Prasterone

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Prasterone
Dehydroepiandrosteron.svg
Dehidroepiandrosterona3D.png
Clinical data
Trade names Astenile, Cetovister, 17-Chetovis, Dastonil S, Deandros, Diandrone, Fidelin™, Hormobago, 17-Hormoforin, Intrarosa, 17-Ketovis, Mentalormon, Psicosterone[1]
Synonyms EL-10; GL-701; KYH-3102; Androst-5-en-3β-ol-17-one; 3β-Hydroxyandrost-5-en-17-one; 5,6-Didehydroepiandrosterone;[2] Dehydroisoepiandrosterone[1]
Routes of
administration
By mouth, vaginal (insert), intramuscular injection (as prasterone enanthate), injection (as prasterone sodium sulfate)
ATCvet code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 50%[3]
Metabolism Hepatic[3]
Metabolites Androsterone[3]
Etiocholanolone[3]
DHEA sulfate[3]
Androstenedione[3]
Androstenediol[3]
Testosterone[3]
Androstanediol[3]
Biological half-life DHEA: 25 minutes[4]
DHEA-S: 11 hours[4]
Excretion Urine
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
ECHA InfoCard 100.000.160
Chemical and physical data
Formula C19H28O2
Molar mass 288.424 g/mol
3D model (JSmol)
Melting point 148.5 °C (299.3 °F)
  (verify)

Prasterone, also known as dehydroepiandrosterone (DHEA), is a naturally occurring steroid which is used as a supplement and medication. It is an androstane derivative and a precursor of steroid hormones like testosterone and estradiol. Prasterone has weak androgenic activity, weak estrogenic activity, and neurosteroid activity, and acts as a prohormone of androgens and estrogens depending on its dosage and route of administration. As a medication, prasterone may be used to restore or increase DHEA levels in deficiency or old age, for menopausal women as a weak androgen or to treat vaginal atrophy, and, in its sulfate form, for cervical dilation during childbirth.

Medical uses[edit]

Deficiency[edit]

DHEA and DHEA sulfate are produced by the adrenal glands. In people with adrenal insufficiency such as in Addison's disease, there may be deficiency of DHEA and DHEA sulfate. In addition, levels of these steroids decrease throughout life and are 70 to 80% lower in the elderly relative to levels in young adults. As such, DHEA and DHEA sulfate levels are also lower in older people. Prasterone can be used to increase DHEA and DHEA sulfate levels in adrenal insufficiency and older age. Although there is deficiency of these steroids in such individuals, clinical benefits of supplementation, if any, are uncertain, and there is insufficient evidence at present to support the use of prasterone for such purposes.[5][6]

In clinical studies of prasterone supplementation, dosages have ranged from 20 to 1,600 mg per day.[7] In people with adrenal insufficiency, oral dosages of 20 to 50 mg/day prasterone have been found to restore DHEA and DHEA-S levels to normal ranges seen in healthy young adults.[7] Conversely, oral dosages of 100 to 200 mg/day prasterone have been found to result in supraphysiological levels of DHEA and DHEA-S.[7]

Menopause[edit]

Prasterone is sometimes used as an androgen in hormone replacement therapy (HRT) for menopause.[8] In addition to prasterone itself, a long-lasting ester prodrug of prasterone, prasterone enanthate, is used in combination with estradiol valerate for the treatment of menopausal symptoms under the brand name Gynodian Depot.[9][10][11][12][13][14]

At a high dosage of 1,600 mg/day orally for 4 weeks, treatment of postmenopausal women with prasterone has been found to increase serum levels of DHEA by 15-fold, testosterone by 9-fold, DHEA-S, androstenedione (A4), and dihydrotestosterone (DHT) all by 20-fold, and estrone and estradiol both by 2-fold.[15][16]

Atrophic vaginitis[edit]

Prasterone, under the brand name Intrarosa, is approved in the United States in a vaginal insert formulation for the treatment of atrophic vaginitis (vaginal atrophy).[17][18] The mechanism of action of prasterone for this indication is unknown, though it may involve local metabolism of prasterone into androgens and estrogens.[18]

