Effects of dehydroepiandrosterone on bone mineral density: what implications for therapy?

Because dehydroepiandrosterone (DHEA) levels decline dramatically with aging and low DHEA levels correlate with age-related diseases, it has been suggested that old age may represent a condition of DHEA deficiency. Accordingly, there have been some studies of the effects of restoring the DHEA levels of older individuals back to the normal range in the young. Emerging evidence from these studies shows that prasterone (DHEA replacement) may significantly enhance bone mineral density (BMD). In fact, the improvements of BMD in response to prasterone are accompanied not only by suppression of bone resorption but more importantly, stimulation of bone formation. Thus, prasterone appears to have additional anabolic effects on the skeleton, which represents an advantage over current pharmacologic agents that only inhibit bone loss. The osteogenic effects in elderly people are consistent with DHEA serving primarily as a precursor to active androgens and estrogens in local tissues such as bone. DHEA replacement may also increase levels of insulin-like growth factor-1, which may contribute to its anabolic effects. Although prasterone may be an effective therapy for improving BMD in both sexes, there appears to be gender differences in responses with more osteogenic effects in older women compared with older men. More studies, particularly randomized, placebo-controlled trials which include fractures as an outcome, are needed to fully define the potential utility of DHEA replacement as an anabolic intervention for age-related osteoporosis. These studies would also be important to gain information on risks associated with long-term DHEA replacement therapy. Further investigations are particularly warranted because prasterone is available over-the-counter in many countries and many older individuals are taking this hormone, without medical supervision, for its purported anti-aging properties.