Disparate Effects of Weight Reduction By Diet On Serum DHEA-Sulfate Levels In Obese Men And Women-Authors’

We thank Dr. Remer for his thoughtful comments. For brevity’s sake we refer Dr. Remer to a recent review (1) that addresses many of the issues raised by Dr. Remer and discusses in detail why WE believe insulin may lower serum dehydroepinndrosterone (DHEA) and DHEA-sulfate in men, but not in women. This speculation is based not only on our single diet study (2) but on multiple lines of evidence and studies by several investigators. Parenthetically, it should not be surprising that insulin may influence serum DHEA-sulfate in sex-spttcific fashion, as a genetic study (3) indicates that serum DHEAsulfate is highly determined by heredity in women, whereas in men heritable factors play a minor role and the influence of other factors (perhaps insulin? ) predominate. Many, although certainly not all, cross-sectional studies suggest that serum DHEA-sulfate is higher in men than in women. However, there exists striking variation in both sexes with a range in values as great as 6-fold in any age group. The sample size in our study (2) was limited (29 women and 18 men), and the higher serum DHEA-sulfate in the women compared with men may merely represent normal biologic variation. It is not necessary to invoke an unidentified and pervasive abnormality in our ftmale subjects. Moreover, in contrast to cross-sectional studies that assessed only nonobcse individuals, we specifically examined obese and hyperinsulinemic men and ~vomen. If insulin indeed reduces serum DHEA-sulfate in men but not in women, one might fully expect serum DHEA-sulfate at baseline to be reduced in men compared with women! Our study (2) showed that although the men and women lost equivalent weight and experienced similar reductions in insulin and glucose, serum DHEAsulfate rose by 125% in men but did not change in women. This finding is consistent with the idea that insulin affects DHEA-sulfate metabolism in sexspecific fashion. We were careful to caution that “weight loss is associated with multiple metabolic alterations, and the study’s design does not permit identification of any single cause for the sex-specific change”. Dr. Remer refers to a study by Tegtlman (4), in which serum DHEAsulfate increased Lvith fasting in both men and women. We cited this study in our paper, but also noted two other studies (5,6) in which serunl DHEA-sulfate did not change with weight loss in \vomen. In contrast, studies in men appear uniformly to demonstrate a rise in serum DHEAsulfate (4, 7, X), and in one of these studies (7) serum DHEA-sulfate rose by 100V, which is of a magnitude similar to that observed by us. Finally, Dr. Remcr suggests that insulin’s effects on DHEA-sulfate may be mediated by changes in serum albumin. We cannot exclude this mechanism but regard it as unlikely. We administered either metformin (Y) or bcnfluorcx (IU) to insulin-resistant men, which improved insulin sensitivity and reduced serum insulin. Concomitantly serum DHEAsulfate and unconjugnted DHEA rose by 48-62% and hh-166%, respectively. WC are not aware that either drug alters serum albumin concentrations, and they would not be expected to do so to a degree that could account for these striking rises in serum steroids.