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 old age, as a component of menopausal hormone therapy, to treat painful sexual intercourse due to vaginal atrophy, and to prepare the cervix for childbirth, among other uses.

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.

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.

[2][33][34][35][36][37][38] 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.

[42] 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.

High doses may cause aggressiveness, irritability, trouble sleeping, and the growth of body or facial hair on women.

[39] It also may stop menstruation and lower the levels of HDL cholesterol, which could raise the risk of heart disease.

[39] It may also increase the risk of uterine and prostate cancers due to metabolism into estrogens and androgens, respectively.

[47]Prasterone is metabolized into androgens and estrogens in the body,[12][52] including androstenedione, testosterone, estrone, estradiol, and estriol.

[47] The transformation of prasterone into androgens and estrogens is tissue-specific, for instance occurring in the liver, fat, vagina, prostate gland, skin, and hair follicles (as well as other tissues).

[12][52] 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.

[9][11] 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.

[11] For decades after its discovery, DHEA was considered to be an inactive compound that served mainly as an intermediate in the production of androgens and estrogens from cholesterol.

[9][11] Prasterone, the proposed INNTooltip International Nonproprietary Name and recommended INN of DHEA and the term used when referring to the compound as a medication, were published in 1970 and 1978, respectively.

[64][65][66][67] In the early 1980s, prasterone became available and was widely sold over-the-counter as a non-prescription supplement in the United States, primarily as a weight loss aid.

[9][69] In 2001, Genelabs submitted a New Drug Application of prasterone for the treatment of systemic lupus erythematosus (SLE) to the FDA.

[9] In 2016, the FDA approved prasterone in an intravaginal gel formulation for the treatment of painful sexual intercourse due to vulvovaginal atrophy in the United States under the brand name Intrarosa.

[77] 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.

[91] 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.

[39] 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.

[9][71][70] Prasterone supplementation has not been found to be useful for memory function in normal middle aged or older adults.

[97] 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.