Dehydroepiandrosterone

Description
Dehydroepiandrosterone (DHEA) is a hormone produced by the adrenal gland. DHEA sulfate (DHEA-S) is synthesized from DHEA and converted into other hormones (vitacost.com). Tests measure DHEA-S instead of DHEA because DHEA-S is less rapidly cleared from the blood stream and has less diurnal variation (Kroboth et al., 1999; Longcope, 1996; Rosenfeld et al., 1971, 1975).

Production of DHEA stops at birth, then begins again around age seven and peaks when a person is in their mid-20s. From the early 30s on there is a steady decline (about 2 percent each year) until around age 75 and older when the level of DHEA in the body is about 5 percent of peak. Because DHEA-S is known to decrease with age and is related to longevity (Kalimi, & Regelson, 1999; Lopez, 1984; Roth et al., 2002; Rotter et al., 1985; Rudman et al., 1990; Thomas et al., 1994; Yen, 2001), DHEA-S has attracted attention for the possible “anti-aging” effects.

Normal values for serum DHEA-S vary with sex and age. Normal values may vary slightly among different laboratories. Normal ranges are 800-5600 mcg/l for men, 350-4300 mcg/l for women (Note: mcg/dl = microgram per deciliter).

Significance of Measurement
The level of DHEA-S is an indicator of hypothalamic-pituitary axis activity. As an individual interacts with his/her environment, the stimuli encountered can serve as challenges or stressors that elicit responses from the HPA axis as well as other internal homeostatic regulatory systems. DHEA-S has been hypothesized to serve as a functional antagonist to HPA axis activity and thus is an important indicator of overall activity in the HPA axis (Kimonides et al., 1998; Svec, & Lopez, 1989).

While there are mixed results by gender (Glei et al., 2004), the literature generally documents a positive relationship between low DHEA-S and health outcomes. Lower level of DHEA-S is related to a history of heart disease and mortality (Barrett- Connor, & Goodman-Gruen, 1995; Beer et al., 1996; Feldman et al., 1998; Jansson et al., 1998). DHEA-S is thought to be protective against heart disease because of its anticlotting and antiproliferative properties (Beer et al., 1996; Jesse et al., 1994). It is also known to be related to physical and mental functioning (Crimmins et al., 2003; Ravaglia et al., 1997; Seplaki et al., 2004). Low DHEA-S has been included as one component of allostatic load (Seeman et al., 2001, 2004). DHEA-S is one of the four primary mediators in allostatic load measures that predict mortality and secondary outcomes such as systolic and diastolic blood pressure, waist-to-hip ratio (WHR), HDL and total cholesterol and glycosylated hemoglobin (McEwen, 2000; Seeman et al. 1997). In addition, studies have found that DHEA-S is a marker for bone turnover predicting bone mineral density (Gurlek, & Gedik, 2001). Low levels have also been linked to Alzheimer’s disease (Bicikova et al., 2004).

Method of Measurement
The test can be performed on blood, saliva or urine samples.

