TNF-alpha and hyperandrogenism: A clinical, biochemical, and molecular genetic study

To evaluate the role of TNF-a in the pathogenesis of hyperandrogenism, we h ave evaluated the serum TNF-a levels, as well as several polymorphisms in t he promoter region of the TNF-a gene, in a group of 60 hyperandrogenic pati ents and 27 healthy controls matched for body mass index. Hyperandrogenic patients presented with mildly increased serum TNF-a 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 in dex and insulin resistance indexes were observed between patients and contr ols, when subjects were classified by body weight, serum TNF-a was increase d 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-alpha 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 di stributed in hyperandrogenic patients and controls. However, carriers of th e -308A variant presented with increased basal and leuprolide-stimulated se rum androgens and 17-hydroxyprogesterone levels when considering patients a nd controls as a group. No differences were observed in serum TNF-alpha lev els, body mass index, and insulin resistance indexes, depending on the pres ence or absence of these variants. In conclusion, our present results suggest that the TNF-alpha system might contribute to the pathogenesis of hyperandrogenism, independent of obesity and insulin resistance. However, elucidation of the precise mechanisms unde rlying the relationship between the TNF-alpha system and androgen excess is needed before considering TNF-alpha as a significant contributing factor t o the development of hyperandrogenism.