Dehydroepiandrosterone (DHEA): Hypes and Hopes

Abstract

Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal studies, their low levels have been associated with age-related involuntary changes, including reduced lifespan. Extrapolation of animal data to humans turned DHEA into a 'superhormone' and an 'anti-aging' panacea. It has been aggressively marketed and sold in large quantities as a dietary supplement. Recent double-blind, placebo-controlled human studies provided evidence to support some of these claims. In the elderly, DHEA exerts an immunomodulatory action, increasing the number of monocytes, T cells expressing T-cell receptor gamma/delta (TCRγδ) and natural killer (NK) cells. It improves physical and psychological well-being, muscle strength and bone density, and reduces body fat and age-related skin atrophy stimulating procollagen/sebum production. In adrenal insufficiency, DHEA restores DHEA/DHEAS and androstenedione levels, reduces total cholesterol, improves well-being, sexual satisfaction and insulin sensitivity, and prevents loss of bone mineral density. Normal levels of CD4+CD25(hi) and FoxP3 (forkhead box P3) are restored. In systemic lupus erythematosus, DHEA is steroid-sparing. In an unblinded study, it induced remission in the majority of patients with inflammatory bowel disease. DHEA modulates cardiovascular signalling pathways and exerts an anti-inflammatory, vasorelaxant and anti-remodelling effect. Its low levels correlate with increased cardiovascular disease and all-cause mortality. DHEA/DHEAS appear protective in asthma and allergy. It attenuates T helper 2 allergic inflammation, and reduces eosinophilia and airway hyperreactivity. Low levels of DHEAS accompany adrenal suppression. It could be used to screen for the side effects of steroids. In women, DHEA improves sexual satisfaction, fertility and age-related vaginal atrophy. Many factors are responsible for the inconsistent/negative results of some studies. Overreliance on animal models (DHEA is essentially a human molecule), different dosing protocols with non-pharmacological doses often unachievable in humans, rapid metabolism of DHEA, co-morbidities and organ-specific differences render data interpretation difficult. Nevertheless, a growing body of evidence supports the notion that DHEA is not just an overrated dietary supplement but a useful drug for some, but not all, human diseases. Large-scale randomised controlled trials are needed to fine-tune the indications and optimal dosing protocols before DHEA enters routine clinical practice.

Analysis of the relationship between the blood concentration of several metals, macro- and micronutrients and endocrine disorders associated with male aging

“…In the elderly men (between the 70th and 80th year of age), DHEA levels do not exceed 10 %-20 % of those found in young men (Rutkowski et al 2014). The cause of this age-related decrease in DHEA-also observed for DHEAS-has not been unequivocally established.…”

Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis <i>via </i>increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis

“…The administration of E2 significantly increased the serum concentration of E2 without changing the concentration of DHEA or DHEAS. Given the wealth of evidence indicating the beneficial effect of DHEA on skeletal mass (65,(68)(69)(70)(71), BSNXD may delay bone loss in PMO by enhancing production of DHEA and DHEAS rather than E2. Furthermore, the current results also provide scientific proof for use of BSNXD by women when HRT is contraindicated.…”

“…In humans, DHEA is produced by the adrenal gland and metabolized into testosterone, estrogen, and other biologically active steroids by several tissues, including the brain, liver, kidney, and gonads (69). Accordingly, after menopause all estrogens are made locally from DHEA by the mechanisms of intracrinology (73).…”

Species specificity of an adrenal androgen-mediated kill-switch triggered by p53 inactivation

“…While systemic DHEA secreted by the adrenals plays a critical role in the development and physiological homeostasis of humans and some other primates, 38,39 rodents such as rats and mice have not evolved a zona reticularis, do not express CYP17 in adrenal or gonadal tissue, and therefore have no circulating DHEAS. Rats and mice do employ DHEA as a neurosteroid, but its use in such rodents appears to be limited to brain development and physiology.…”