Acute Effects of Testosterone Infusion on the Serum Luteinizing Hormone Profile in Eumenorrheic and Polycystic Ovary Syndrome Adolescents

Context: Little is known about the neuroendocrine effects of androgens on the GnRH-LH unit in females. Objective: Our objective was to evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and polycystic ovary syndrome (PCOS) adolescents. Design and Setting: We conducted a prospect...

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Veröffentlicht in:The journal of clinical endocrinology and metabolism 2009-09, Vol.94 (9), p.3602-3610
Hauptverfasser: Ropelato, María Gabriela, García Rudaz, María Cecilia, Escobar, María Eugenia, Bengolea, Sonia Viviana, Calcagno, María Luján, Veldhuis, Johannes D., Barontini, Marta
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container_end_page 3610
container_issue 9
container_start_page 3602
container_title The journal of clinical endocrinology and metabolism
container_volume 94
creator Ropelato, María Gabriela
García Rudaz, María Cecilia
Escobar, María Eugenia
Bengolea, Sonia Viviana
Calcagno, María Luján
Veldhuis, Johannes D.
Barontini, Marta
description Context: Little is known about the neuroendocrine effects of androgens on the GnRH-LH unit in females. Objective: Our objective was to evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and polycystic ovary syndrome (PCOS) adolescents. Design and Setting: We conducted a prospective, longitudinal, randomized, double-blind study at a pediatric endocrinology clinical research center. Participants: Seven nonobese PCOS adolescents and seven matched controls (C) were studied in the early follicular phase of three consecutive menstrual cycles or in three consecutive months. Intervention: Pulsatile LH release was determined during saline [baseline (B)] and constant testosterone (T) infusions: low dose (T-LD) 0.75 and high dose (T-HD) 2.5 mg/12 h iv. Blood samples were drawn every 20 min overnight. Main Outcome Measures: LH (immunofluorometric assay) and T (electrochemiluminescence immunoassay) were determined at B, and during both T-LD and T-HD. LH profiles were analyzed by deconvolution and approximate entropy analyses. Results: On T-LD, C and PCOS serum T levels increased 2- to 3-fold vs. B. On T-HD, T values doubled in both groups vs. T-LD. Controls on T-LD had greater 12-h pulsatile LH secretion rate (P < 0.05 vs. B) and on T-HD had lower mean, pulsatile, basal LH release and LH approximate entropy (vs. B, P < 0.05). PCOS did not respond to T-LD. High-dose T did not alter mean LH in PCOS but increased pulsatile and reduced basal LH secretion. Conclusions: PCOS adolescents have impaired suppression of pulsatile LH secretion rate consistent with reduced androgen negative feedback. Attenuation of T feedback in nonobese adolescents with PCOS extends the pathophysiology of this syndrome. PCOS adolescents have impaired suppression of pulsatile luteinizing hormone secretion under high dose of testosterone infused overnight, which is consistent with reduced pituitary sensitivity to androgen. negative feedback.
doi_str_mv 10.1210/jc.2009-0402
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Objective: Our objective was to evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and polycystic ovary syndrome (PCOS) adolescents. Design and Setting: We conducted a prospective, longitudinal, randomized, double-blind study at a pediatric endocrinology clinical research center. Participants: Seven nonobese PCOS adolescents and seven matched controls (C) were studied in the early follicular phase of three consecutive menstrual cycles or in three consecutive months. Intervention: Pulsatile LH release was determined during saline [baseline (B)] and constant testosterone (T) infusions: low dose (T-LD) 0.75 and high dose (T-HD) 2.5 mg/12 h iv. Blood samples were drawn every 20 min overnight. Main Outcome Measures: LH (immunofluorometric assay) and T (electrochemiluminescence immunoassay) were determined at B, and during both T-LD and T-HD. LH profiles were analyzed by deconvolution and approximate entropy analyses. Results: On T-LD, C and PCOS serum T levels increased 2- to 3-fold vs. B. On T-HD, T values doubled in both groups vs. T-LD. Controls on T-LD had greater 12-h pulsatile LH secretion rate (P &lt; 0.05 vs. B) and on T-HD had lower mean, pulsatile, basal LH release and LH approximate entropy (vs. B, P &lt; 0.05). PCOS did not respond to T-LD. High-dose T did not alter mean LH in PCOS but increased pulsatile and reduced basal LH secretion. Conclusions: PCOS adolescents have impaired suppression of pulsatile LH secretion rate consistent with reduced androgen negative feedback. Attenuation of T feedback in nonobese adolescents with PCOS extends the pathophysiology of this syndrome. PCOS adolescents have impaired suppression of pulsatile luteinizing hormone secretion under high dose of testosterone infused overnight, which is consistent with reduced pituitary sensitivity to androgen. negative feedback.