Daily administration of 5microgram of D-Ser(TBU)6-LH-RH-EA10 for one week produced a significant increase in the LH response to GnRH in hypogonadotropic hypogonadal subjects and a significant decrease in the response of normal male adults. Basal plasma testosterone concentrations fell in normal controls but were unchanged in the hypogonadal group.
PIP: Daily administration of 5 mcg of the gonadotropin-releasing hormone (GnRH) analogue D-Ser (TBU) 6-LH-RH-EA 10 for 1 week produced a significant increase in the luteinizing hormone (LH) response to GnRH in hypogonadotrophic hypogonadal subjects and a significant decrease in the response of normal male adults. Subjects included 4 men and 2 women with an isolated gonadotropin deficiency and 4 men and 1 woman with hypogonadism secondary to proven craniopharyngioma; 5 adult men of proven fertility served as controls. All sex steroid treatment was discontinued at least 3 months before the study. Basal plasma testosterone concentrations fell in controls but were unchanged in the hypogonadal group 9 days after onset of treatment with the analogue. This difference in responsiveness to LH between normal and hypogonadotrophic hypogonadal subjects has also been recorded following prolonged therapy with natural GnRH. Moreover, this finding implies that the results of Hoe 766 studies in normal subjects cannot be extrapolated. Patients with isolated gonadotropin deficiency showed greater increments in LH secretion than those with craniopharyngiomas. The 3 patients who had not received prior gonadal steroid therapy responded relatively poorly in terms of LH increment, perhaps indicating that the administration of gonadal steroids is associated with increased LH responsiveness and an adult pattern of gonadotropin secretion. The tendency for plasma testosterone levels to rise in the hypogonadotrophic hypogonadal subjects in this study suggests that long-acting GnRH analogues have potential for use in this area.