{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:24:38Z","timestamp":1792185878310,"version":"4.4.0"},"reference-count":16,"publisher":"The Endocrine Society","issue":"7","funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50HD071836"],"award-info":[{"award-number":["P50HD071836"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Santa Monica Bay Woman's Club"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Ovarian hyperandrogenism from polycystic ovary syndrome (PCOS) and hyperinsulinemia from insulin resistance are modulators of ovarian follicle development. We report on a woman with PCOS and hyperandrogenism and severe insulin resistance from metabolic syndrome who received long-term GnRH analogue therapy preceding bilateral salpingo-oophorectomy for massive ovarian enlargement. Ovarian histological examination showed proliferating granulosa cells within antral follicles coexistent with serous cystadenofibromas, demonstrating a unique link between hyperinsulinemia and granulosa cell mitogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Description<\/jats:title>\n                  <jats:p>A 30-year-old woman with PCOS with hyperandrogenism, severe insulin resistance from metabolic syndrome, and nonalcoholic steatohepatitis experienced abdominal pain from bilaterally enlarged ovaries. She had previously experienced a pulmonary embolism while taking oral contraceptives and hepatotoxicity from metformin and spironolactone therapies. Long-term GnRH analogue therapy to induce pituitary desensitization to GnRH successfully decreased gonadotropin-dependent steroidogenesis without improving insulin resistance. Despite GnRH analogue therapy, progressive ovarian enlargement in the presence of hyperinsulinemia from worsening metabolic function eventually required bilateral salpingo-oophorectomy for removal of massively enlarged ovaries. Histological examination showed both ovaries contained proliferating granulosa cells within antral follicles coexistent with serous cystadenofibromas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In women with PCOS and hyperinsulinemia from severe insulin resistance due to metabolic syndrome, granulosa cell proliferation within antral follicles can occur despite long-term GnRH analogue therapy, implicating hyperinsulinemia as a granulosa cell mitogen in the absence of gonadotropin-dependent ovarian function.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2018-02464","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T14:21:21Z","timestamp":1549981281000},"page":"2796-2800","source":"Crossref","is-referenced-by-count":8,"title":["Massive Ovarian Growth in a Woman With Severe Insulin-Resistant Polycystic Ovary Syndrome Receiving GnRH Analogue"],"prefix":"10.1210","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4022-6747","authenticated-orcid":false,"given":"Prapti","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0109-8380","authenticated-orcid":false,"given":"Ariela","family":"Agress","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1319-0598","authenticated-orcid":false,"given":"Vanessa Kasarah","family":"Madrigal","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Magyar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Ostrzega","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio Daniel","family":"Chazenbalk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-1277","authenticated-orcid":false,"given":"Daniel Anthony","family":"Dumesic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"issue":"5","key":"2019123104274416900_B1","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.fertnstert.2004.11.070","article-title":"Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment","volume":"83","author":"DeUgarte","year":"2005","journal-title":"Fertil 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