Skeletal system

Possible effects of DHEA on bone mineral density and bone markers have been of considerable interest, as sex steroids have been demonstrated to influence bone remodeling and to prevent osteoporosis. However, small sample size and short duration of treatment precluded clear conclusions in many trials. Moreover, only randomized placebo-controlled trials allow a robust assessment of the effects of DHEA on bone. Some open label studies have reported increases in bone mineral density (BMD) (Labrie et al. 1997; Villareal et al. 2000) whereas in placebo-controlled trials DHEA failed to affect BMD or bone markers (Kahn and Halloran 2002; Morales etal. 1998; Yen etal. 1995). In the DHEAge study (Baulieu etal. 2000) some increases in BMD were found in women (<70 years of age) at the femoral neck. However, no effects were observed in men. This finding is in keeping with preliminary results from patients with primary adrenal insufficiency (Gurnell et al. 2002) reporting also an increase in femoral neck BMD as assessed by DXA. DHEA effects on bone markers were missing in men (Arlt etal. 2001; Baulieu etal. 2000; Kahn and Halloran 2002) and variable in women with either increases, decreases or no change in bone resorption markers (Baulieu et al. 2000; Callies et al. 2001; Villareal etal. 2000) and increases or no change in osteocalcin (Baulieu etal. 2000; Callies etal. 2001).

At present it seems likely that beneficial effects of DHEA on BMD are small and restricted to women, possibly due to androgenic biotransformation of DHEA. However, only large prospective controlled trials will settle this issue.

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