To evaluate the role of TNF-α in the pathogenesis of hyperandrogenism, we have evaluated the serum TNF-α levels, as well as several polymorphisms in the promoter region of the TNF-α gene, in a group of 60 hyperandrogenic patients and 27 healthy controls matched for body mass index.
Hyperandrogenic patients presented with mildly increased serum TNF-α levels as compared with controls (mean[median] ± sd: 7.2[7.0] ± 3.3 pg/ml vs. 5.6[4.4] ± 4.0 pg/ml, P < 0.02). Although no differences in body mass index and insulin resistance indexes were observed between patients and controls, when subjects were classified by body weight, serum TNF-α was increased only in lean patients as compared with lean controls, but this difference was not statistically significant when comparing obese patients with obese controls.
The TNF-α gene polymorphisms studied here (−1196C/T, −1125G/C,− 1031T/C, −863C/A, −857C/T, −316G/A, −308G/A, −238G/A, and− 163G/A) were equally distributed in hyperandrogenic patients and controls. However, carriers of the −308A variant presented with increased basal and leuprolide-stimulated serum androgens and 17-hydroxyprogesterone levels when considering patients and controls as a group. No differences were observed in serum TNF-α levels, body mass index, and insulin resistance indexes, depending on the presence or absence of these variants.
In conclusion, our present results suggest that the TNF-α system might contribute to the pathogenesis of hyperandrogenism, independent of obesity and insulin resistance. However, elucidation of the precise mechanisms underlying the relationship between the TNF-α system and androgen excess is needed before considering TNF-α as a significant contributing factor to the development of hyperandrogenism.
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