{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T17:31:53Z","timestamp":1787938313283,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Polycystic ovary syndrome (PCOS) has a prevalence of 8%\u201013%. Given the prevalence, diverse health impacts and variation in care, rigorous evidence\u2010based guidelines are needed in PCOS management. This systematic review with meta\u2010analyses aimed to investigate the effect of the combined oral contraceptive pill (COCP) and\/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials which investigated the effect of COCPs and\/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal was completed. Meta\u2010analyses were conducted, where appropriate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low\u2010quality evidence in adolescents, meta\u2010analyses demonstrated that metformin was better than COCP for BMI (mean difference [MD] \u22124.02 [\u22125.23,\u00a0\u22122.81],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001); COCP was better than metformin for menstrual regulation (MD \u22120.19 [\u22120.25,\u00a0\u22120.13],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.00001). In low\u2010quality evidence in adults, meta\u2010analyses demonstrated that metformin was better than placebo for BMI (MD \u22120.48 [\u22120.94,\u00a0\u22120.02],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03). Combined oral contraceptive pill alone was better than the combination with an anti\u2010androgen for BMI (MD \u22123.04 [\u22125.45,\u00a0\u22120.64],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were subgrouped by BMI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti\u2010androgen to COCP therapy.<\/jats:p>\n                    <jats:p>\n                      Metformin alone has benefits for adult women for management of weight, hormonal and metabolic outcomes, especially for women with BMI\u00a0\u2265\u00a025\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . There is inadequate evidence to suggest the optimal COCP formulation, or dosing regimen and formulation of metformin.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.14013","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T12:47:45Z","timestamp":1557838065000},"page":"479-489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Effect of the combined oral contraceptive pill and\/or metformin in the management of polycystic ovary syndrome: A systematic review with meta\u2010analyses"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-577X","authenticated-orcid":false,"given":"Helena","family":"Teede","sequence":"first","affiliation":[{"name":"Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine Monash University Clayton Victoria Australia"},{"name":"Department of Diabetes and Vascular Medicine Monash Health Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3097-6621","authenticated-orcid":false,"given":"Eliza C.","family":"Tassone","sequence":"additional","affiliation":[{"name":"Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terhi","family":"Piltonen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Rainbow Hospital &amp; Malhotra Nursing and Maternity Home Agra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben W.","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Discipline of Paediatrics, Endocrinology and Diabetes Department, Women's and Children's Hospital The University of Adelaide and Robinson Research Institute North Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma F.","family":"Witchel","sequence":"additional","affiliation":[{"name":"Peadiatric Endocrinology, UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Joham","sequence":"additional","affiliation":[{"name":"Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine Monash University Clayton Victoria Australia"},{"name":"Department of Diabetes and Vascular Medicine Monash Health Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veryan","family":"McAllister","sequence":"additional","affiliation":[{"name":"Polycystic Ovary Association of Australia Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5236-2586","authenticated-orcid":false,"given":"Daniela","family":"Romualdi","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala","family":"Thondan","sequence":"additional","affiliation":[{"name":"Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine Monash University Clayton Victoria Australia"},{"name":"HARP Family Medical Kew Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Costello","sequence":"additional","affiliation":[{"name":"University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L.","family":"Misso","sequence":"additional","affiliation":[{"name":"Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew218"},{"issue":"2","key":"e_1_2_10_3_1","first-page":"604","article-title":"Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome","volume":"102","author":"Gibson\u2010Helm M","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh098"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.5694\/mja11.10915"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2350"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.217"},{"key":"e_1_2_10_8_1","volume-title":"International Evidence\u2010based Guidelines for the Assessment and Management of Polycystic Ovary Syndrome","year":"2018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.05.004"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey256"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13795"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv063"},{"key":"e_1_2_10_13_1","first-page":"CD003053","article-title":"Insulin\u2010sensitising drugs (metformin, rosiglitazone, pioglitazone, D\u2010chiro\u2010inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility","volume":"5","author":"Tang T","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2013.03.007"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1667312"},{"issue":"7","key":"e_1_2_10_16_1","first-page":"e1000097","article-title":"Preferred reporting items for systematic reviews and meta\u2010analyses: the PRISMA statement","volume":"6","author":"Moher D","year":"2009","journal-title":"BMJ"},{"key":"e_1_2_10_17_1","volume-title":"NHMRC Additional Levels of Evidence and Grades for Recommendations for Developers of Guidelines","author":"National Health and Medical Research Council","year":"2009"},{"key":"e_1_2_10_18_1","volume-title":"Manual for ESHRE Guideline Development","author":"Vermeulen N","year":"2014"},{"key":"e_1_2_10_19_1","unstructured":"GRADE Working Group.Grading of Recommendations Assessment Development and Evaluation (GRADE) Guidelines.http:\/\/www.gradeworkinggroup.org\/. 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