EFFECTS OF INSULIN REDUCTION WITH BENFLUOREX ON SERUM DEHYDROEPIANDROSTERONE (DHEA), DHEA SULFATE, AND BLOOD-PRESSURE IN HYPERTENSIVE MIDDLE-AGED AND ELDERLY MEN

To determine whether a reduction in insulinemia mould be associated wi th a rise in serum dehydroepiandrosterone (DHEA) sulfate in insulin-re sistant men, 29 middle-aged (30-59 yr old) and 28 elderly (60-80 yr ol d) hypertensive men were enrolled into a single blind, placebo-control led study, in which benfluorex was administered to improve insulin sen sitivity and reduce circulating insulin. Men in each age group receive d either benfluorex (150 mg) or placebo three times daily for 6 weeks, and fasting serum insulin, glucose, DHEA, DHEA sulfate, and cortisol were determined before and after treatment. Glucose tolerance was also assessed by an oral glucose tolerance test. Benfluorex treatment lowe red diastolic and systolic blood pressures and improved glucose tolera nce in both age groups. In middle-aged men, benfluorex (n = 12) reduce d both the area under the curve for glucose (AUC(GLUCOSE); from 977 +/ - 27 to 814 +/- 27 mmol/L min; P = 0.0001) and the AUC(INSULIN) (from 78.1 +/- 7.9 to 44.5 +/- 5.7 nmol/L.min; P < 0.0001) during the oral g lucose tolerance test. In elderly men, benfluorex (n = 15) also reduce d both the AUC(GLUCOSE) (from 1100 +/- 60 to 864 +/- 26 mmol/L.min; P < 0.0001) and the AUC(INSULIN) (from 88.9 +/- 5.6 to 44.8 +/- 5.8 nmol /L.min; P < 0.0001). Concurrent with the reduction in insulinemia, ben fluorex treatment was associated with rises in both serum DHEA sulfate and unconjugated DHEA. In middle-aged men, serum DHEA sulfate and DHE A rose from 6.80 +/- 0.75 to 10.52 +/- 1.02 mu mol/L (P < 0.015) and f rom 13.69 +/- 1.95 to 22.78 +/- 2.90 nmol/L (P < 0.03), respectively. In elderly men, serum DHEA sulfate and DHEA rose from 5.16 +/- 0.67 to 8.36 +/- 1.21 mu mol/L (P < 0.015) and from 8.47 +/- 0.99 to 22.61 +/ - 3.24 nmol/L (P < 0.0005), respectively. In neither middle-aged nor e lderly men did serum cortisol change with benfluorex treatment. Neithe r glucose tolerance nor serum DHEA, DHEA sulfate, or cortisol levels c hanged in either middle-aged (n = 17) or elderly(n = 13) men treated w ith placebo. We conclude that benfluorex treatment lowers blood pressu re, improves glucose tolerance, reduces the glucose-stimulated insulin response, and increases serum DHEA and DHEA. sulfate in both middle-a ged and elderly men. These findings lend further support to the idea t hat insulin regulates DHEA and DHEA sulfate metabolism in men under ph ysiological conditions and indicates that insulin's action to reduce c irculating DHEA and DHEA sulfate in men occurs over a broad age range (30-80 yr).