What is DHEA? DHEA is a steroid hormone primarily made from cholesterol in the adrenal glands. The remaining DHEA production comes from the ovaries and hydrolysis of DHEAS. DHEAS is primarily produced in the adrenal glands. DHEA and DHEAS are thought to be by-products of other hormone biosynthesis or major precursors of 17-ketosteroids. The natural function of DHEA remains unclear. Its role in human metabolism is wide spread. Its effect may have more to do with its metabolites than its native form. It is not a typical hormone because its receptor (if there is one) has not yet been found. • Fetuses produce copious amounts, but the levels drop precipitously at birth. • DHEA increases again at 6-7 years of age and peaks in the mid 20s, and then gradually declines. • At its peak DHEA is the most abundant hormone in the circulation • By the mid 60s, DHEA has dropped to 10-20% of the peak value. What causes DHEA to drop? • Illness including rheumatoid arthritis • Major depression • Periods of stress What raises DHEA? Smoking and alcohol consumption What is the role of DHEA? DHEA is supposed to slow down aging, burn fat, build muscle mass, strengthen the immune system, treat lupus and help prevent heart disease, cancer, diabetes, and Alzheimer's and Parkinson's diseases. It is also reported to increase libido, alleviate depression and increase general feelings of strength, stamina, and well being. It is generally self-prescribed as an antidote to the general effects of aging, especially around menopause. A decrease in DHEA is accompanied by reduction levels of other steroids, including testosterone and androstenedione The steroid that correlates best with chronological age and age-related cognitive and physical deficits is bioavailable testosterone. Most testosterone is tightly bond to globulins. If loosely bond, it is available for tissue use. • DHEA plays a role in binding globulins by changing their shape and increasing the binding affinity to testosterone, thus decreasing free testosterone. • Moderate levels of DHEA raises DHEA levels to youthful levels, but does not decrease the tight binding of testosterone • High levels of oral DHEA decrease loose binding of testosterone • Intramuscular administration of testosterone along with moderate doses of DHEA may restore both loose binding of testosterone and DHEA to peak levels. Mechanism of Action DHEA's mechanism of action is unknown. Patients whose adrenal glands have been removed require supplemental corticosteroids, but not DHEA. Clinical Studies • Most studies have been on animals- which show promise in preventing cancer, diabetes, heart disease, viral infection, and brain diseases • Yet, only man and a few primates synthesize and secrete DHEA and DHEAS.(3) • DHEA supplementation has not been studied and data from clinical trials is virtually nonexistent. Therefore, the safety and efficacy of DHEA has not been determined.(2) Studies have shown DHEA-induced sense of well being, a potential of free insulin--like growth factor, increases in NK cell activity and interleukin-2, cytosine involvement in maintenance of immune function, decrease in joint pain, sleep improvement, reduction in depression, and the severity of lupus.(1) Formulation and Dosage • Oral administration of 25-50mg DHEA daily will return most people's DHEA levels to their youthful peaks. • Optimal dosages are difficult to determine- healthy people of similar age have DHEA levels that vary. There is no correlation between these levels and overall health or life expectancy. • DHEA is often sold in precursor form (plant extracts-wild yams and soy). Humans have no metabolic pathway to accomplish this long, complex synthesis, making it unlikely that these products affect blood DHEA levels.(3) • DHEA is available without a prescription. Men can safely take up to 50mg/day; women should not take more than 25mg/day. Positive effects have been noted at doses as low as 5 mg/day.(2) Route of Administration The hepatic biotransformation to testosterone and possibly adverse lipoprotein effects have lead to alternate ways of giving DHEA. Vaginal equivalent doses of micronized DHEA have been given, as well as sublingual and transdermal dosing.(1) Adverse Effects • Some women taking DHEA stop menstruating, grow body and facial hair and develop deeper voices.(1) Other possible signs may be hair loss on the head, weight gain at the waist and acne. • Men may show signs of excess testosterone such at sexual aggressiveness, testicular hypertrophy, aggressive tendencies, male pattern baldness, and high blood pressure • High doses may inhibit the body's natural ability to synthesize DHEA and be heptaotoxic.(2) Recommendations • It is untimely to recommend using DHEA supplements for relief of menopausal symptoms. Short- term use does seem to improve people's well being; yet DHEA is associated with many metabolic processes. The chances for adverse effects remain high. The results of larger, long-term studies are needed before evidence based recommendations can be made.(3) • If a patient wants to continue using DHEA, suggest the following steps: 1. Advise her to reduce the dose to 50mg/day 2. Monitor liver function tests frequently. 3. Monitor lipoprotein profiles frequently. 4. Check serum testosterone regularly and do not use testosterone in her HRT plan.(1) Warnings/ Contraindication/Precautions • DHEA is a precursor of estrogen and testosterone- patients with hormone sensitive cancers (breast, prostate, ovarian, and testicular) should avoid taking DHEA. • DHEA is not recommended for people under 40 years of age unless the DHEA level is know to be low (<130mg/dl in women and <180 mg/dI in men) The international Olympic Committee and the National Football League have banned the use of DHEA because it's effects resemble other anabolic steroids.(2) Judy Fichter, RNC, WHNP, 1/2000 References 1. Casson, P.R.,M.D., and Buster, J.E., M.D. (1997). DHEA replacement after menopause: HRT 2000 or nostrum of the '90s? Contemporary Nurse Practitioner Fall pp. 14-20. Upjohn Company, Kalamazoo, MI. 2. Dehydroepiandrosterone (DHEA). Integrative Medicine Access. Chestnut St., Newton, MA 3. O'Mathuna, D. P., Ph.D. DHEA supplementation during menopause. Alternative Medicine Alert, 1999, pp. 113-116.