Elevated Serum Levels of Tumor Necrosis Factor Alpha in Normal-Weight Women With Polycystic Ovary Syndrome

Since an increase in tumor necrosis factor alpha (TNFα) expression has been associated with insulin resistance, this study was undertaken to determine the status of circulating TNFα and the relationship of TNFα 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/m2), and in 40 normal control women, of whom 20 were obese. Women with PCOS exhibited a significantly (P < .02) higher mean serum TNFα concentration compared with the controls. The serum TNFα level 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 TNFα concentration was significantly (P < .001) elevated in normal-weight women with PCOS compared with normal-weight controls. On the other hand, mean serum TNFα 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 TNFα 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 TNFα 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 TNFα were no longer correlated in controls as a group and in obese women with PCOS when controlling for body weight. Serum TNFα 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 TNFα 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 TNFα in normal-weight women with PCOS; and (3) whereas increased circulating TNFα 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.