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2009-0402</identifier><identifier>PMID: 19567528</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adolescent ; Biological and medical sciences ; Double-Blind Method ; Endocrinopathies ; Feedback, Physiological ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Longitudinal Studies ; Luteinizing Hormone - blood ; Luteinizing Hormone - secretion ; Medical sciences ; Polycystic Ovary Syndrome - metabolism ; Prospective Studies ; Testosterone - blood ; Testosterone - pharmacology ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2009-09, Vol.94 (9), p.3602-3610</ispartof><rights>Copyright © 2009 by The Endocrine Society</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5126-b29879c330f9e752f3e2db798dada8701dfe58cc3ce0f2f31d5435269c0a3d033</citedby><cites>FETCH-LOGICAL-c5126-b29879c330f9e752f3e2db798dada8701dfe58cc3ce0f2f31d5435269c0a3d033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21923636$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19567528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ropelato, María Gabriela</creatorcontrib><creatorcontrib>García Rudaz, María Cecilia</creatorcontrib><creatorcontrib>Escobar, María Eugenia</creatorcontrib><creatorcontrib>Bengolea, Sonia Viviana</creatorcontrib><creatorcontrib>Calcagno, María Luján</creatorcontrib><creatorcontrib>Veldhuis, Johannes D.</creatorcontrib><creatorcontrib>Barontini, Marta</creatorcontrib><title>Acute Effects of Testosterone Infusion on the Serum Luteinizing Hormone Profile in Eumenorrheic and Polycystic Ovary Syndrome Adolescents</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context: Little is known about the neuroendocrine effects of androgens on the GnRH-LH unit in females. Objective: Our objective was to evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and polycystic ovary syndrome (PCOS) adolescents. Design and Setting: We conducted a prospective, longitudinal, randomized, double-blind study at a pediatric endocrinology clinical research center. Participants: Seven nonobese PCOS adolescents and seven matched controls (C) were studied in the early follicular phase of three consecutive menstrual cycles or in three consecutive months. Intervention: Pulsatile LH release was determined during saline [baseline (B)] and constant testosterone (T) infusions: low dose (T-LD) 0.75 and high dose (T-HD) 2.5 mg/12 h iv. Blood samples were drawn every 20 min overnight. Main Outcome Measures: LH (immunofluorometric assay) and T (electrochemiluminescence immunoassay) were determined at B, and during both T-LD and T-HD. LH profiles were analyzed by deconvolution and approximate entropy analyses. Results: On T-LD, C and PCOS serum T levels increased 2- to 3-fold vs. B. On T-HD, T values doubled in both groups vs. T-LD. Controls on T-LD had greater 12-h pulsatile LH secretion rate (P &lt; 0.05 vs. B) and on T-HD had lower mean, pulsatile, basal LH release and LH approximate entropy (vs. B, P &lt; 0.05). PCOS did not respond to T-LD. High-dose T did not alter mean LH in PCOS but increased pulsatile and reduced basal LH secretion. Conclusions: PCOS adolescents have impaired suppression of pulsatile LH secretion rate consistent with reduced androgen negative feedback. Attenuation of T feedback in nonobese adolescents with PCOS extends the pathophysiology of this syndrome. PCOS adolescents have impaired suppression of pulsatile luteinizing hormone secretion under high dose of testosterone infused overnight, which is consistent with reduced pituitary sensitivity to androgen. negative feedback.</description><subject>Adolescent</subject><subject>Biological and medical sciences</subject><subject>Double-Blind Method</subject><subject>Endocrinopathies</subject><subject>Feedback, Physiological</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Luteinizing Hormone - blood</subject><subject>Luteinizing Hormone - secretion</subject><subject>Medical sciences</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Prospective Studies</subject><subject>Testosterone - blood</subject><subject>Testosterone - pharmacology</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkU2PUyEUhonROLW6c23Y6Mo78nG_WDaT6kzSZCaZMXFHKBwslQsV7p1J_Qf-a7lpoxs5EEJ43sM5Lwi9peSSMko-7fUlI0RUpCbsGVpQUTdVR0X3HC0IYbQSHft2gV7lvCeE1nXDX6ILKpq2a1i_QL9XehoBr60FPWYcLX6APMY8QooB8E2wU3Yx4DLHHeB7SNOAN0Xigvvlwnd8HdMwk3cpWucBu4DX0wAhprQDp7EKBt9Ff9THPJbj7aNKR3x_DCbFAfDKRA9ZQxjza_TCKp_hzXlfoq-f1w9X19Xm9svN1WpT6Yayttoy0XdCc06sgNKD5cDMthO9UUb1HaHGQtNrzTUQW26paWresFZoorghnC_Rh1PeQ4o_p9KsHFypwHsVIE5Ztl3L-7qmBfx4AnWKOSew8pDcUMqXlMjZernXcrZeztYX_N0577QdwPyDz14X4P0ZUFkrb5MK2uW_HKOC8bbEEtUn7in68g35h5-eIMkdKD_uJCmjbru-ml8uQUhVVjvL-EkGwUSdXIBDgpzlPk4pFEP_X_UfGhavAQ</recordid><startdate>200909</startdate><enddate>200909</enddate><creator>Ropelato, María Gabriela</creator><creator>García Rudaz, María Cecilia</creator><creator>Escobar, María Eugenia</creator><creator>Bengolea, Sonia Viviana</creator><creator>Calcagno, María Luján</creator><creator>Veldhuis, Johannes D.