Prasterone, also known as dehydroepiandrosterone ( DHEA) and sold under the brand name Intrarosa among others, is a medication as well as over-the-counter dietary supplement which is used to correct DHEA deficiency due to adrenal insufficiency or aging, as a component of menopausal hormone therapy, to treat dyspareunia due to vaginal atrophy, and to prepare the cervix for childbirth, among other uses.
of prasterone in women include of virilization like oily skin, acne, hirsutism, voice deepening, and increased libido, , insomnia, and others.
DHEA, the active ingredient of prasterone, was discovered in 1934.
Medical uses
Deficiency
DHEA and DHEA sulfate (DHEA-S) are produced by the
. In people with adrenal insufficiency such as in Addison's disease, there may be deficiency of DHEA and DHEA-S. In addition, levels of these steroids decrease throughout life and are 70 to 80% lower in the elderly relative to levels in young adults. Prasterone can be used to increase DHEA and DHEA-S 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.
Menopause
Prasterone is sometimes used as an androgen in menopausal hormone therapy.
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.
The current evidence of any benefit of DHEA supplementation to menopausal and postmenopausal women is inconclusive.
Whereas prasterone (DHEA) supplementation in postmenopausal women can lead to an increase in E1, E2, testosterone, DHEA, and DHEAS serum levels, and a reduction in SHBG; still, the current evidence regarding the benefits of DHEA supplementation in postmenopausal women is inconclusive—while some studies suggest potential benefits, such as improved well-being, sexual function, and possibly decreased menopausal symptoms, these findings are not universally agreed upon.
Moreover, the long-term safety data for DHEA supplementation is lacking, which is a significant concern. This is particularly relevant given that DHEA supplementation can lead to increased estrogenic availability, which could potentially have implications for conditions sensitive to hormonal levels.
Vaginal atrophy
Prasterone, under the brand name Intrarosa, is approved in the
United States in a vaginal
suppository formulation for the treatment of atrophic vaginitis.
The mechanism of action of prasterone for this indication is unknown, though it may involve local
metabolism of prasterone into androgens and estrogens.
Sexual desire
Prasterone has been used orally at a dosage of 10 mg/day to increase
sexual desire in women.
Childbirth
As the
sodium salt of prasterone sulfate (brand names Astenile, Mylis, Teloin),
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.
Available forms
Prasterone was previously marketed as a pharmaceutical medication under the brand name Diandrone in the form of a 10 mg oral tablet in the
United Kingdom.
Side effects
Prasterone is produced naturally in the human body, but the long-term effects of its use are largely unknown.
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.
Another study utilized a dose up to 400 mg/day for 8 weeks with few adverse events reported.
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.
Another study delivered a dose of 50 mg of prasterone for 10 months with no serious adverse events reported.
As a hormone precursor, there have been reports of side effects possibly caused by the hormone metabolites of prasterone.
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,
Prasterone is a steroid hormone. High doses may cause aggressiveness, irritability, trouble sleeping, and the growth of body or facial hair on women.
Prasterone may promote tamoxifen resistance in breast cancer.
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.
Prasterone has been reported to possess few or no side effects even at very high dosages (e.g., 50 times the recommended over-the-counter supplement dosage).
Pharmacokinetics
Oral uptake of prasterone is excellent. Its volume of distribution is 17.0-38.5L (whereas it is 8.5-9.3L for its active metabolite DHEA-S). Prasterone (DHEA) has a biological half-life of 15-38 min (whereas it is 7-22h for DHEA-S). 51-73% of DHEA-S and its metabolites are excreted via the renal route.
levels following a single oral dose of 300 mg
crystalline (non-micronized) or
micronization prasterone (DHEA) in
premenopausal women.
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Prasterone is metabolism into and estrogens in the body,
Metabolism
Prasterone is also reversibly transformed into its active metabolite
prasterone sulfate (DHEA-S) by steroid sulfotransferase (specifically SULT1E1 and SULT2A1), which in turn can be converted back into prasterone by steroid sulfatase.
Interconversion takes place in both adrenal and peripheral tissues.
It is transformed into androstenedione by 3β-hydroxysteroid dehydrogenase (3β-HSD), and into androstenediol by 17β-hydroxysteroid dehydrogenase (17β-HSD).
In addition, androstenedione and testosterone can be converted into estrone and estradiol by aromatase, respectively.
Dose-response of hormone levels
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, and DHT all by 20-fold, and estrone and estradiol both by 2-fold.
Although prasterone can reliably increase testosterone levels in women, this isn't similarly the case in men.
Dosing
In clinical studies of prasterone supplementation, dosages have ranged from 20 to 1,600 mg per day.
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 physiological levels seen in young healthy adults.
Micronization of prasterone has been found to significantly increase levels of DHEA-S achieved with oral administration, but to produce no significant change in levels of DHEA or testosterone levels achieved.
Chemistry
Prasterone, also known as androst-5-en-3β-ol-17-one, is a
natural product 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 δ
5 (5(6)-
dehydrogenation) analogue of
epiandrosterone (5α-androstan-3β-ol-17-one), and is also known as 5-dehydroepiandrosterone (5-DHEA) or δ
5-epiandrosterone. A positional isomer of prasterone which may have similar biological activity is 4-dehydroepiandrosterone (4-DHEA).
