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Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) are the most abundant steroids produced by the human adrenal gland. DHEA-S, sometimes considered as a plasma "reservoir" for the hormone, appears in the circulation at about one thousand times the concentration of DHEA, is water soluble, and is capable of being bound to albumin. Although it is DHEA that has been identified as having biological activity, the cellular receptor for, and molecular mode of action of, DHEA and DHEA-S remains uncertain. Depending upon the species and tissue, the possibilities for the former seem to include the NMDA sigma receptor, the GABAA receptor, the estrogen receptor, and the PPAR alpha receptor. In addition, and further complicating the situation, is the possibility that DHEA and DHEA-S work indirectly on target tissues, either following conversion into more potent steroids (including estrogen and testosterone), through another mediator, or as an antagonist to still another potent steroid, cortisol.

DHEA and DHEA-S are synthesized in large amounts by the fetal adrenal gland, with the levels dropping dramatically in newborn and in children. Beginning in about middle -adolescence, and coincident with the development of the zona reticularis in the adrenal cortex, the levels begin to rise sharply again. This onset of heightened activity of the adrenal gland is referred to as adrenarche. At about puberty, the blood hormone levels in boys and girls are similar; thereafter the serum concentration in males begins to exceed that of females. In both sexes, the levels of circulating DHEA and DHEA-S reach their peak during young adult life. Subsequently, in humans and other higher primates, the levels of DHEA and DHEA-S undergo, on average, a steady decline with advancing age. In humans, this decline in circulating hormone reaches about 30 percent of young adult levels by about age 65 years and about 10 percent by age 85 and older. The reduction in DHEA/DHEA-S is thought to result, at least in part, from an involution of the zona reticularis. The latter, age-associated change in adrenal gland structure and DHEA production is referred to as adrenopause.

In spite of the substantial individual-to-individual variation in hormone levels, the progressive decline of these levels with age has led to consideration of DHEA and DHEA-S as biomarkers of the aging process; that is, as chemical indicators useful in tracking age-related senescent change, morbidity, and mortality. More importantly, the decline in levels of these two closely related steroids has also been implicated as being responsible, at least in part, for many of the senescent changes seen in advanced-aged individuals and in individuals with chronic illness. These changes include, but are not limited to, body composition, some forms of cancer, type II diabetes, atherosclerosis and ischemic heart disease. At least some of these associations are sex specific, though not always in a readily understood manner. For example, DHEA-S appears to be related to body composition (fat and lean body mass) in men but not in women. On the other hand, a similar association of DHEA to body composition may be present in women (17). Whatever the limitations and contradictions in the existing literature, it is the notion that diminished hormone levels in older persons are causally linked to age-related functional decline and structural change that has provided the rationale for the well-promoted use of DHEA as an "anti-aging" intervention. In the United States, DHEA is readily available without prescription. However, clinical data documenting the usefulness of DHEA supplementation in humans is limited to very few examples. As of 2001, most of the impressive findings reported on the effects of DHEA treatment have come from studies in rodent models of aging and senescent change; not from human subjects.

Systemic lupus erythematosus (SLE) appears to be one circumstance where taking DHEA benefits the patient. Using the steroid has been reported to reduce the symptoms of SLE and to permit lowering the dose of corticosteroid used to treat the disease. The latter is important because of the potential negative side effects associated with the chronic use of corticosteroids. DHEA may also be useful in the treatment of major depression. Barrett-Conner et al. (1995) found endogenous DHEA-S levels to be significantly and inversely associated with depressed mood. This finding compliments an earlier report that modest doses of DHEA over four weeks improves depression ratings in patients with major depression and low plasma DHEA-S values.

Even though hormone replacement seems a rational approach for ameliorating the possible negative consequences of naturally occurring, age-related declines in hormone levels, the only circumstance in which there is clear documentation supporting such a strategy is estrogen replacement in postmenopausal women. Even here, however, the approach remains controversial because of the risk of increasing the incidence of cancer in estrogen sensitive tissues. The justification for using DHEA in hormone replacement is (as of 2001) much weaker, with the prevailing view being that more long-term, carefully controlled, and larger clinical trials are needed before such action can be justified. In particular, more work is needed to confirm those special circumstances where initial findings are promising, such as the treatment of major depression. In addition, there appears to be growing support for the idea of using DHEA to help mitigate the negative side effects of corticosteroids (e.g., prednisone) in patients where the latter are an essential part of therapy (e.g., for chronic inflammatory disease and SLE). Thus, while no compelling reasons can be found for recommending DHEA supplementation to the healthy elderly, there may well be clinical circumstances where such supplementation will ultimately prove of significant value.

Arnold Khan

See also Androgens; Estrogen; Life Span Extension; Nutrition, Dietary Supplements.