References
· Barrett-Connor, E., & Goodman-Gruen, D. (1995). The epidemiology of DHEAS and cardiovascular disease. Annals of the New York Academy of Sciences, 774, 259-270.
· Beer, N., Jakubowicz, D.J., Matt, D.W., Beer, R.M., & Nestler, J.E. (1996). Dehydroepiandrosterone reduces plasma plasminogen activator inhibitor type I and tissue plasminogen activator antigen in men. American Journal of the Medical Sciences, 311, 205-210.
· Bicikova, M., Ripova, D., Hill, M., Jirak, R., Havlikova, H., Tallova, J., et al. (2004). Plasma levels of 7-hydroxylated dehydroepiandrosterone (DHEA) metabolites and selected amino-thiols as discriminatory tools of Alzheimer’s disease and vascular dementia. Clinical Chemistry and Laboratory Medicine, 42(5), 518-524.
· Crimmins, E.M., Johnston, M., Hayward, M., & Seeman, T. (2003). Age differences in allostatic load: An index of physiological dysregulation. Experimental Gerontology, 38, 731-734.
· Feldman, H., Johannes, C., McKinlay, J., & Longcope, C. (1998). Low dehydroepiandrosterone sulfate and heart disease in middle-aged men: Cross-sectional results from the Massachusetts Male Aging Study. Annals of Epidemiology, 8, 217-228.
· Glei, D., Goldman, N., Weinstein, M., & Liu, I. (2004). Dehydroepiandrosterone sulfate (DHEAS) and health: Does the relationship differ by sex. Experimental Gerontology, 39, 321-331.
· Gurlek, A., & Gedik, O. (2001). Endogenous sex steroid, GH and IGF-I levels in normal elderly men: Relationships with bone mineral density and markers of bone turnover. Journal of Endocrinological Investigation, 24(6), 408-414.
· Jansson, J.H., Nilsson, T.K., & Johnson, O. (1998). von Willebrand factor, tissue plasminogen activator, and dehydroepiandrosterone sulphate predict cardiovascular death in a 10 year follow up of survivors of acute myocardial infarction. Heart, 80(4), 334-337.
· Jesse, R.L., Loesser, K., Eich, D.M., Qian, Y.Z., Hess, M.L., & Nestler, J.E. (1994). Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Annals of the New York Academy of Sciences, 774, 281-290.
· Kalimi, M., & Regelson, W. (Eds.). (1999). Dehydroepiandrosterone (DHEA): Biochemical, physiological, and clinical aspects. New York: Walter de Gruyter, Inc.
· Kimonides, V., Khatibi, N., Sofroniew, M., & Herbert, J. (1998). Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 95, 1852-1857.
· Kroboth, P.D., Salek, F.S., Pittenger, A.L., Fabian, T.J., & Frye, R.F. (1999). DHEA and DHEAS: A review. Journal of Clinical Pharmacology, 39, 327–348.
· Longcope, C. (1996). Dehydroepiandrosterone metabolism. Journal of Endocrinology, 150, S107–S118.
· Lopez, S.A. (1984). Metabolic and endocrine factors in aging. In H. Rothschild (Ed.), Risk Factors for Senility (pp. 205-219). New York: Oxford University Press.
· McEwen, B. (2000). Allostasis and allostatic load: Implications for neuropsychopharmacology. Neuropsychopharmacology, 22(2), 108-124.
· Ravaglia, G., Forti, P., Maioli, F., Boschi, F., Cicognani, A., Bernardi, M., et al. (1997). Determinants of functional status in healthy Italian nonagenarians and centenarians: A comprehensive functional assessment by the instruments of geriatric practice. Journal of the American Geriatrics Society, 45(10), 1196-1202.
· Rosenfeld, R.S., Hellman, L., Roffwarg, H., Weitzman, E.D., Fukushima, D.K., & Gallagher, T.F. (1971). Dehydroepiandrosterone is secreted episodically and synchronously with cortisol by normal man. Journal of Clinical Endocrinology and Metabolism, 33, 87–92.
· Rosenfeld, R.S., Rosenberg, B.J., Fukushima, D.K., & Hellman, L. (1975). 24-hour secretory pattern of dehydroepiandrosterone and dehydroepiandrosterone sulfate. Journal of Clinical Endocrinology and Metabolism, 40, 850–855.
· Roth, G.S., Lane, M.A., Ingram, D.K., Mattison, J.A., Elahi, D., Tobin, J.D., et al. (2002). Biomarkers of caloric restriction may predict longevity in humans. Science, 297, 811.
· Rotter, J.I., Wong, F.L., Lifrak, E.T., & Parker, L.N. (1985). A genetic component to the variation of dehydroepiandrosterone. Metabolism, 34(8), 731–736.
· Rudman, D., Shetty, K.R., & Mattson, D.E. (1990). Plasma dehydroepiandrosterone sulfate in nursing home men. Journal of the American Geriatrics Society, 38, 421–427.
· Seeman, T., Glei, D., Goldman, N., Weinstein, M., Singer, B., & Lin, Y.-H. (2004). Social relationships and allostatic load in Taiwanese elderly and near elderly. Social Science and Medicine, 59, 2245-2257.
· Seeman, T., McEwen, B.S., Rowe, J.W., & Singer, B.H. (2001). Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. Proceedings of the National Academy of Sciences of the United States of America, 98(8), 4770-4775.
· Seeman, T.E., Singer, B.H., Rowe, J.W., Horwitz, R.I., & McEwen B.S. (1997) Price of adaptation—allostatic load and its health consequences: MacArthur studies of successful aging. Archives of Internal Medicine, 157, 2259–2268.
· Seplaki, C., Goldman, N., Weinstein, M., & Lin, Y.-H. (2004). How are biomarkers related to physical and mental well-being? Journal of Gerontology: Biological Sciences, 59, B201-B217.
· Svec, S., & Lopez, A. (1989). Antiglucocorticoid actions of dehydroepiandrosterone and low concentrations in Alzheimer’s disease. Lancet, 2, 1335-1336.
· Thomas, G., Frenoy, N., Legrain, S., Sebag-Lanoe, R., Baulieu, E.E., Debuire, B. (1994). Serum dehydroepiandrosterone sulfate levels as an individual marker. Journal of Clinical Endocrinology and Metabolism, 79, 1273–1276.
· Yen, S.S.C. (2001). Dehydroepiandrosterone sulfate and longevity: new clues for an old friend. Proceedings of the National Academy of Sciences of the United States of America, 98(15), 8167–8169.