Dehydroepiandrosterone (DHEA) administration has been shown to reduce
accumulation of abdominal visceral fat and protect against insulin resistance
in laboratory animals, but it is not known whether DHEA decreases abdominal
obesity in humans. DHEA is widely available as a dietary supplement without
To determine whether DHEA replacement therapy decreases abdominal fat
and improves insulin action in elderly persons.
Design and Setting
Randomized, double-blind, placebo-controlled trial conducted in a US
university-based research center from June 2001 to February 2004.
Fifty-six elderly persons (28 women and 28 men aged 71 [range, 65-78]
years) with age-related decrease in DHEA level.
Participants were randomly assigned to receive 50 mg/d of DHEA or matching
placebo for 6 months.
Main Outcome Measures
The primary outcome measures were 6-month change in visceral and subcutaneous
abdominal fat measured by magnetic resonance imaging and glucose and insulin
responses to an oral glucose tolerance test (OGTT).
Of the 56 men and women enrolled, 52 underwent follow-up evaluations.
Compliance with the intervention was 97% in the DHEA group and 95% in the
placebo group. Based on intention-to-treat analyses, DHEA therapy compared
with placebo induced significant decreases in visceral fat area (–13
cm2 vs +3 cm2, respectively; P = .001)
and subcutaneous fat (–13 cm2 vs +2 cm2, P = .003). The insulin area under the curve (AUC)
during the OGTT was significantly reduced after 6 months of DHEA therapy compared
with placebo (–1119 μU/mL per 2 hours vs +818 μU/mL per 2 hours, P = .007). Despite the lower insulin levels,
the glucose AUC was unchanged, resulting in a significant increase in an insulin
sensitivity index in response to DHEA compared with placebo (+1.4 vs –0.7, P = .005).
DHEA replacement could play a role in prevention and treatment of the
metabolic syndrome associated with abdominal obesity.