Childbirth[edit]

As prasterone sodium sulfate (brand names Astenile, Mylis, Teloin),[19][20] the sodium salt of prasterone sulfate and an ester prodrug of prasterone, prasterone is used in Japan as an injection for the treatment of insufficient cervical ripening and cervical dilation during childbirth.[1][21][22][23][24][25][26]

Side effects[edit]

Prasterone is produced naturally in the human body, but the long-term effects of its use are largely unknown.[27][28] In the short term, several studies have noted few adverse effects. In a study by Chang et al., prasterone was administered at a dose of 200 mg/day for 24 weeks with slight androgenic effects noted.[29] Another study utilized a dose up to 400 mg/day for 8 weeks with few adverse events reported.[30] A longer term study followed patients dosed with 50 mg of prasterone for 12 months with the number and severity of side effects reported to be small.[31] Another study delivered a dose of 50 mg of prasterone for 10 months with no serious adverse events reported.[32]

As a hormone precursor, there have been reports of side effects possibly caused by the hormone metabolites of prasterone.[28][33]

It is not known whether prasterone is safe for long-term use. Some researchers believe prasterone supplements might actually raise the risk of breast cancer, prostate cancer, heart disease, diabetes,[28] and stroke. prasterone may stimulate tumor growth in types of cancer that are sensitive to hormones, such as some types of breast, uterine, and prostate cancer.[28] Prasterone may increase prostate swelling in men with benign prostatic hyperplasia (BPH), an enlarged prostate gland.[27]

Prasterone is a steroid hormone. High doses may cause aggressiveness, irritability, trouble sleeping, and the growth of body or facial hair on women.[27] It also may stop menstruation and lower the levels of HDL ("good" cholesterol), which could raise the risk of heart disease.[27] Other reported side effects include acne, heart rhythm problems, liver problems, hair loss (from the scalp), and oily skin. It may also alter the body's regulation of blood sugar.[27]

Prasterone may promote tamoxifen resistance.[27] Patients on hormone replacement therapy may have more estrogen-related side effects when taking prasterone. This supplement may also interfere with other medicines, and potential interactions between it and drugs and herbs are possible.[27]

Prasterone is possibly unsafe for individuals experiencing pregnancy, breastfeeding, hormone sensitive conditions, liver problems, diabetes, depression or mood disorders, polycystic ovarian syndrome (PCOS), or cholesterol problems.[34]

Chemistry[edit]

Prasterone, also known as androst-5-en-3β-ol-17-one, is a naturally occurring androstane steroid and a 17-ketosteroid. It is closely related structurally to androstenediol (androst-5-ene-3β,17β-diol), androstenedione (androst-4-ene-3,17-dione), and testosterone (androst-4-en-17β-ol-3-one). Prasterone is the 5-dehydro analogue of epiandrosterone (5α-androstan-3β-ol-17-one) and is also known as 5-dehydroepiandrosterone or as δ5-epiandrosterone.

Derivatives[edit]

Prasterone is used medically as the C3β esters prasterone enanthate and prasterone sodium sulfate.[1] Another derivative is fluasterone (16α-fluoro-DHEA).[15]

Society and culture[edit]

Generic name[edit]

Prasterone is the generic name of DHEA in English and Italian and its INN, USAN, and DCIT,[1][35][36][37] while its generic name is prasteronum in Latin, prastérone in French and its DCF, and prasteron in German.[36]

Marketing[edit]

In the United States, prasterone or prasterone sulfate have been advertised, under the names DHEA and DHEA-S, with claims that they may be beneficial for a wide variety of ailments. Prasterone and prasterone sulfate are readily available in the United States, where they are sold as over-the-counter dietary supplements.[38]

Regulation[edit]

United States[edit]

Prasterone is legal to sell in the United States as a dietary supplement. It is currently grandfathered in as an "Old Dietary Ingredient" being on sale prior to 1994. Prasterone is specifically exempted from the Anabolic Steroid Control Act of 1990 and 2004.[39] It is banned from use in athletic competition.

