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TNF- and Hyperandrogenism: A Clinical, Biochemical, and Molecular Genetic Study

Departments of Endocrinology (H.F.E.-M., R.M.C., J.S.) and Molecular Genetics (J.L.S.M.), Hospital Ramón y Cajal, 28034 Madrid, Spain

Address all correspondence and requests for reprints to: Héctor F. Escobar-Morreale, M.D., Ph.D., Department of Endocrinology, Hospital Ramón y Cajal, Carretera de Colmenar km. 9,100, 28034 Madrid, Spain. E-mail: hector.escobar{at}uam.es

Abstract

To evaluate the role of TNF- in the pathogenesis of hyperandrogenism, we have evaluated the serum TNF- levels, as well as several polymorphisms in the promoter region of the TNF- 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- 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- 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- 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- 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- 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- system and androgen excess is needed before considering TNF- as a significant contributing factor to the development of hyperandrogenism.

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