</creator><creator>Barontini, Marta</creator><general>Endocrine Society</general><general>Copyright by The Endocrine Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200909</creationdate><title>Acute Effects of Testosterone Infusion on the Serum Luteinizing Hormone Profile in Eumenorrheic and Polycystic Ovary Syndrome Adolescents</title><author>Ropelato, María Gabriela ; García Rudaz, María Cecilia ; Escobar, María Eugenia ; Bengolea, Sonia Viviana ; Calcagno, María Luján ; Veldhuis, Johannes D. ; Barontini, Marta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5126-b29879c330f9e752f3e2db798dada8701dfe58cc3ce0f2f31d5435269c0a3d033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Biological and medical sciences</topic><topic>Double-Blind Method</topic><topic>Endocrinopathies</topic><topic>Feedback, Physiological</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Luteinizing Hormone - blood</topic><topic>Luteinizing Hormone - secretion</topic><topic>Medical sciences</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Prospective Studies</topic><topic>Testosterone - blood</topic><topic>Testosterone - pharmacology</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ropelato, María Gabriela</creatorcontrib><creatorcontrib>García Rudaz, María Cecilia</creatorcontrib><creatorcontrib>Escobar, María Eugenia</creatorcontrib><creatorcontrib>Bengolea, Sonia Viviana</creatorcontrib><creatorcontrib>Calcagno, María Luján</creatorcontrib><creatorcontrib>Veldhuis, Johannes D.</creatorcontrib><creatorcontrib>Barontini, Marta</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ropelato, María Gabriela</au><au>García Rudaz, María Cecilia</au><au>Escobar, María Eugenia</au><au>Bengolea, Sonia Viviana</au><au>Calcagno, María Luján</au><au>Veldhuis, Johannes D.</au><au>Barontini, Marta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute Effects of Testosterone Infusion on the Serum Luteinizing Hormone Profile in Eumenorrheic and Polycystic Ovary Syndrome Adolescents</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2009-09</date><risdate>2009</risdate><volume>94</volume><issue>9</issue><spage>3602</spage><epage>3610</epage><pages>3602-3610</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context: Little is known about the neuroendocrine effects of androgens on the GnRH-LH unit in females. Objective: Our objective was to evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and polycystic ovary syndrome (PCOS) adolescents. Design and Setting: We conducted a prospective, longitudinal, randomized, double-blind study at a pediatric endocrinology clinical research center. Participants: Seven nonobese PCOS adolescents and seven matched controls (C) were studied in the early follicular phase of three consecutive menstrual cycles or in three consecutive months. Intervention: Pulsatile LH release was determined during saline [baseline (B)] and constant testosterone (T) infusions: low dose (T-LD) 0.75 and high dose (T-HD) 2.5 mg/12 h iv. Blood samples were drawn every 20 min overnight. Main Outcome Measures: LH (immunofluorometric assay) and T (electrochemiluminescence immunoassay) were determined at B, and during both T-LD and T-HD. LH profiles were analyzed by deconvolution and approximate entropy analyses. Results: On T-LD, C and PCOS serum T levels increased 2- to 3-fold vs. B. On T-HD, T values doubled in both groups vs. T-LD. Controls on T-LD had greater 12-h pulsatile LH secretion rate (P &lt; 0.05 vs. B) and on T-HD had lower mean, pulsatile, basal LH release and LH approximate entropy (vs. B, P &lt; 0.05). PCOS did not respond to T-LD. High-dose T did not alter mean LH in PCOS but increased pulsatile and reduced basal LH secretion. Conclusions: PCOS adolescents have impaired suppression of pulsatile LH secretion rate consistent with reduced androgen negative feedback. Attenuation of T feedback in nonobese adolescents with PCOS extends the pathophysiology of this syndrome. PCOS adolescents have impaired suppression of pulsatile luteinizing hormone secretion under high dose of testosterone infused overnight, which is consistent with reduced pituitary sensitivity to androgen. negative feedback.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>19567528</pmid><doi>10.1210/jc.2009-0402</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Adolescent
Biological and medical sciences
Double-Blind Method
Endocrinopathies
Feedback, Physiological
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
Humans
Longitudinal Studies
Luteinizing Hormone - blood
Luteinizing Hormone - secretion
Medical sciences
Polycystic Ovary Syndrome - metabolism
Prospective Studies
Testosterone - blood
Testosterone - pharmacology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
title Acute Effects of Testosterone Infusion on the Serum Luteinizing Hormone Profile in Eumenorrheic and Polycystic Ovary Syndrome Adolescents
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