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The Effects of Gonadotropin Treatment on the Immunological Features of Male Patients with Idiopathic Hypogonadotropic Hypogonadism

Departments of Endocrinology and Metabolism (M.O., I.C.O.), Internal Medicine (Z.Y., I.H.K.), Hydroclimatology (M.T.), and Immunology (A.P., A.S.), Gulhane School of Medicine, 06018 Etlik-Ankara, Turkey

Address all correspondence and requests for reprints to: Metin Ozata, M.D., Department of Endocrinology and Metabolism, Gulhane School of Medicine, 06018 Etlik-Ankara, Turkey. E-mail: mozata{at}obs.gata.edu.tr

There is a significant line of evidence for a role of androgens in the modulation of the immune system. However, little is known about immunological features of male patients with idiopathic hypogonadotropic hypogonadism (IHH) and the potential effects of gonadotropin treatment. Thus, the objective of this study was to evaluate the levels of selected soluble immune parameters [IgA, IgG, IgM, C3c, C4, interleukin-2 (IL-2), and IL-4], the CD4⁺/CD8⁺ ratio, and counts of total lymphocyte and some subpopulation of lymphocytes (CD3⁺, CD4⁺, CD8⁺, and CD19⁺ cells) before and after gonadotropin treatment in men with IHH. Twenty-nine IHH patients and 19 age-matched healthy controls were included in the study. The patients were treated with human menopausal gonadotropin/hCG for 6 months.

The pretreatment levels of serum Igs, C3c, IL-2, and IL-4 in the patients were significantly higher than those in the controls (P < 0.001 for all). After treatment, all Igs (P < 0.001), C3c (P < 0.01), and IL-2 and IL-4 levels (P < 0.005) were decreased significantly compared to pretreatment levels. Pretreatment lymphocyte counts (P < 0.05); the percentages of CD3⁺ cells (P < 0.001), CD4⁺ cells (P < 0.001), and CD19⁺ cells (P < 0.001); and the CD4⁺/CD8⁺ ratio in the patient group were significantly higher (P < 0.05) than those in the controls. After treatment, the lymphocyte count (P < 0.001); CD3⁺ (P < 0.01), CD4⁺ (P < 0.001), and CD19⁺ (P < 0.005) cells; and the CD4⁺/CD8⁺ ratio (P < 0.001) were decreased, but CD8⁺ cells were increased significantly (P < 0.001).

In summary, lack of testosterone action results in the enhancement of cellular and humoral immunity. The results of this study allowed us to conclude that testosterone deficiency affects both cell-mediated and humoral immunity, and these may be modulated with gonadotropin therapy in male patients with IHH.

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