The most abundant hormone secreted by the adrenal glands, DHEA circulates in the blood as the sulfate ester, dehydroepiandrosterone-3-sulfate (DHEA-S). Both are precursors for other hormones, including estrogen and androgens ⁽¹⁾. DHEA showed chemopreventive effects ^(2) (3); blocked the development of tumors ⁽⁴⁾; and enhanced immune responses following hepatitis ⁽⁵⁾ and influenza ⁽⁶⁾ vaccinations in animal models. Although it has been postulated that DHEA may play a role in increasing immune response in acquired immune deficiency syndrome (AIDS) ⁽⁷⁾, no antiviral or immunostimulatory effects were observed in HIV-positive participants receiving DHEA ⁽⁸⁾. 

DHEA was reported effective in treating Addison’s disease ^{(13) (14) (15) (16) (17)}, major depression ⁽⁹⁾, schizophrenia-induced anxiety ⁽¹⁰⁾, systematic lupus erythematosus ⁽¹¹⁾, erectile dysfunction ⁽¹³⁾ and osteoporosis ⁽¹²⁾. Additionally, low serum DHEA-S levels were found to indicate risk of non-vertebral fractures in older men ⁽⁴⁷⁾. Topical application of DHEA in postmenopausal women increased sebum production and epidermal thickening in the hands and face ⁽¹⁸⁾, and oral use increased circulating estradiol levels ⁽⁵²⁾. However, DHEA was ineffective in treating Alzheimer’s disease ⁽¹⁹⁾, obesity in adolescents ⁽²⁰⁾, or perimenopausal symptoms ⁽²¹⁾. It also did not increase muscle mass ⁽²²⁾ or physical performance ⁽²³⁾, improve cognitive performance ⁽²⁵⁾ , or enhance insulin secretion or action ⁽²⁴⁾ in elderly individuals. Supplementation, believed to enhance physical strength, did not improve physical performance or quality of life in a study done in older men and women ⁽²⁶⁾. Conflicting data, however, suggest improvements in cognitive ⁽⁴³⁾ and physical function ⁽⁴⁴⁾ in older women. Findings also suggest DHEA may protect against hypoglycemia-associated neuroendocrine and autonomic failure ⁽⁴⁸⁾ and higher levels were associated with reduced risk of cardiovascular events ⁽⁵³⁾.

Studies on DHEA’s effects on sexual dysfunction in postmenopausal women are mixed ^(28) (29). A review determined DHEA does not improve cognitive performance in this population ⁽⁵⁴⁾ but improved dyspareunia/genitourinary syndrome in menopausal women ^(49) (55) and in female cancer survivors ^(56) (57) , and conferred positive effects on vaginal cytology in postmenopausal women with breast or gynecologic cancers ⁽⁵⁰⁾. Whether or not DHEA is effective in treating adrenal insufficiency remains unclear ^(41) (42).

Higher levels of DHEA have been associated with increased risk of ovarian ⁽⁷⁾ and breast ⁽²⁷⁾ cancers in premenopausal women. Also, elevated DHEA-S levels contributed to tamoxifen resistance and disease progression in breast cancer ⁽²⁸⁾. A case of cancer flare-up was reported in a patient with advanced prostate cancer undergoing DHEA treatment ⁽²⁹⁾. In patients receiving androgen depletion treatment for recurrent prostate cancer, increases in serum DHEA and androsterone (AST) were associated with shorter time to castration-resistant prostate cancer ⁽⁵¹⁾.