ABSTRACT
Dehydroepiandrosterone (DHEA) is a precursor sex steroid hormone synthesized from cholesterol in the zona reticularis of the adrenal cortex, the gonads, adipose tissue, brain, and skin. Together with its sulfate version, DHEA sulfate (DHEAS), it is the most abundant steroid in humans. DHEAS, generated in the liver from the parent adrenal steroid DHEA, circulates in the blood of men in relatively huge quantities. In young people in the second and third decades of age, the highest concentrations of these steroids are observed, and gradually decrease by approximately 10% per decade (Orentreich et al. 1984). Serum DHEA steadily declines and by the age of 70 years, serum DHEA levels are approximately 20%–23% of their peak values (Davison et al. 2005; Labrie et al. 1998). The mechanism underlying this physiological decline is unknown. Consistently, in one of our previous studies we have demonstrated age-related decline in testosterone level throughout 4 years of follow-up in patients with erectile dysfunction (ED). Patients with decreasing testosterone levels were older than patients with a steady testosterone level (El-Sakka and Hassoba 2006). Therefore, this steady decrease in circulating DHEAS concentrations with age has prompted speculation that DHEA therapy might have potential bene‰ts in several diseases associated with aging. Clinical studies have also found associations between low levels of serum DHEA or DHEAS and diseases or deterioration in various physiological functions. Particularly, aging; neurological functions including decreased well-being, cognition, and memory; increased depression; aggressiveness; and
Introduction .................................................................................................................................... 351 DHEA and Underlying Mechanisms of Sexual Function .............................................................. 352
DHEA and Endothelial Function .............................................................................................. 352 DHEA and the Nitric Oxide Pathway ....................................................................................... 353 DHEA and Erectile Dysfunction ............................................................................................... 353
Testosterone and Sexual Function .................................................................................................. 354 Effect on Sexual Motivation ...................................................................................................... 354 Re‰ned Role of Androgen on Erectile Function ....................................................................... 354 Testosterone and Aging ............................................................................................................. 354 Effects of Testosterone on Ultrastructural Composition of Erectile Tissue .............................. 355
DHEA as a Treatment for Erectile Dysfunction ............................................................................ 356 Androgens and Diabetes ................................................................................................................ 357 New Insights on Androgen and Sexual Function ........................................................................... 358 Conclusions .................................................................................................................................... 359 References ...................................................................................................................................... 359
dementia have involved changes in body composition, decreased bone mineral density, obesity, diabetes, increased cardiovascular morbidity, ED, and decreased libido (Gurnell and Chatterjee 2001; Johnson, Bebb, and Sirrs 2002). Supporting this result, some trials of DHEA supplementation in healthy, middle-aged, and elderly subjects have reported improvements in different aspects of wellbeing (Morales et al. 1994).
