day.

Most DHT is produced in peripheral tissues like the skin and liver.

Most circulating DHT originates specifically from the liver.

The testes and prostate gland contribute relatively little to concentrations of DHT in circulation.

It is unique in that it is the only major sex hormone that functions principally as an intracrine and paracrine hormone rather than as an endocrine hormone.

There are two major isoforms of 5α-reductase, SRD5A1 (type I) and SRD5A2 (type II)

Type II is the most biologically important isoenzyme, and is most highly expressed in the genitals, prostate gland, epididymides, seminal vesicles, genital skin, facial and chest hair follicles, and liver, while lower expression is observed in certain brain areas, non-genital skin/hair follicles, testes, and kidneys.

A third 5α-reductase: SRD5A3 also exists.

Type I, SRD5A1, is most highly expressed in non-genital skin/hair follicles, the liver, and certain brain areas, while lower levels are present in the prostate, epididymides, seminal vesicles, genital skin, testes, adrenal glands, and kidneys.

In the skin, 5α-reductase is expressed in sebaceous glands, sweat glands, epidermal cells, and hair follicles.

Both 5α-reductase isoenzymes are expressed in scalp hair follicles, with SRD5A2 predominant in these cells.

DHT is plasma protein bound more than 99%.

In men, approximately 0.88% of DHT is unbound, and is bound 49.7% to sex hormone-binding globulin (SHBG), 39.2% to albumin, and 0.22% to corticosteroid-binding globulin (CBG).

It has higher affinity for SHBG than does testosterone, estradiol, or any other steroid hormone.

Plasma protein binding of testosterone: Free 23%, SHBG 2.23%, CBG 35.6% Albumin 49.9%

Plasma protein binding of DHT: Free 1.7%, SHBG 0.88%, CBG 49.7%, Albumin 39.2%

It is inactivated in the liver and extrahepatic tissues like the skin into 3α-androstanediol and 3β-androstanediol by the enzymes 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase, respectively.

Its metabolites are converted, into androsterone and epiandrosterone, then conjugated by glucuronidation and/or sulfation, and are released into circulation, and excreted in urine.

Available for medical use as an androgen or anabolic–androgenic steroid.

Used mainly in the treatment of male hypogonadism.

It is not available in the United States.

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