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  • Title: Sensitivity of luteinizing hormone and gonadal steroid responses to single intranasal administration of an LHRH agonist (Hoe-766) in young normal adult men.
    Author: Faure N, Labrie F, Belanger A, Lemay A, Raynaud JP, Von der Ohe M, Fazekas AT.
    Journal: J Endocrinol Invest; 1982; 5(6):355-60. PubMed ID: 6820372.
    Abstract:
    While intranasal administration of the potent LHRH agonist [D-Ser (TBU)6, des-Gly-NH210] LHRH ethylamide, Hoe-766, at the doses of 50 or 100 mcg, has little effect on serum luteinizing hormone (LH) levels, doses of 200, 500, 1250, or 2500 mcg cause a rapid and marked stimulation. A near-maximal effect is seen at 30 minutes with a 4- to 5-fold stimulation of serum LH concentration. A progressive increase in serum testosterone (T) levels is observed on the day of treatment with doses of 200 mcg and higher of the LHRH agonist with an effect lasting for 24 hours at the 2 highest doses used. The increase in serum T levels at the 3 highest doses of Hoe-766 is followed by a decrease of androgen levels during the 1st-3rd posttreatment 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 hours followed by loss of diurnal cyclicity and low concentration during the 1st-3rd posttreatment days. Plasma 17beta-estradiol concentrations are increased for 48 hours after administration of the 2 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, 17beta-estradiol secretion can be achieved by doses of Hoe-766 ranging between 200-500 mcg 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 1-3 days with a complete return to normal at a later time. It is suggested that intranasal doses of Hoe-766 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.
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