{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:18:46Z","timestamp":1785777526325,"version":"3.56.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["314061271 \u2013 TRR 205"],"award-info":[{"award-number":["314061271 \u2013 TRR 205"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL\/GEP-NET primary culture cell viability (n = 38\/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In PPGLs, estradiol and progesterone (1\u2005\u00b5m) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ER\u03b1) positivity was detected in 11\/36 PPGLs, including 4\/4 head-and-neck paragangliomas (HNPGLs). ER\u03b1\u2013positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1\u2005\u00b5m) displayed no effects, but higher doses of testosterone (10\u2005\u00b5m) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences\u2014tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL\/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient\u2019s sex and the individual tumor\u2019s genetic\/molecular background. All HNPGLs showed ER\u03b1 positivity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae163","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T17:02:12Z","timestamp":1736787732000},"page":"46-60","source":"Crossref","is-referenced-by-count":11,"title":["Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-1395","authenticated-orcid":false,"given":"Katharina","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4555-8334","authenticated-orcid":false,"given":"Alessa","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and 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,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lauseker","sequence":"additional","affiliation":[{"name":"Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, LMU Munich , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Bauer","sequence":"additional","affiliation":[{"name":"Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, LMU Munich , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-333X","authenticated-orcid":false,"given":"Nicole","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital 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GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-0296","authenticated-orcid":false,"given":"Katharina","family":"Schilbach","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kn\u00f6sel","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]},{"name":"Institute of Pathology, Faculty of Medicine, LMU Munich , 80337 Munich 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