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      Effects of Growth Hormone Replacement Therapy on IGF-Related Parameters and on the Pituitary-Gonadal Axis in GH-Deficient Males

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          Abstract

          It has been suggested that growth hormone (GH) may play a regulatory role in male reproductive function. To express full anabolic effect in immature boys testosterone apparently requires the presence of GH. In GH-deficient adults, GH replacement therapy exerts a variety of anabolic actions, some of which are similar to the effects of gonadal steroids. However, little is known about the potential effects of GH on gonadal steroids and on dynamic tests of pituitary-gonadal function in adults with GH deficiency. We evaluated the pituitary-gonadal axis in a 4-month double-blind, placebo-controlled GH study in 13 young males with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH treatment significantly increased serum levels of total IGF-I from 98 (68) to 323 (126) µg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) µg/l, IGFBP-3 from 1,874 (1,178) to 3,520 (778) µg/l and ALS levels from 9,182 (5,524) to 16,872 (6,278) µg/l (all p < 0.0001). We found no differences in basal testosterone levels in the 13 patients between the GH and placebo treatment periods (21.9 (5.1) vs. 24.5 (8.1) nmol/l, nonsignificant). Furthermore, no effect of GH on the testicular response to hCG after 72 h was seen compared to placebo (36.2 (6.4) vs. 38.8 (10.3) nmol/l). In addition, no differences existed in basal SHBG, DHT, free testosterone, Δ4-adion and DHEA-S levels. There were no statistically significant differences in maximal FSH and LH response to a GnRH challenge between the GH and the placebo periods (15.7 (5.3) vs. 18.0 (8.8) U/l and 47.0 (26.4) vs. 40.4 (26.5) U/l, respectively). Furthermore, there was no effect on cortisol responses after ACTH between the GH and the placebo periods. However, significantly higher estradiol levels were seen after GH treatment (110 (50) pmol/l) compared to after placebo (89 (34) pmol/l, p = 0.03). Prostate-specific antigen levels decreased after GH treatment compared to after placebo (0.42 (0.54) vs. 0.47 (0.48) µg/l) and this difference almost reached statistical significance (p = 0.059). Inhibin-B levels were significantly lower in hypogonadal patients substituted with androgens, but GH had no effect on inhibin-B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult males resulted in significant increases in total and free IGF-I as well as in ALS levels in all patients, but had no significant effect on: (1) the pituitary FSH and LH response to GnRH; (2) basal and hCG-stimulated levels of androgens and SHBG; (3) basal inhibin-B levels; (4) ACTH-stimulated cortisol secretion. By contrast, GH administration had subtle anti-androgenic effects in terms of elevated elevated estradiol levels and decreased prostate-specific antigen levels, although both parameters remained within the normal range. Thus, at the level of blood chemistry the effects of GH administration do not appear to involve major alterations in the pituitary-gonadal axis.

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          Most cited references9

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          Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index

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            Testosterone Replacement Increases Fat-Free Mass and Muscle Size in Hypogonadal Men

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              Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction

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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
                1998
                June 1998
                15 May 1998
                : 49
                : 6
                : 269-278
                Affiliations
                a Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, and b Department of Internal Medicine (Endocrinology and Diabetes), Århus Kommunehospital, Århus, Denmark; c School of Biological and Molecular Sciences, Oxford Brookes University, Oxford, UK
                Article
                23186 Horm Res 1998;49:269–278
                10.1159/000023186
                9623518
                805f6226-5b6c-43ab-bb25-2c845bd3ef12
                © 1998 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
                Page count
                Figures: 3, Tables: 4, References: 51, Pages: 10
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                hCG test,GH-deficient adults,Androgens,Semen quality,Prostate-specific antigen,Inhibin B,GH replacement therapy,Sex hormone-binding globulin,GnRH test

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