Danazol suppression of gonadal estradiol-17 beta secretion--report of two sibling cases with a complete form of testicular feminization on gonadal ultrastructure and endocrine status.

It has been established that the pathogenesis of a complete form of testicular feminization syndrome (TFM) is due to end-organ unresponsiveness to androgens. In the present study, two sibling cases with TFM have been reported with special reference to the effect of danazol (a derivative of 17 alpha-ethynyltestosterone) on gonadal estradiol-17 beta (E2) secretion in vivo and in vitro. Both patients showed hypergonadotropic-hypergonadism with good response to LH-RH. In one case, peripheral blood E2 levels seemed to fall independently of gonadotropins during danazol administration in vivo. Administrations of danazol to the culture media also inhibited E2 secretion from the cultured monolayered cells of the testes. These results suggest a direct inhibitory effect of danazol on gonadal E2 secretion. However, the feedback mechanisms of hypothalamic-pituitary units to E2 were preserved in both cases. Spermatogeneses were almost undetectable as in immature embryonal testes when using either light or electron microscopies, though spermatogonia were differentiated from Sertoli cells by these techniques. Finally, plasma T and E2 levels in both patients were considerably lower after gonadectomy.