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RESEARCH PRODUCT

Gonadotropin Secretion in Eugonadotropic Human Males and Postmenopausal Females Under Long Term Application of a Potent Analog of Gonadotropin-Releasing Hormone

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Long-acting analogs are of special interest in long-term treatment with gonadotropin-releasing hormone (GnRH). However, inhibitory effects of agonist analogs on gonadotropin secretion or on reproductive processes have been observed in rats as well as in human males. Since these inhibitory effects seem to be dose-related, we checked the findings for d-Leu 6 -des-Gly 10 -GnRH-ethylamide within the dose range proposed by us for treatment. In six eugonadotropic human males, a significant decrease of luteinizing hormone and follicle-stimulating hormone responsiveness to a standard dose of GnRH and significant decrease of testosterone basal secretion were observed after 2 and 4weeks of subcutaneous administration of 5μg of d-Leu 6 -des-Gly 10 -GnRH-ethylamide twice daily. In two eugonadotropic males, these effects could not be observed under pernasal administration of 50μg of the substance for 4weeks. In two postmenopausal women, subcutaneous long-term administration of 5μg of the substance produced a marked decrease of basal serum levels and decreased responsiveness of both gonadotropins within 2weeks of application. In one of the women, reversibility of the changes was tested 3months after treatment and could be confirmed. The findings are of great importance for therapeutic trials with d-Leu 6 -des-Gly 10 -GnRH-ethylamide and other GnRH analogs. They show that investigations are still necessary to find the optimal therapeutic regimens for this substance.