Canada[edit]

In Canada, prasterone is a Controlled Drug listed under Section 23 of Schedule IV of the Controlled Drugs and Substances Act[40] and as such is available by prescription only.

Australia[edit]

In Australia, a prescription is required to buy prasterone, where it is also comparatively expensive compared to off-the-shelf purchases in US supplement shops. Australian customs classify prasterone as an "anabolic steroid[s] or precursor[s]" and, as such, it is only possible to carry prasterone into the country through customs if one possesses an import permit which may be obtained if one has a valid prescription for the hormone.[41]

United Kingdom[edit]

Prasterone is listed as an anabolic steroid and is thus a class C controlled drug.

Sports and athletics[edit]

Prasterone is a prohibited substance under the World Anti-Doping Code of the World Anti-Doping Agency,[42] which manages drug testing for Olympics and other sports. In January 2011, NBA player O. J. Mayo was given a 10-game suspension after testing positive for prasterone. Mayo termed his use of prasterone as "an honest mistake," saying the prasterone was in an over-the-counter supplement and that he was unaware the supplement was banned by the NBA.[43] Mayo is the seventh player to test positive for performance-enhancing drugs since the league began testing in 1999. Rashard Lewis, then with the Orlando Magic, tested positive for prasterone and was suspended 10 games before the start of the 2009-10 season.[44] 2008 Olympic 400 meter champion Lashawn Merritt has also tested positive for prasterone and was banned from the sport for 21 months.[45] Yulia Efimova, who holds the world record pace for both the 50-meter and 200-meter breaststroke, and won the bronze medal in the 200-meter breaststroke in the 2012 London Olympic Games, tested positive for prasterone in an out-of-competition doping test.[46] In 2016 MMA fighter Fabio Maldonado revealed he was taking prasterone during his time with the UFC.[47]

Research[edit]

Anabolic uses[edit]

Body composition[edit]

A meta-analysis of intervention studies shows that prasterone supplementation in elderly men can induce a small but significant positive effect on body composition that is strictly dependent on prasterone conversion into its bioactive metabolites such as androgens or estrogens.[48]

Cancer[edit]

There is no evidence prasterone is of benefit in treating or preventing cancer.[27] Although prasterone is postulated as an inhibitor towards glucose-6-phosphate dehydrogenase (G6PD) and suppresses leukemia cell proliferation in vitro,[49][50] Prasterone may enhance G6PD mRNA expression, confounding its inhibitory effects.[51]

Cardiovascular disease[edit]

A review in 2003 found the then-extant evidence sufficient to suggest that low serum levels of DHEA-S may be associated with coronary heart disease in men, but insufficient to determine whether prasterone supplementation would have any cardiovascular benefit.[52]

Drug addiction[edit]

A double-blind, placebo-controlled study in adult polydrug users in a detoxification program showed the efficacy of prasterone treatment combined with psychosocial enrichment and after-care. Prasterone administration positively affected decision-making, mood and well-being as early as one month into treatment, and had a long-lasting preventive effect on relapse to drug use. In a 16-month follow-up, relapse rates of prasterone-treated subjects were only 11.5%. No adverse symptoms were found. These findings demonstrate the long-term effect of prasterone on drug relapse.[53]

Lupus[edit]

There is some evidence of short-term benefit in those with systemic lupus erythematosus but little evidence of long-term benefit or safety.[54]

Memory[edit]

Prasterone supplementation has not been found to be useful for memory function in normal middle aged or older adults.[55] It has been studied as a treatment for Alzheimer's disease, but there is no evidence that it is effective.[56]

Mood[edit]

A few small, short term clinical studies have found that prasterone improves mood but its long-term efficacy and safety, and how it compares to antidepressants, was unknown as of 2015.[57][58]

Strength[edit]

Evidence is inconclusive in regards to the effect of prasterone on strength in the elderly.[59]

In middle-aged men, no significant effect of prasterone supplementation on lean body mass, strength, or testosterone levels was found in a randomized placebo-controlled trial.[60]

References[edit]

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External links[edit]