Sex Steroid Modulation of Gonadotropins in Normal Men and in Androgen Insensitivity Syndrome*

The respective roles of androgens and estrogens in the modulation of LH and FSH secretion in men have not been clearly defined. In this study, we compared gonadotropins basally and after stimulation with gonadotropin-releasing hormone in four states characterized by different sensitivity to sex steroids: 1) in five normal men (intact sensitivity to both androgens and estrogens), 2) in two patients with complete androgen insensitivity syndrome (AIS; selective androgen insensitivity), 3) in normal men treated with clomiphene citrate (selective estrogen insensitivity), and 4) in AIS patients treated with clomiphene (combined androgen and estrogen insensitivity). Basal LH levels were increased in selective androgen and selective estrogen insensitivities; LH levels were elevated further in combined androgen and estrogen insensitivities. The elevated LH levels in AIS were suppressible by exogenous administration of estradiol benzoate. Basal FSH was not increased in selective androgen insensitivity, but was mildly elevated to about the same levels in selective estrogen or in combined androgen and estrogen insensitivities. Insensitivity to sex steroids did not consistently modify the, response of gonadotropins to gonadotropin-releasing hormone in these studies. Testicular modulation of basal LH secretion is exerted importantly by independent direct effects of androgens and estrogens; basal FSH feedback is only partially modulated by estrogens, and modulation of FSH by androgens was not detectable in this study. (J Clin Endocrinol Metab48: 235, 1979)