Lack of effect of dehydroepiandrosterone in obese men.

To assess the effects of dehydroepiandrosterone (DHEA) on weight and body fat mass in young obese men, six obese (body mass index, 31.5 +/- 2.9 (s.e.] men were studied at baseline, after 28 days of placebo administration, and again after 28 days of DHEA (1600 mg/day) administration. Body fat mass was assessed on each occasion by three separate methods: hydrostatic weighing, impedance plethysmography, and skinfold measurements at four body sites. Waist-to-hip ratios were recorded. In addition, tissue sensitivity to insulin was determined using the modified minimal model technique, and serum lipids were assayed. Serum DHEA-sulfate levels rose from 7.4 +/- 1.7 mumol/l at baseline to 39.8 +/- 11.9 mumol/l after DHEA administration (P less than 0.05). Although body fat mass was reduced in two of the six men following DHEA administration, for the group as a whole neither total body weight, body fat mass, or waist-to-hip ratio changed significantly during the study. No change in either tissue insulin sensitivity or serum lipids was observed. These observations suggest that, at a daily dose of 13.4-19.7 mg/kg, short-term DHEA administration does not affect the total weight, body fat mass, fat distribution, insulin sensitivity, or lipid status of obese young men.

Suppression of serum dehydroepiandrosterone sulfate levels by insulin: an evaluation of possible mechanisms.

We previously demonstrated a progressive decline in serum dehydroepiandrosterone sulfate (DHEA-S) levels in women during a hyperinsulinemic-euglycemic clamp. To determine whether this fall in serum DHEA-S levels might have been due to insulin-stimulated 1) hydrolysis of DHEA-S to dehydroepiandrosterone (DHEA), 2) conversion of DHEA-S/DHEA to androstenedione, and/or 3) urinary excretion of these steroids, 10 additional men were studied by the hyperinsulinemic-euglycemic clamp technique. Each man received a 0.1 U/kg (0.72 nmol/kg) insulin bolus dose, followed by a 10 mU/kg.min (72 pmol/kg.min) insulin infusion for 4 h. An average insulin level of 12,390 +/- 259 (+/- SE) pmol/L (1,726.8 +/- 36 microU/mL) was achieved; serum glucose was maintained at 5.0 +/- 0.1 mmol/L (90.5 +/- 2.3 mg/dL). During the hyperinsulinemia, serum DHEA-S levels fell progressively and were significantly lower than baseline at 4 and 6 h of study (85.5 +/- 5.9% and 79.1 +/- 3.2% of baseline values, respectively; P less than 0.05). Serum DHEA levels fell concurrently and were significantly lower than baseline at 2, 4, and 6 h of study (66.2 +/- 12.3%, 61.6 +/- 11.2%, and 52.9 +/- 10.2% of baseline values, respectively; P less than 0.05). The percent fall in serum DHEA levels correlated positively with the percent fall in serum DHEA-S levels (r = 0.44; P less than 0.02). Serum androstenedione levels also fell progressively during hyperinsulinemia and were significantly lower than baseline at 2, 4, and 6 h of study (71.5 +/- 4.1%, 71.0 +/- 7.2%, and 48.1 +/- 3.3% of baseline values, respectively; P less than 0.05). No change in serum DHEA-S, DHEA, or androstenedione levels occurred in paired control studies, during which 0.45% saline was infused at rates matched exactly to the rates of the dextrose and insulin infusions during the hyperinsulinemic clamp studies. Despite decreasing serum DHEA-S and DHEA levels during hyperinsulinemia, urinary DHEA-S and DHEA glucuronide excretions were increased by 50% (P less than 0.05) and 86% (P = 0.05), respectively, compared to urinary excretion of these steroids during control studies. In contrast, urinary excretion of unconjugated DHEA was unchanged. Quantitatively, however, increased urinary excretion of conjugated DHEA during hyperinsulinemia accounted for only about 5% of the concomitant fall in serum DHEA-S concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)