DESCRIPTION: (adapted from Investigator's abstract) Levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), the major secretory product of the adrenal gland, decrease dramatically with age, concurrent with the onset of degenerative changes and chronic diseases associated with aging. Epidemiological evidence in humans and numerous animal studies have suggested that DHEA(S) has cardioprotective, antiobesity, antidiabetic, immuno-enhancing, and cancer-preventing properties. These observations have led to the proposal that restoration of DHEA levels in older adults to those of young adults may offer protection from age-associated health deficits. To date, clinical trials of DHEA replacement have been limited due to small sample size, lack of adequate power, restriction to one gender, failure to adjust for potential confounders (baseline endogenous hormone levels and age), lack of placebo comparison groups, and short duration of administration. This double blind, placebo-controlled randomized trial will determine the acceptability, benefits, and adverse effects of 50 mg daily oral DHEA replacements for one year in 100 men and 100 women, 55 to 85 years of age, who are healthy and not currently using any hormone therapy. Data will be collected at a screening visit, baseline visit, and at three follow-up visits over the course of one year. A wide range or biological outcomes will be studied including bone mineral density and metabolism, body composition and muscle strength, immune function, and cardiovascular risk factors. Central effects of DHEA will be investigated by assessing changes in mood and well-being, cognitive function, and sexuality. Cross-sectional and longitudinal analyses comparing the treatment and placebo groups on each health outcome will be adjusted for potentially confounding covariates such as smoking, alcohol consumption, exercise, diet, and supplements and the influence of gender, age and baseline endogenous DHEA level on each outcome variable will be examined. Potential mechanisms of DHEA action will be studied including biotransformation of DHEA to active steroids and steroid metabolites, enhancement of IGF-1 bioavailability, and inhibition of IL-6 production. In addition, potential adverse effects of DHEA administration will be systematically monitored.