Elsevier

Mayo Clinic Proceedings

Volume 78, Issue 10, October 2003, Pages 1257-1273
Mayo Clinic Proceedings

Review
Dehydroepiandrosterone: Is There a Role for Replacement?

https://doi.org/10.4065/78.10.1257Get rights and content

Dehydroepiandrosterone (DHEA) and its sulfated ester are found in high concentrations in the plasma; however, their role in normal human physiology, other than as precursors for sex hormones, remains incompletely defined. Studies of rodent models have shown that these hormones have beneficial effects on a wide variety of conditions, such as diabetes, obesity, immune function, atherosclerosis, and many of the disorders associated with normal aging. However, rodents are not the best models to study the actions of these hormones because they have very little endogenous DHEA; thus, the doses given to these animals are usually suprapharmacological. Human studies have been performed to determine the potential beneficial effects of DHEA replacement in persons with low DHEA levels. Results have been conflicting. Human studies suggest a potential role for DHEA replacement in persons who have undergone adrenalectomy and possibly in the aging population. However, long-term studies assessing the benefits vs adverse effects must be done before DHEA replacement can be recommended.

Section snippets

BIOCHEMISTRY AND PHYSIOLOGY OF DHEA

DHEA and DHEAS are 2 of the major C19 steroids secreted by the zona reticularis region of the adrenal glands. As with all C19 steroids, these hormones are products of cholesterol metabolism and are derived from the action of CYP11A (cytochrome P-450scc) on the inner membrane of the highly active mitochondria found in the adrenal cortex.2 In humans, DHEA and DHEAS are the most abundant circulating steroid hormones. Their role remains to be fully elucidated. DHEAS can be readily converted to

Mood and Well-being

Sex hormones are known to play an important role in mood and well-being in both sexes (Table 1). Because levels of these hormones decline with aging, there is a parallel deterioration of mental function, and DHEA replacement is thought to be of potential benefit.

As a neuroactive neurosteroid, DHEA has become more important with the discovery that both DHEA and DHEAS are produced in the brain independently and are not influenced by factors that control adrenal DHEA secretion.54 Some reports have

ADVERSE EFFECTS AND POTENTIAL LIMITATIONS OF DHEA USE

In most studies, adverse effects are common but minor. They usually occur in women and are due to the androgenic effects. The most common adverse effect is increased skin sebum production, leading to perceived “greasiness” and acne.172 However, many women previously reported that this change is beneficial and that before DHEA replacement their skin was excessively dry. This effect is reversible when DHEA is withdrawn.

Of greater concern are the reports of mild elevations in serum transaminase

AVAILABILITY OF DHEA IN THE UNITED STATES

The International Olympic Committee banned DHEA use because of its conversion to sex hormones and thus its potential to be used as a drug of abuse. The Food and Drug Administration also banned the substance until the passage of the Dietary and Supplement Health and Education Act of 1994, when this ruling was overturned. DHEA is now freely available in pharmacies and health food stores, where it is classified as a food supplement. This is despite the fact that DHEA is not a food, that DHEA does

SUMMARY AND CONCLUSIONS

DHEA and DHEAS are intriguing hormones. Their metabolites have a variety of effects on several physiological systems, and yet little is known about the role of either DHEA or DHEAS in normal physiology. It is still unclear whether aging should be classified as a DHEA-deficient state. In hypoadrenal subjects, DHEA deficiency is associated with a lower quality of life. However, these hormones are not essential for life because hypoadrenal subjects and those who have undergone adrenalectomy who

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