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      Antagonistic and Agonistic GnRH Analogue Treatment of Precocious Puberty: Tracking Gonadotropin Concentrations in Urine

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          Abstract

          Background: The pharmacodynamics of gonadotropin-releasing hormone (GnRH) agonists includes an initial ‘flare-up’ of the pituitary-gonadal axis, followed by reduced luteinizing hormone (LH) secretion. The question is if combining a short-acting antagonist with a long-acting agonist can diminish gonadotropin flare-up. Methods: To achieve quick downregulation in patients with recently diagnosed central precocious puberty (CPP, 7 patients) or short stature with short predicted final height (3 patients), we combined the GnRH antagonist cetrorelix (3 subcutaneous injections every 72 h) at the beginning of GnRH agonist treatment (leuprorelin or triptorelin) in 6 patients and compared the effect to 4 patients treated solely with GnRH agonist. To monitor effects, we measured LH and FSH concentrations in urine collected from initial morning urination during the first month of treatment. Results: In both treatment groups, gonadotropin flare-up could be detected in urine levels increased due to the flare-up phenomenon which was of short duration (<5 days) in the majority (5 of 6) of combined-treated patients and in the minority (1 of 4) of patients treated by agonist alone. During the first 10 days of treatment, mean LH concentration measured in urine was significantly lower in 4 CPP patients treated by the combined therapy compared to 3 CPP patients treated by the agonist only (mean LH combined therapy: 10.4 ± 2.8 vs. 20.1 ± 11.0 mU/ml in the agonist-only group, mean ± SEM, p < 0.05). Significant correlations between stimulated serum LH in GnRH test prior to treatment and maximum urine LH after initiating GnRH analogue treatment (r = 0.547, p = 0.043), as well as basal serum LH and basal urine LH (r = 0.685, p = 0.014) were found. Conclusion: Combined GnRH agonist and antagonist treatment led to rapid gonadotropin suppression. Also, urine measurements of LH and FSH seemed suitable for monitoring gonadotropin-inhibiting or -stimulating properties of GnRH analogues in individual patients. However, a controlled trial of a larger patient cohort is required to decide which treatment is the most effective.

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          Most cited references11

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          Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone

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            Pubertal staging in boys.

            To determine the earliest signs of pubertal maturation, we followed 515 boys, aged 10 to 15 years at intake, every 6 months for 3 years. Changes in age, height, weight, body mass index, and serum levels of sex steroid hormones were significantly related to pubertal stage (PS). The earliest clinical stage of pubertal maturation, designated PS2a, was represented by the absence of public hair and a testicular volume 3 cc or greater; 6 months later, further maturation had occurred in 82% of these boys. Inclusion of PS2a as the earliest stage of puberty may help allay concerns about boys with perceived delayed maturation, and may allow more precise definition of early puberty.
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              Management and outcome of central precocious puberty.

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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2005
                July 2005
                19 July 2005
                : 63
                : 5
                : 257-262
                Affiliations
                aDepartment of Pediatrics, University of Bonn, Bonn, and bPraxis für Pädiatrische Endokrinologie, Frankfurt, Germany
                Article
                86685 Horm Res 2005;63:257–262
                10.1159/000086685
                15995342
                547e66df-4c27-43d7-9c44-0ffad3b7a32b
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 29 June 2004
                : 29 March 2005
                Page count
                Figures: 2, Tables: 2, References: 16, Pages: 6
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Antagonist,Gonadotropin flare-up,Precocious puberty,Gonadotropin-releasing hormone,Agonist,Urine gonadotropins

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