Cortisol, and perhaps DHEA, increase after exposure to situations that a person interprets as stressful.[1][2] It has been hypothesized that DHEA may counteract some of the effects of cortisol,[3] and that having higher levels of cortisol and lower levels of DHEA after stressful situations increases the risk of negative mood states, such as depression, anxiety, or anger.[3] It does appear that DHEA supplementation decreases cortisol,[4] though its effects on subjective stress levels or mood seem less consistent. For instance, a study of DHEA supplementation in military men undergoing 12-day survival training found that supplementation of 50–75 mg per day of DHEA did not affect participants’ subjective distress ratings.[5] In another study, the researchers found that low DHEA was associated with a higher risk of negative mood mood in men during and after a social stress test. However this only reflects internal DHEA production, and does not reflect supplementation with DHEA.[1]
In a randomized, placebo-controlled trial examining the broader implications of DHEA supplementation in twenty men and women with Addison’s disease (who have damaged adrenal glands, and as a result both produce very little cortisol and typically have lower levels of DHEA and androgens), participants took either placebo or 50 mg per day of DHEA for 4 months. Even in this unique population, DHEA supplementation did not show any significant effects on mood or on ratings of wellbeing. Besides mood, participating women saw increases in testosterone, participating men saw decreases in sex hormone binding globulin (which binds to and inactivates testosterone), and participants of both sexes saw decreases in body fat mass percentage (4% on average). No side effects were observed.[6] However, the applicability of these results to people without Addison’s disease is low.