Figure XX. Synthetic Pathway of DHEA, Testosterone and Estradiol P450c17 Pregnenolone 17 Hydroxy Pregnenolone DHEA Testosterone Estradio (E2) Estrogen Cholesterol P450scc Androsteridione 3 Beta-Hydroxysteroid Dehydrogenase Figure XX. Synthetic Pathway of DHEA, Testosterone and Estradiol DHEA is a native, cholesterol-derived androgen precursor. The primary metabolic pathway is shown in Figure (XX). Oral dietary supplements have been shown to increase serum DHEA levels as well as levels of downstream androgens (Kohut, et al 2003). This increase in androgens is foundation for the purported anti-aging, improved immune response, increased libdo, etc. of dietary supplements. Much of the interest and hype regarding DHEA assumes that the lack of DHEA causes many of the symptoms of aging (Feldman, et al 2002). Much of the research has tested the cause-and-effect relationships between DHEA and the symptoms of aging. One important consideration when evaluating potential effects of DHEA supplements is that animal have limited applicability to humans, as the sources of androgens varies by species (Kohut, et al 2003). The immune effects, although present in vitro and in mice, were not exhibited in otherwise healthy men (Kohut, et al 2003). Erectile dysfunction was demonstrated to be unaffected by DHEA serum levels and supplementation (Tomova, Kumanov 2004). The side effects of DHEA are similar to androgen agonists and replacements, including the development of the secondary sex characteristics of the opposite gender (Williams, Lempke 2002). Both genders may also experience electrolyte retention (Williams, Lempke 2002). http://www.emedicine.com/PED/topic1051.htm Serum Levels of Pregnenolone and 17-hydroxypregnenolone in Patients withRheumatoid Arthritis and Systemic Lupus Erythematosus: Relation to Other Adrenal Hormones Vogl, Falk, Dorner, Scholmerich, Straub, The Journal of Rheumatology 2003 30:2 Conversion of pregnenolone to DHEA by human 17 alpha-hydroxylase/17,20-lyase(P450c17) Soucy, Luu-The, European Journal of Biochemistry, 2000 267 Ingestion of a Dietary Supplement Containing Dehydroepiandrosterone (DHEA) and Androstenedione Has Minimal Effect on Immune Function in Middle-Aged Men Kohut, et al. JOunrla of the American College of Nutrition 2003 22:5 Williams, D, Lemke, T, Foye’s Principles of Medicinal Chemistry, 5th edition. 2002 Lippincott Williams and Wilkins Tomova, A, Kumanov, P. Are dehydroepiandrosterone sulphate and lipids associated with erectile dysfunction? Maturitas 2004 50:294-299 Feldman, H.A., et al. Age trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results from the Massachusetts Male Aging Study. The Journal of Clinical Endocrinology & Metabolism 2002: 87(2)