Abbasi, A.; Duthie, E. H., JR.; Sheldahl, L.; Wilson, C.; Sasse, E.; Rudman, I.; and Mattson, D. E. "Association of Dehydroepiandrosterone Sulfate, Body Composition, and Physical Fitness in Independent Community-Dwelling Older Men and Women." Journal of the American Geriatrics Society 46 (1998): 263 273.

Barrett-Connor, E.; von Muhlen, D.; Laughlin, G. A.; and Kripke, A. "Endogenous Levels of Dehydroepiandrosterone Sulfate, But Not Other Sex Hormones, Are Associated with Depressed Mood in Older Women: The Rancho Bernardo Study." Journal of the American Geriatrics Society 47 (1999): 685691.

Ebeling, P., and Koivisto, V. A. "Physiological Importance of Dehydroepiandrosterone." Lancet 343 (1994): 14791481.

Hinson, J.P., and Raven, P. W. "DHEA Deficiency Syndrome: A New Term for Old Age?" Journal of Endocrinology. 163 (1999): 15.

Lane, M.; Ingram, D. K.; Ball, S. S.; and Roth, G. S. "Dehydroepiandrosterone Sulfate: A Biomarker of Primate Aging Slowed by Calorie Restriction." Journal of Clinical Endocrinology and Metabolism 82 (1997): 20932097.

Parker, C.R. JR. "Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate Production in the Human Adrenal During Development and Aging." Steroids 64 (1999): 640647.

van VollenhOven, R. F.; Morabito, L. M.; Engelman, E.G.; and McGuire, J. L. "Treatment of Systemic Lupus Erythematosus with Dehydroepiandrosterone: 50 Patients Treated Up to 12 Months." Journal of Rheumatology 25 (1998): 285289.

Watson, R.R.; Huls, A.; Araghinikuam, M.; and Chung, S. "Dehydroepiandrosterone and Diseases of Aging." Drugs and Aging (October 9, 1996): 274291.

Yen, S. S., and Laughlin, G. A. "Aging and the Adrenal Cortex." Experimental Gerontology 33 (1998): 897910.

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DHEA is the acronym for dehydroepiandrosterone, a hormone produced naturally from cholesterol in the adrenal glands of males and females. It is a precursor to the male sex hormone testosterone. It is also sold as an over-the-counter dietary supplement.

The human body produces very little DHEA until about the age of seven, when production soars. It peaks in the mid-20s and starts to decline in the early 30s. By the mid-70s, DHEA production has dropped by about 80-90%. At all ages, DHEA levels are slightly higher in men than women. The optimum DHEA level in a healthy adult is 750-1,250 milligrams per deciliter of blood (mg/dL) for men and 550-980 mg/dL for women.

DHEA was first identified in 1934 and was sold over the counter mainly as a weight loss aid until the late 1980s. Then the federal Food and Drug Administration (FDA) classified DHEA as a drug, making it available by prescription only. The FDA reversed itself in 1994, reclassifying DHEA as a dietary supplement obtainable without a prescription.

A 1994 study by researchers at the University of California, San Diego looked at 30 middle-age men and women who took 50 mg of DHEA a day for three months. The test subjects generally reported an improved sense of well-being, increased energy, enhanced sex drive, and an improved ability to deal with stress . The results were widely reported by the mass media, with several referring to DHEA as the "fountain of youth hormone."

Despite hundreds of studies of DHEA over the past three decades, researchers are still unclear on how the hormone works or exactly what it does in the body. Although it is know DHEA decreases with age, it is not known whether this constitutes a deficiency or is because the body needs less DHEA as it ages.

The main reason so little is known about DHEA is because the hormone is not patentable, so drug companies are unwilling to spend money doing further research on it. Much of the research today in funded through universities and the National Institute on Aging that maintains a skeptical philosophy about DHEA supplementation.

General use

Originally marketed as a weight loss supplement, DHEA is now promoted as being beneficial for treating a wide variety of medical conditions, including cancer, heart disease , Alzheimer's, and AIDS . It is also purported to have anti-aging qualities. Studies in rodents and test tubes have shown daily doses of DHEA can prevent or benefit such conditions as cancer, heart disease, osteoporosis , diabetes, lupus, obesity , and viral infections . Far fewer long-term studies have been done in humans and the results are often conflicting. In general, DHEA supplementation seems to be more beneficial to men than women.

Proponents of DHEA also say the hormone has anti-aging properties that can slow the aging process and lead to longer life. In his book, The DHEA Breakthrough: Look Younger, Live Longer, Feel Better, biochemist Stephen Cherniske, states that DHEA supplementation along with proper diet, vitamins, and exercise , can prolong life. "After all, the human body is designed to last about 120 years, and with proper care they can all be vibrantly healthy years. What DHEA provides is the missing link in your longevity program. It gives you a better-than-fighting chance against the diseases that cause more than 75 percent of premature deaths."


