FAILURE OF POSITIVE FEEDBACK IN NORMAL MEN AND SUBJECTS WITH TESTICULAR FEMINIZATION

The abdity of the hypothalamic-pituitary unit to release luteinizing hormone (LH) in response to oestrogen Cpositive feedback) was studied in normal men and women and in subjects with testicular feminization or XY gonadal dysgenesis. Ethinyloestra-diol (200 μg a day for 3 days) given orally to six regularly menstruating women during the early to mid follicular phase of the cycle evoked an LH surge which started between 48 and 72 h after the initiation of treatment. A similar positive feedback effect on the secretion of follicle-stimulating hormone (FSH) could not be demonstrated. In eight normal men there was no evidence for a stimulatory effect of ethinyl-oestradiol (in doses of 200 μg or 500 μg a day for 3 days) on gonadotrophin release even though the levels of plasma ethyloestradiol in men on the higher dosage regime were greater than those found in women. Changes of peripheral LH, but not FSH, in men were inversely related to plasma ethinyloestradiol concentrations. A patient with XY pure gonadal dysgenesis exhibited a female type of LH release in response to ethinyloestradiol administration (200 μg a day for 3 days), but two patients with the syndrome of testicular feminization failed to release LH. The results suggest that normal adults of the two sexes differ in their ability to respond to ethinyloestradiol administration with LH release. The female response in XY gonadal dysgenesis emphasizes the importance of testicular secretions for the suppression of positive feedback whereas the male type of response in cases of testicular feminization indicates that testosterone does not represent the central mediator of this testicular function. The reported observations are compatible with the concept that the organizing action of the testes on positive feedback is mediated through 17β-oestradiol.