Derivatives
Prasterone is used medically as the C3β
prasterone enanthate and prasterone sulfate.
The C19
nor- analogue of prasterone is 19-nordehydroepiandrosterone (19-nor-DHEA), which is a prohormone of
nandrolone (19-nortestosterone).
The 5α-reduced and δ
1 (1(2)-
dehydrogenation) analogue of prasterone is 1-dehydroepiandrosterone (1-DHEA or 1-androsterone), which is a prohormone of 1-testosterone (δ
1-DHT or dihydroboldenone).
(3β-dehydroxy-16α-fluoro-DHEA) is a derivative of prasterone with minimal or no hormonal activity but other biological activities preserved.
History
DHEA was discovered, via from male
urine, by
Adolf Butenandt and
Hans Dannenbaum in 1934, and the compound was isolated from human
blood plasma by Migeon and Plager in 1954.
DHEA sulfate, the 3β-
sulfate ester of DHEA, was isolated from urine in 1944, and was found by Baulieu to be the most abundant
steroid hormone in human plasma in 1954.
From its discovery in 1934 until 1959, DHEA was referred to by a number of different names in the literature, including
dehydroandrosterone,
transdehydroandrosterone,
dehydroisoandrosterone, and
androstenolone.
The name
dehydroepiandrosterone, also known as
DHEA, was first proposed by Fieser in 1949, and subsequently became the most commonly used name of the hormone.
For decades after its discovery, DHEA was considered to be an inactive compound that served mainly as an intermediate in the
biosynthesis of androgens and estrogens from
cholesterol.
In 1965, an association between DHEA sulfate levels and aging was reported by De Nee and Vermeulen.
Following this, DHEA became of interest to the scientific community, and numerous studies assessing the relationship between DHEA and DHEA sulfate levels and aging were conducted.
Prasterone, the proposed and recommended of DHEA and the term used when referring to the compound as a medication, were published in 1970 and 1978, respectively.
In 2001, Genelabs submitted a New Drug Application of prasterone for the treatment of systemic lupus erythematosus (SLE) to the FDA.
Society and culture
Generic names
Prasterone is the
generic term of DHEA in
English language and
Italian language and its International Nonproprietary Name, United States Adopted Name and Italian Common Name,
while its generic name is
prasteronum in
Latin language,
prastérone in
French language and its French popular name, and
prasteron in German.
Marketing
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.
In 1996, reporter Harry Wessel of the Orlando (Florida) Sentinel wrote about DHEA that "Thousands of people have gotten caught up in the hoopla and are buying the stuff in health food stores, pharmacies and mail-order catalogs" but that "such enthusiasm is viewed as premature by many in the medical field." He noted that "National publications such as Time, Newsweek and USA Today have run articles recently about the hormone, while several major publishers have come out with books touting it."
The product was being "widely marketed to and used by bodybuilders," Dr. Paul Donahue wrote in 2012 for King Features syndicate.
Regulation
By country
Australia
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 steroids or precursors" 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.
Canada
In Canada, prasterone is a Controlled Drug listed under Section 23 of Schedule IV of the
Controlled Drugs and Substances Act and as such is available by prescription only.
United Kingdom
Prasterone is listed as an
anabolic steroid and is thus a class C controlled drug.
United States
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.
Sports and athletics
Prasterone is banned from use in athletic competition.
It is a prohibited substance under the World Anti-Doping Code of the World Anti-Doping Agency,
which manages drug testing for Olympics and other sports.
-
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.
-
Rashard Lewis, then with the Orlando Magic, tested positive for prasterone and was suspended 10 games before the start of the 2009–10 season.
-
In 2016 MMA fighter Fabio Maldonado revealed he was taking prasterone during his time with the UFC.
-
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.
-
Olympic 400-meter champion Lashawn Merritt tested positive for prasterone in 2010 and was banned from the sport for 21 months.
-
Tennis player Venus Williams had permission from the International Tennis Federation to use DHEA along with hydrocortisone as a treatment for "adrenal insufficiency," but it was revoked in 2016 by the World Anti-Doping Agency, which believed DHEA use would enhance Williams' athletic performance.
Research
Anabolic uses
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.
Evidence is inconclusive in regards to the effect of prasterone on strength in the elderly.
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.
Cancer
There is no evidence prasterone is of benefit in treating or preventing
cancer.
Cardiovascular disease
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.
Prasterone may enhance G6PD mRNA expression, confounding its inhibitory effects.
Lupus
There is some evidence of short-term benefit in those with systemic lupus erythematosus but little evidence of long-term benefit or safety.
Prasterone was under development for the treatment of systemic lupus erythematosus in the
United States and
Europe in the 1990s and 2000s and reached phase III
and preregistration for this indication, respectively, but ultimately development was not continued past 2010.
Memory
Prasterone supplementation has not been found to be useful for memory function in normal middle aged or older adults.
It has been studied as a treatment for Alzheimer's disease, but there is no evidence that it is effective or ineffective. More research is needed to determine its benefits.
Mood
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.
See also
-
List of investigational sexual dysfunction drugs
Further reading
