Sensitivity of luteinizing hormone and gonadal steroid responses to single intranasal administration of an LHRH agonist (Hoe-766) in young normal adult men
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While intranasal administration of the potent LHRH agonist [D-Ser (TBL))6, des-Gly-NH2 10] LHRH ethylamide, Hoe-766,at the doses of 50 or 10μg, has little effect on serum LH levels, doses of 200, 500, 1250 or 2500μg cause a rapid and marked stimulation. A near-maximal effect is observed at 30 min with a 4- to 5-fold stimulation of serum LH concentration. A progressive increase of serum testosterone (T) levels is observed on the day of treatment with doses of 200μg and higher of the LHRH agonist with an effect lasting for 24 h at the 2 highest doses used. The increase of serum T levels at the 3 highest doses of Hoe-766 is followed by a decrease of androgen levels during the first throughout the third post treatment days. This temporary decrease of serum T levels is followed by a return to normal diurnal cyclicity and levels at later time intervals. An almost superimposable pattern is observed on serum 170H-progesterone levels: increase of serum levels lasting for up to 24 h followed by loss of diurnal cyclicity and low concentration during the first to third post treatment days. Plasma 17β-estradiol concentrations are increased for 48 h after administration of the two highest doses of Hoe-766 with a return to normal at later time intervals. The present data show that near-maximal stimulation of serum LH levels as well as 170H-progesterone, testosterone and 17β-estradiol secretion can be achieved by doses of Hoe-766 ranging between 200 and 500μg by the intranasal route. Moreover, doses of Hoe-766 leading to a stimulation of LH and androgen secretion cause a transient loss of diurnal cyclicity and low levels of circulating T and 170H-progesterone lasting for one to three days with a complete return to normal at later time intervals. It is thus suggested that intranasal doses of Hoe-766 ranging from 200 to 500μg could be used chronically to inhibit androgen secretion in men for treatment of androgen dependent diseases such as cancer of the prostate and benign prostatic hyperplasia.
Key-wordsLHRH agonist testicular steroids diurnal variation progesterone 17OH-progesterone desensitization
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