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The purpose of this study is to clarify the pathological and endocrinological variations of male idiopathic hypogonadotropic hypogonadism (IHH) from the viewpoint of testicular maturation. Twenty-five patients with IHH were classified into 3 groups according to the degree of germ cell maturation. The most mature germ cells in patients with severe IHH, moderate IHH and mild IHH were spermatogonia, primary spermatocytes and postmeiotic germ cells, respectively. All patients were treated with hCG alone or a combination of hMG-hCG for 1 year or more. The therapeutic efficacy of gonadotropin therapy was evaluated by findings of semen analysis, spermatogenesis and sexual maturation. The total GCI, which was expressed as the number of germ cells per Sertoli cell, diameter of the seminiferous tubules and testicular volume in mild IHH were the largest among the 3 IHH groups, and those in severe IHH were the smallest. Even in mild IHH, spermatogonial proliferation and meiotic activity were quantitatively smaller than those of normal pubertal boys. All patients showed extremely low basal testosterone levels. Response of serum testosterone to hCG administration correlated to the maturity of germ cells. Basal serum gonadotropin levels and responses to GnRH administration varied widely among the 3 groups. In particular, the response of serum gonadotropin to GnRH correlated to the maturity of the germ cells. Spermatogenesis could be initiated by hCG alone in IHH patients without cryptorchidism. Normal sperm density was obtained by hCG alone in the case of mild IHH; however, in moderate and severe IHH groups, hMG-hCG therapy was required for sufficient spermiogenesis. Sexual maturation was completely obtained by gonadotropin therapy within 1 year in moderate and mild IHH. However, in severe IHH, satisfactory sexual maturation could not be obtained within 1 year. The therapeutic prognosis for sexual maturation could be made based on the response to the hCG test at 6 months of gonadotropin therapy. In conclusion, the maturity of germ cells before treatment, which varies widely among patients with IHH, is a sensitive parameter for hypothalamo-pituitary-testicular function and the efficacy of gonadotropin therapy for testicular function. In severe IHH groups, to obtain satisfactory sexual maturation, the administration of testosterone should be considered in addition to gonadotropin replacement.

Testicular Findings, Endocrine Features and Therapeutic Responses of Men with Idiopathic Hypogonadotropic Hypogonadism