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      Toward More Targeted and Cost-Effective Gonadotropin-Releasing Hormone Analog Treatment in Girls with Central Precocious Puberty

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          Abstract

          The use of gonadotropin-releasing hormone analogs (GnRHa) for the treatment of central precocious puberty (CPP), especially in girls, has increased rapidly in recent years. In the context of a secular trend towards earlier puberty onset, many girls now treated for CPP are healthy children experiencing puberty onset within the early end of the normal range. Justifications for GnRHa treatment include the preservation of adult height (AH) potential and the alleviation of presumed distress of early maturation and menarche. With a case of a family requesting treatment for an 8-year-old girl in early puberty as a background, studies of the effect of untreated CPP and of GnRHa treatment of CPP on AH are reviewed. In addition, the limited evidence relating CPP to significant psychological distress – in part due to early menses, and for the amelioration of such distress by GnRHa treatment – is discussed. Taken together, current information suggests that for girls with mildly early onset of puberty (ages 7–9 years), an informed assent discussion with the family should include the consideration of reassurance and observation for many girls who might otherwise receive 2–4 years of GnRHa treatment for a poorly defined benefit and at a cost of at least $20–30,000 per year.

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          Most cited references26

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          Secondary Sexual Characteristics and Menses in Young Girls Seen in Office Practice: A Study from the Pediatric Research in Office Settings Network

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            Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls.

            The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The kappa statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage>or=2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage>or=2. The prime determinant of height velocity was pubertal status. In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.
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              Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity.

              The objective of the study was to determine whether height gain after discontinuation of gonadotropin-suppressive (GnRHa) therapy differs in girls with sexual precocity diagnosed at various ages and assess its influence on final height (FHt) outcome. We compared data on post-GnRHa treatment course and FHt of 115 girls [22 diagnosed before chronological age of 6 yr; 38 between ages 6 and 8 yr; and 55 early fast puberty (EFP) between ages 8 and 9 yr] treated with GnRHa from Tanner stage 2-3 to chronological age 11-12 yr and bone age 12-12.5 yr. Despite comparable bone age at cessation of treatment, similar time to resumption of puberty (0.6 +/- 0.7, 0.5 +/- 0.7, and 0.5 +/- 0.7 yr), and age at menarche (12.6 +/- 0.5, 12.6 +/- 0.6, and 12.7 +/- 0.9 yr), height gain from cessation of therapy to FHt was greater and time to epiphyseal fusion was longer in the younger central precocious puberty (CPP) than in the older CPP (P < 0.05) and EFP (P < 0.001) groups. The percentage of residual growth predicted at discontinuation of treatment was achieved only by the younger CPP (6.6 +/- 1.6% vs. 6.7 +/- 1.6%), whereas in older CPP and EFP, it was significantly lower (6.2 +/- 1.6% vs. 4.6 +/- 2.7% and 6.3 +/- 1.5% vs. 3.6 +/- 1.5%, respectively). FHt of these two groups was compromised, compared with FHt predicted at discontinuation of treatment (P < 0.01 and P < 0.001, respectively). Girls with sexual precocity diagnosed after the age of 6 yr exhibit earlier epiphyseal fusion with diminished posttreatment height gain and compromised FHt. Because recovery of gonadal axis was similar in all girls, differences were probably due to pretreatment intrinsic changes in the growth plate. Prediction of residual growth at discontinuation of treatment is unreliable in these girls.
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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2018
                September 2018
                26 July 2018
                : 90
                : 1
                : 1-7
                Affiliations
                [_a] aDivision of Endocrinology, Children’s National Health System, Washington, District of Columbia, USA
                [_b] bDivision of Endocrinology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
                [_c] cDivision of Pediatric Diabetes and Endocrinology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
                Author notes
                *Paul B. Kaplowitz, MD, Division of Endocrinology, Children’s National Health System, 111 Michigan Ave. NW, Washington, DC 20010 (USA), E-Mail pkaplowi@childrensnational.org
                Article
                491103 Horm Res Paediatr 2018;90:1–7
                10.1159/000491103
                30048994
                77635652-3dd6-47af-830c-a53df84b5d7f
                © 2018 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
                : 24 March 2018
                : 20 June 2018
                Page count
                Pages: 7
                Categories
                Mini Review

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Gonadotropin-releasing hormone analogs,Precocious puberty,Central precocious puberty,Hormone therapy,Cost-effectiveness

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