Most DHEA is derived from Mexican wild yams through a chemical process. Eating the yams will not produce the hormone. DHEA is generally taken once daily. Dosage recommendations vary. Allopathic physicians who support DHEA supplementation usually recommend 5-10 milligrams (mg) once a day. Some homeopathic health practitioners recommend 10-50 mg a day. Dr. Ray Sahelian, a physician and author of several books on dietary supplements, also recommends "hormone holidays." With this approach, persons would take DHEA every other day, five days in a row and two days off, or go off it one or two weeks a month. DHEA commonly is sold in tablets of 5mg, 10mg, 25mg, and 50mg. It also comes in available as a cream, ointment, lozenge, and herbal tea. A bottle of 90 25-mg capsules costs $12-24.


Several studies have shown DHEA may increase the risks of prostate cancer in men and endometrial cancer in women. Medical experts suggest before taking DHEA supplements, individuals should have a blood test to determine existing DHEA and other hormone (testosterone or estrogen) levels. Also, men taking the supplement should have regular PSA tests and women should have periodic mammograms since DHEA may promote the growth of breast cancer .

There are several warnings associated with DHEA use. It should not be taken by men who have a history of prostate problems or by women with a history of breast, ovarian, or uterine cancer . It is not recommended for anyone under age 40, or by women who are pregnant, nursing, or who can still bear children. Women who are taking an estrogen replacement, who have a history of heart disease, and anyone with other significant health problems should consult their doctor before taking DHEA.

Side effects

Some side effects have been reported and are usually associated with doses of 5 mg a day or more. These include acne , body and facial hair growth in women, enlarged breasts in men, scalp hair loss, anxiety, insomnia , headaches, mood changes, and fatigue . It can cause menstrual irregularities in women under age 50, and may decrease HDL (good cholesterol) in women. A few cases of irregular heart rhythm have been reported in people taking 25-50 mg a day of DHEA.


DHEA functions similarly to pregnenolone, so the two should not be taken together in full doses.



Cherniske, Stephen A. The DHEA Breakthrough: Look Younger, Live Longer, Feel Better. New York: Ballantine Books, 1998.

Greenberg, Beverly. DHEA Discovery: Wonder Hormone of the '90s. Los Angeles: Majesty Press, 1997.

Ley, Beth M. DHEA: Unlocking the Secrets to the Fountain of Youth. Newport Beach, CA: BL Publications, 1997.

Moore, Neecie. Bountiful Health, Boundless Energy, Brilliant Youth: The Facts About DHEA. Seattle: Validation Press. 2000.

Sahelian, Ray. All About DHEA: Frequently Asked Questions. New York: Avery Publishing Group, 1999.

Watson, Ronald Ross, ed. Health Promotion and Aging: Dehydroepiandrosterone (DHEA). Newark, NJ: Harwood Academic Publishing, 1999.


Firshein, Richard. "On the DHEA Watch." Psychology Today (November/December 1998): 24.

Marandino, Cristin. "Is Time Running Out for Longevity Supplements?" Vegetarian Times (October 1997): 20-21.

Miller, Richard A. "Lifelong Treatment With Oral DHEA Does Not Preserve Immune Function, Prevent Disease, or Improve Survival in Genetically Heterogeneous Mice." The Journal of the American Medical Association (October 6, 1999): 1,212.

Russell, Dr. Robert. "Should You Start Taking Over-the-Counter Hormones? A Closer Look at DHEA and Melatonin." Tufts University Health & Nutrition Newsletter (July 1997): 4-5.

Sadovsky, Richard. "Dehydroepiandrosterone Replacement in Older Patients." American Family Physician (October 1, 1999): 1,538.

Sahalian, Ray. "DHEA & Other Hormones .. An Update." Better Nutrition (March 1999): 66.

Sahalian, Ray. "DHEA: The Promise of Hormones." Better Nutrition (May 1998): 58-61.

Silberman, Alex. "Forever Young?" Vegetarian Times (February 2000): 66.


"Should I Take DHEA?" (2000).

Ken R. Wells

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dehydroepiandrosterone (DHEA) (dee-hy-droh-epi-an-dros-ter-ohn) n. a weak androgen produced and secreted by the adrenal glands after adrenal maturation (see adrenarche). It is largely converted to dehydroepiandrosterone sulphate and androstenedione. All three of these molecules can cause a degree of mild androgenization but can also be converted in the circulation to the more potent androgens testosterone and dihydrotestosterone.

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"dehydroepiandrosterone." A Dictionary of Nursing. . 15 Dec. 2017 <>.

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