Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome

Since an increase in tumor necrosis factor alpha (TNF alpha) expression has been associated with insulin resistance, this study was undertaken to dete rmine the status of circulating TNF alpha and the relationship of TNF alpha with insulin levels, body weight, or both in women with polycystic ovary s yndrome (PCOS). Fasting serum samples were analyzed in 34 subjects with PCO S, of whom 22 were obese (body mass index [BMI] >27 kg/m(2)), and in 40 nor mal control women, of whom 20 were obese. Women with PCOS exhibited a signi ficantly (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 ser um TNF alpha concentration was significantly (P < .001) elevated in normal- weight women with PCOS compared with normal-weight controls. On the other h and, mean serum TNF alpha concentrations in obese women with PCOS and obese controls were similar and significantly (P < .02) higher than in normal-we ight women with PCOS. A direct correlation between serum fasting insulin an d TNF alpha was evident in controls (r = .35, P < .03), but not in women wi th PCOS. However, in the subgroup of obese women with PCOS, fasting insulin directly correlated (r = .49, P < .03) with TNFa and the median fasting se rum insulin concentration was significantly (P <.05) higher compared with t he 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 obes e women with PCOS when controlling for body weight. Serum TNF alpha did not correlate with luteinizing hormone (LH), testosterone (T), or dehydroepian drosterone sulfate (DHEAS) in women with PCOS. However, serum insulin was s ignificantly 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 L H 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 incr eased in normal-weight women with PCOS and is even higher in obese individu als regardless of whether they have PCOS; (2) factors other than obesity ar e the cause of elevated serum TNF alpha in normal-weight women with PCOS; a nd (3) whereas increased circulating TNF alpha may mediate insulin resistan ce in obesity, which may in turn promote hyperandrogenism in obese women wi th PCOS, it remains to be demonstrated whether this is also the case in nor mal-weight women with PCOS. Copyright (C) 1999 by W.B. Saunders Company.