The sulfate derivative of DHEA has been shown to act as a noncompetitive antagonist of gamma-aminobutyric acid (GABA) receptors, as well as a positive allosteric modulator of N-methyl-D-aspartate receptors. In humans, neuroprotective, antioxidant, antihypertensive, and anti-inflammatory effects have also been reported. Serum DHEA levels peak in 60 to 480 minutes after administration.

Adequately powered, long-term clinical trials are lacking to support therapeutic use of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) supplementation (hereafter jointly referred to as DHEA/S). Reviews of clinical trials found no convincing evidence to support a place in therapy for DHEA in improving cognitive function or physical strength in elderly patients, or in treating postmenopausal symptoms in women, hyperlipidemia or insulin resistance, schizophrenia, or cancer. Some evidence exists to support the use of DHEA/S supplementation in women with diminished ovarian reserves, in subpopulations of elderly women with osteoporosis, and in mild systemic lupus erythematosus. DHEA is recommended as third-line monotherapy or adjunctive therapy for treatment of major depressive disorder (MDD) by Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines, and limited data suggest a potential role for DHEA as an anxiolytic.

Adrenal insufficiency: 50 mg/day for 3 months is considered a replacement dose, while 200 mg/day achieves supraphysiological circulating levels and is considered a pharmacological dose.

Anorexia nervosa: 100 mg/day for 6 months was used in a pilot study.

Diminished ovarian reserve: 50 to 75 mg/day (in divided doses) has been used in clinical studies of assisted reproduction.

Exercise training–induced muscle damage: 100 mg/day of Dehydroepiandrosterone supplementation was administered over 5 days in a study in young men undergoing exercise training.

Major depressive disorder: Doses ranging from 30 to 450 mg/day for 6 to 8 weeks have been used in clinical studies.

Metabolic syndrome: 100 mg/day for 3 months has been used in a study evaluating effects against metabolic syndrome in pre-and postmenopausal women.

Postmenopausal women: 25 mg/day has been suggested because this dose minimizes androgenic adverse effects; however, only studies in which at least 50 mg/day was used demonstrated positive outcomes as hormonal replacement therapy.

Use of Dehydroepiandrosterone is not recommended in breast or prostate cancer.

Studies in adrenal insufficiency suggest DHEA is generally well tolerated. However, data from long-term studies are lacking. Observed adverse effects include mania and hypomania, acne, hirsutism, gynecomastia, testicular changes, increased blood pressure, and decreased high-density lipoprotein (HDL) levels.

Use caution in individuals with psychiatric disorders; agitation, confusion, anxiety, paranoia, and suicidal thoughts have been reported. Use of hormones like DHEA may cause erythrocytosis. Use caution in individuals with diabetes, as DHEA may increase insulin resistance or sensitivity. Use caution in individuals with liver dysfunction, as DHEA may exacerbate this condition. Use caution in individuals with polycystic ovarian syndrome, as DHEA may worsen this condition.

Pregnancy & Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Dehydroepiandrosterone supplementation has been evaluated for use in improving oocyte production in infertility.