Module 6: Exploring Age-Related Body Systems Changes

6.2: Endocrine System

6.2.12: Dehydroepiandrosterone (DHEA)

Dehydroepiandrosterone, or more simply, DHEA, is another steroid produced by the adrenal glands that is getting a great deal of attention from individuals interested in aging.

DHEA is formed in the process of producing the various adrenal steroid hormones. There are really three forms: unconjugated; sulphated (DHEA-S), which is the most common form in the blood and is often the one that is measured; and lipoidal, about which much less is known. Hornsby (1997) notes that the human pattern of DHEA(S) biosynthesis is a fairly recent evolutionary development rather than something inherited from ancestors for whom it had a function and is no longer needed. This suggests that DHEA(S) has an important function in adults, especially after the start of puberty.

Levels of DHEA are noted to decrease significantly with age (de Bruin, Vieira, et al., 2002; Ferrari, Casarotti, et al., 2001; Timiras, 2003) although there may be differences between men and women (Tilvis, R.S., Kähönen, & Härkönen, 1999). The response to ACTH is also decreased (Giordano, Di Vito et al., 2001). These changes are believed to be due to a blockage in the synthetic pathway of the hormone - that is, a primary failure in hormone synthesis—possibly related to changes in the zona reticularis of the gland (Giordano, Di Vito et al., 2001), although this remains to be proven.

Of clinical importance, many biological effects have been attributed to DHEA, including improved memory, increased lean body mass, enhanced immuno-competence, and increased longevity. DHEA’s influence on longevity is thought to be through an effect on glucose 6-phosphate dehydrogenase activity and subsequently on NADPH stimulated lipogenesis. However, data are conflicting and there are concerns about its long term effects.

Studies have suggested that DHEA did not benefit persons with physiological, age-related declines, that levels are not correlated with cognition or well-being, and that treatment had no effect on bone health in men (Allolio & Arlt, 2003; Kahn & Halloran, 2002; van Niekerk, Huppert et al., 2001; Moffat, Zonderman, et al., 2000). In contrast, other studies have identified positive effects on bone as well as other parameters of well-being (Labrie, Luu-The, et al., 2001; Baulieu, Thomas, et al., 2000).

While animal studies have been done, sometimes with positive outcomes, data suggest some animals may not be appropriate models. For example, rodents do not synthesize DHEA(S) in the adrenal glands and do not maintain high plasma levels of DHEAS when given large doses of DHEA (Hornsby, 1997). Miller (1997) even noted in this regard that “those of us who work in animal models need to remain watchful for exceptions to our tacit assumption that mice are simply small nocturnal people with prominent whiskers” (p.1402).

Because of its purported effects, DHEA is now a popular nutritional supplement. However, it can have significant side effects because it is a steroid—for example, it can be converted to potent androgens and estrogens and has been linked to hirsutism, acne, and menstrual irregularities among other things (Svec, 1997). Long term effects on the occurrence of cancer are currently not know. Svec (1997), among others, cautions about over the counter use noting that while the usual dose is about 50-100mg/day the purity of the supplements is not clear and DHEA can increase hepatic size, change hepatic texture, and change hepatic chemistry.

Given the range of its effects and its potential to promote hormone sensitive cancers, it is important to ask whether an older adult is using a DHEA supplement, and to continue to evaluate subsequent studies for further information on the pros and cons of its use.