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Successful Pregnancy after Improving Insulin Resistance with the Glucagon-Like Peptide-1 Analogue in a Woman with Polycystic Ovary Syndrome: A Case Report and Review of the Literature

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Gynecologic and Obstetric Investigation

S. Karger AG

27300746

10.1159/000446951

Polycystic ovary syndrome, Insulin resistance, Infertility, Exenatide, Metformin

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Abstract

The polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. It is diagnosed by the presence of hyperandrogenemia, insulin resistance (IR), obesity and other endocrine or metabolic disorders. Exenatide (EX) is a kind of glucagon-like peptide, which is a new option for patients with diabetes mellitus. We present a patient with infertility for PCOS. She was overweight and her medical history included IR, right-sided ovarian mucinous cystadenomas, and left-sided teratoma. Although she had been treated with ovarian surgery, clomiphene citrate and gonadotropins, weight loss and metformin, which have been effective for dominant follicle development, she still failed to conceive. Then EX was initiated to intervene for 2 months. EX treatment was successful to improve IR; after that the infertile woman with PCOS became pregnant. EX improves IR and reproduction capacity in PCOS patients, reducing insulin level and ameliorating endocrine disorders, thereby improving ovarian function, promoting follicle development, and providing new avenues for the treatment of infertility with PCOS.

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Most cited references 13

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Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline.

The aim was to formulate practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS). An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer developed the guideline. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries). Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women. Hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women. Evaluation of women with PCOS should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease. Hormonal contraceptives are the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. Clomiphene is currently the first-line therapy for infertility; metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irregularities, but it has limited or no benefit in treating hirsutism, acne, or infertility. Hormonal contraceptives and metformin are the treatment options in adolescents with PCOS. The role of weight loss in improving PCOS status per se is uncertain, but lifestyle intervention is beneficial in overweight/obese patients for other health benefits. Thiazolidinediones have an unfavorable risk-benefit ratio overall, and statins require further study.
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The impact of obesity on reproduction in women with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.
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Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system.

To determine whether insulin stimulates human ovarian testosterone production in the polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system, thecal cells from polycystic ovary syndrome women were isolated and cultured. Insulin and insulin-like growth factor I stimulated thecal testosterone biosynthesis. Antibody blockade of the insulin receptor abolished insulin's stimulatory action, whereas effective antibody blockade of the insulin-like growth factor I receptor did not alter insulin's stimulation of thecal testosterone biosynthesis. A chiro-inositol containing glycan (INS-2) increased thecal testosterone biosynthesis. Preincubation of cells with an antiinositolglycan antibody (A23939 or alpha IGP) abolished insulin's stimulatory effect, but not that of hCG. These findings suggest that inositolglycans serve as the signal transduction system for insulin's stimulation of human thecal testosterone biosynthesis.

Author and article information

Affiliations
Research Institute of Obstetrics and Gynaecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Journal
GOI
Gynecol Obstet Invest
10.1159/issn.0378-7346
Gynecologic and Obstetric Investigation
Gynecol Obstet Invest
S. Karger AG (Basel, Switzerland karger@123456karger.com http://www.karger.com )
0378-7346
1423-002X
September 2016
15 June 2016
: 81
: 5
: 477-480
© 2016 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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. 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.

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Figures: 1, References: 16, Pages: 4
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