{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:35:30Z","timestamp":1780986930487,"version":"3.54.1"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003061","name":"Erasmus MC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neuroendocrine tumors (NETs) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations. An extensive workup was performed for 2 index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Clinically significant ovarian estrogen production was demonstrated by a combination of ovarian vein sampling and normalization of circulating estrogen levels after oophorectomy. Immunohistochemical analyses revealed marked aromatase immunoactivity in the ovarian NET cells, while CYP17A1 and SF-1 were detected in the adjacent ovarian stromal cells but not the NET cells. Ex vivo and in vivo endocrine tests were unable to identify a paracrine mechanism of ovarian estradiol overproduction by NET cells. A retrospective search of electronic medical records revealed that 21% (14\/66) of postmenopausal patients with an ovarian NET localization reported symptoms of vaginal blood loss. Together, these findings support the presence of a novel NET-associated hormonal syndrome.<\/jats:p>","DOI":"10.1093\/ejendo\/lvae075","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T17:17:17Z","timestamp":1719335837000},"page":"K1-K4","source":"Crossref","is-referenced-by-count":3,"title":["Ovarian neuroendocrine tumor metastases can induce estrogen production in postmenopausal patients"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-5925","authenticated-orcid":false,"given":"Merijn C F","family":"Mulders","sequence":"first","affiliation":[{"name":"ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute , 3015 GD Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Lousie F","family":"van Velthuysen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus Medical Centre , 3015 GD Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Maria","family":"Roes","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Erasmus Medical Centre Cancer Institute , 3015 GD Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo J","family":"Hofland","sequence":"additional","affiliation":[{"name":"ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute , 3015 GD Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6600-8641","authenticated-orcid":false,"given":"Hironobu","family":"Sasano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tohoku University Graduate School of Medicine , Sendai, Miyagi 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter W","family":"de Herder","sequence":"additional","affiliation":[{"name":"ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute , 3015 GD Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0679-6209","authenticated-orcid":false,"given":"Johannes","family":"Hofland","sequence":"additional","affiliation":[{"name":"ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute , 3015 GD Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"issue":"2","key":"2024073119302286600_lvae075-B1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1210\/endrev\/bnz004","article-title":"Advances in the diagnosis and management of well-differentiated neuroendocrine neoplasms","volume":"41","author":"Hofland","year":"2020","journal-title":"Endocr Rev"},{"issue":"3","key":"2024073119302286600_lvae075-B2","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1210\/endrev\/bnad035","article-title":"What is carcinoid syndrome? 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