There is no evidence DHEA is of benefit in treating or preventing cancer.[19] Although DHEA is postulated as an inhibitor towards glucose-6-phosphate dehydrogenase (G6PD) and suppresses leukemia cell proliferation in vitro,[20][21] DHEA may enhance G6PD mRNA expression, confounding its inhibitory effects.[22]

DHEA supplementation has not been found to be useful for memory function in normal middle aged or older adults.[25] It has been studied as a treatment for Alzheimer's disease, but there is no evidence that it is effective.[26]

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 DHEA supplementation would have any cardiovascular benefit.[27]

A meta-analysis of intervention studies shows that DHEA supplementation in elderly men can induce a small but significant positive effect on body composition that is strictly dependent on DHEA conversion into its bioactive metabolites such as androgens or estrogens.[29]

DHEA is produced naturally in the human body, but the long-term effects of its use are largely unknown.[19][30] In the short term, several studies have noted few adverse effects. In a study by Chang et al., DHEA was administered at a dose of 200 mg/day for 24 weeks with slight androgenic effects noted.[31] Another study utilized a dose up to 400 mg/day for 8 weeks with few adverse events reported.[32] A longer term study followed patients dosed with 50 mg of DHEA for 12 months with the number and severity of side effects reported to be small.[33] Another study delivered a dose of 50 mg of DHEA for 10 months with no serious adverse events reported.[34]

As a hormone precursor, there has been a smattering of reports of side effects possibly caused by the hormone metabolites of DHEA.[30][35]

DHEA is a steroid hormone. High doses may cause aggressiveness, irritability, trouble sleeping, and the growth of body or facial hair on women.[19] It also may stop menstruation and lower the levels of HDL ("good" cholesterol), which could raise the risk of heart disease.[19] 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.[19]

DHEA should not be used with tamoxifen, as it may promote tamoxifen resistance.[19] Patients on hormone replacement therapy may have more estrogen-related side effects when taking DHEA. This supplement may also interfere with other medicines, and potential interactions between it and drugs and herbs should be considered. Always tell your doctor and pharmacist about any supplements and herbs you are taking.[19]

DHEA is possibly unsafe for individuals experiencing the following conditions: pregnancy and breast-feeding, hormone sensitive conditions, liver problems, diabetes, depression or mood disorders, polycystic ovarian syndrome (PCOS), or cholesterol problems.[36] Individuals experiencing any of these conditions should consult with a doctor before taking.

Regular exercise is known to increase DHEA production in the body.[39][40]Calorie restriction has also been shown to increase DHEA in primates.[41] Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.[42]Catalpol and a combination of acetyl-carnitine and propionyl-carnitine on 1:1 ratio also improves endogenous DHEA production and release due to direct cholinergic stimulation of CRH release and an increase of IGF-1 expression respectively.

DHEA-S is the sulfate ester of DHEA. This conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily in the adrenals, the liver, and small intestine. In the blood, most DHEA is found as DHEA-S with levels that are about 300 times higher than those of free DHEA. Orally ingested DHEA is converted to its sulfate when passing through intestines and liver. Whereas DHEA levels naturally reach their peak in the early morning hours, DHEA-S levels show no diurnal variation. From a practical point of view, measurement of DHEA-S is preferable to DHEA, as levels are more stable.[citation needed]

As almost all DHEA is derived from the adrenal glands, blood measurements of DHEA-S/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have elevated levels of DHEA-S.[43]

In addition to its affinity for the androgen receptor, DHEA has also been found to bind to and activate the ERα and ERβestrogen receptors with Ki values of 1.1 μM and 0.5 μM, respectively, and EC50 values of >1 μM and 200 nM, respectively. Though it was found to be a partial agonist of the ERα with a maximal efficacy of 30–70%, the concentrations required for this degree of activation make it unlikely that the activity of DHEA at this receptor is physiologically meaningful. Remarkably however, DHEA acts as a full agonist of the ERβ with a maximal response similar to or actually slightly greater than that of estradiol, and its levels in circulation and local tissues in the human body are high enough to activate the receptor to the same degree as that seen with circulating estradiol levels at somewhat higher than their maximal, non-ovulatory concentrations; indeed, when combined with estradiol with both at levels equivalent to those of their physiological concentrations, overall activation of the ERβ was doubled. As such, it has been proposed that DHEA may be an important and potentially major endogenous estrogen in the body.[9][44]

The term "dehydroepiandrosterone" is ambiguous chemically because it does not include the specific positions within epiandrosterone at which hydrogen atoms are missing. DHEA itself is 5,6-didehydroepiandrosterone or 5-dehydroepiandrosterone. A number of naturally occurring isomers also exist and may have similar activities. Some isomers of DHEA are 1-dehydroepiandrosterone (1-androsterone) and 4-dehydroepiandrosterone. These isomers are also technically "DHEA", since they are dehydroepiandrosterones in which hydrogens are removed from the epiandrosterone skeleton.

DHEA 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. DHEA is specifically exempted from the Anabolic Steroid Control Act of 1990 and 2004.[58] It is banned from use in athletic competition.

In Australia, a prescription is required to buy DHEA, where it is also comparatively expensive compared to off-the-shelf purchases in US supplement shops. Australian customs classify DHEA as an "anabolic steroid[s] or precursor[s]" and, as such, it is only possible to carry DHEA into the country through customs if one possesses an import permit which may be obtained if one has a valid prescription for the hormone.[60]

DHEA is a prohibited substance under the World Anti-Doping Code of the World Anti-Doping Agency,[61] 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 DHEA. Mayo termed his use of DHEA as "an honest mistake," saying the DHEA was in an over-the-counter supplement and that he was unaware the supplement was banned by the NBA.[62] 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 DHEA and was suspended 10 games before the start of the 2009-10 season.[63] 2008 Olympic 400 meter champion Lashawn Merritt has also tested positive for DHEA and was banned from the sport for 21 months.[64]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 DHEA in an out-of-competition doping test.[65] In 2016 MMA fighter Fabio Maldonado revealed he was taking DHEA during his time with the UFC.[66]

In the United States, DHEA or DHEA-S have been advertised with claims that they may be beneficial for a wide variety of ailments. DHEA and DHEA-S are readily available in the United States, where they are marketed as over-the-counter dietary supplements.[67]

^Schulman, Robert A.; Dean, Carolyn (2007). Solve It With Supplements. New York City: Rodale, Inc. p. 100. ISBN978-1-57954-942-8. DHEA (Dehydroepiandrosterone) is a common hormone produced in the adrenal glands, the gonads, and the brain.

^Calfee, R.; Fadale, P. (March 2006). "Popular ergogenic drugs and supplements in young athletes". Pediatrics. 117 (3): e577–89. doi:10.1542/peds.2005-1429. PMID16510635. In 2004, a new Steroid Control Act that placed androstenedione under Schedule III of controlled substances effective January 2005 was signed. DHEA was not included in this act and remains an over-the-counter nutritional supplement.