A Review of Age-Related Dehydroepiandrosterone Decline and Its Association with Well-Known Geriatric Syndromes: Is Treatment Beneficial?

Abstract

Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in humans. DHEA levels fall with age in men and women, reaching values sometimes as low as 10%-20% of those encountered in young individuals. This age-related decrease suggests an ''adrenopause'' phenomenon. Studies point toward several potential roles of DHEA, mainly through its hormonal end products, making this decline clinically relevant. Unfortunately, even if positive effects of DHEA on muscle, bone, cardiovascular disease, and sexual function seem rather robust, extremely few studies are large enough and/or long enough for conclusions regarding its effects on aging. Moreover, because it has been publically presented as a ''fountain of youth'' equivalent, overthe-counter preparations lacking pharmacokinetic and pharmacodynamic data are widely used worldwide. Conceptually, supplementing a pre-hormone is extremely interesting, because it would permit the human organism to adequately use it throughout long periods, increasing or decreasing end products according to his needs. Nevertheless, data on the safety profile of long-term DHEA supplementation are still lacking. In this article, we examine the potential relation between low DHEA levels and well-known age-related diseases, such as sarcopenia, osteoporosis, dementia, sexual disorders, and cardiovascular disease. We also review risks and benefits of existing protocols of DHEA supplementation.

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

“…Although no specific intra-nuclear receptors of DHEA have been identified to date (14), studies have found that both ERs (15) and androgen receptors (ARs) (15) are involved in mediating the Figure 1. Administration of BSNXD increased serum levels of DHEA and DHEAS but not E2.…”

Estrogen Regulation of Fetal Adrenal Cortical Zone-Specific Development in the Nonhuman Primate Impacts Adrenal Production of Androgen and Cortisol and Response to ACTH in Females in Adulthood

“…As reviewed by Samaras et al (9), numerous studies suggest several important roles for DHAS and specific high-affinity membrane receptors for DHAS have been identified and localized to several tissues (36 -39). In addition to potential direct effects, DHAS may elicit its effects via conversion to other androgenic and/or estrogenic metabolites (9).…”

“…In addition to potential direct effects, DHAS may elicit its effects via conversion to other androgenic and/or estrogenic metabolites (9). It has also been shown that DHAS can inhibit production of inflammatory cytokines and improve insulin sensitivity (9).…”

“…It is well established that after birth the fetal adrenal DZ, TZ, and FZ differentiate and remodel into glomerulosa, fasciculata, and reticular zones, respectively, which comprise the adult adrenal gland (5-7). In the adult, these respective adrenal cortical zones produce the mineralocorticoid aldosterone, the glucocorticoid cortisol and the androgen DHAS, which in addition to serving as an estrogen precursor in peripheral tissue is thought to play a role in "protecting" individuals from age-dependent changes in several physiologic parameters, eg, neurologic dysfunction (8,9).…”

DHEA prevents bone loss by suppressing the expansion of CD4⁺ T cells and TNFa production in the OVX-mouse model for postmenopausal osteoporosis

“…However, only DHEA can be converted into more potent androgens and estrogens in peripheral tissues, while DHEAS is maintained as a circulating stock (3). In premenopausal women, 50-75% of estrogens, and the majority of androgens, are produced from DHEA, while almost all androgens and estrogens are synthesized from it during postmenopause (5). Postmenopausal osteoporosis (PMO) is a well-known estrogen deficiency-induced geriatric syndrome and is also a worldwide health problem.…”