Since an increase in tumor necrosis factor alpha (TNF alpha) expression has been associated with insulin resistance, this study was undertaken to determine the status of circulating TNF alpha and the relationship of TNF alpha with insulin levels, body weight, or both in women with polycystic ovary syndrome (PCOS). Fasting serum samples were analyzed in 34 subjects with PCOS, of whom 22 were obese (body mass index [BMI] >27 kg/m(2)), and in 40 normal control women, of whom 20 were obese. Women with PCOS exhibited a significantly (P < .02) higher mean serum TNF alpha concentration compared with the controls. The serum TNF alpha lever and BMI were directly correlated in women with PCOS (r = .48, P < .005) and highly correlated in controls (r = .78, P < .001). When subjects were classified by body weight, the mean serum TNF alpha concentration was significantly (P < .001) elevated in normal-weight women with PCOS compared with normal-weight controls. On the other hand, mean serum TNF alpha concentrations in obese women with PCOS and obese controls were similar and significantly (P < .02) higher than in normal-weight women with PCOS. A direct correlation between serum fasting insulin and TNF alpha was evident in controls (r = .35, P < .03), but not in women with PCOS. However, in the subgroup of obese women with PCOS, fasting insulin directly correlated (r = .49, P < .03) with TNFa and the median fasting serum insulin concentration was significantly (P <.05) higher compared with the level in normal-weight women with PCOS and all controls. Fasting insulin and TNF alpha were no longer correlated in controls as a group and in obese women with PCOS when controlling for body weight. Serum TNF alpha did not correlate with luteinizing hormone (LH), testosterone (T), or dehydroepiandrosterone sulfate (DHEAS) in women with PCOS. However, serum insulin was significantly correlated (r = .49, P < .0004) with T and the BMI exhibited a trend for correlation with serum T (r = .33, P = .05) in women with PCOS. Finally, the mean serum LH concentration was significantly (P < .02) higher in normal-weight women with PCOS versus obese women with PCOS, and serum LH levels exhibited a trend for an inverse correlation with the BMI (r = .31, P = .09) in women with PCOS. We conclude that (1) serum TNF alpha is increased in normal-weight women with PCOS and is even higher in obese individuals regardless of whether they have PCOS; (2) factors other than obesity are the cause of elevated serum TNF alpha in normal-weight women with PCOS; and (3) whereas increased circulating TNF alpha may mediate insulin resistance in obesity, which may in turn promote hyperandrogenism in obese women with PCOS, it remains to be demonstrated whether this is also the case in normal-weight women with PCOS. Copyright (C) 1999 by W.B. Saunders Company.
