Estrogen Induction of Luteinizing Hormone Release in Castrated Adult Human Males*

Abstract

Circulating levels of gonadotropins, testosterone, and estradiol (E2) were determined in six castrated adult male subjects. Four subjects were sequentially given 1.5 and 5 mg E₂ benzoate (E₂B) im daily for 9 days in two consecutive experiments performed 4–6 days and 6–8 weeks after orchidectomy. The remaining two patients were treated with 5 mg E₂B for 9 days 3 and 4 weeks, respectively, after orchidectomy. Three of these patients were taking oral estrogens before the study. During treatment each subject demonstrated a dose-dependent suppression of FSH and LH with a subsequent risein LH from nadir to levels well above control values, while E₂ concentrations remained elevated. In patients not on chronic estrogen treatment both doses of estradiol induced a LH surge on the fifth or sixth day which was comparabl in magnitude and duration to the spontaneous peak seen at midcycle in normal women. In three estrogen-pretreated subjects, the 5-mg dose of E₂B induce a LH discharge which consisted of multiple peaks occurring on the second to fourth day of treatment. The studies in men not taking oral estrogens seem to show an activation delay from the initiation of treatment until the onset of the induced LH surge which is longer than those in normal women and estrogen-pretreated men. Multiple blood sampling showed that during positive feedback LH values were elevated in the morning and declined progressively during the day. A positive feedbac effect on the secretion of FSH could not be demonstrated at either dose of estrogen. In all subjects, serum testosterone concentrations were extremely low and levels did not change during treatment. These results demonstrate that in the adult human male, exogenous E₂ when administered in sufficient doses for a prolonged period of time, has a biphasic effect on pituitary LH release. It is concluded that in the human male, exposure of the hypothalamic pituitary unit to androgens throughout fetal and postnatal life does not completely abolish the capacity of the cyclic system to respond to the stimulatory action of estrogen, but th sensitivity of the responsiveness is blunted by the presence of circulating testosterone.