{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:17:05Z","timestamp":1788628625661,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100018502","name":"Kanazawa University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018502","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Brain Tumor Pathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Luteinizing hormone-releasing hormone (LHRH) agonists are widely used for androgen-deprivation therapy in prostate cancer. Recent reports have raised concern that LHRH may influence the biological behavior of LHRH receptor-expressing intracranial tumors, including meningiomas; however, clinical evidence remains limited. We describe two cases of rapidly progressive meningioma temporally associated with the initiation of leuprorelin acetate. Case 1 was a 67-year-old man with a left cerebellopontine angle meningioma that had demonstrated gradual enlargement over 26 months. Following the initiation of leuprorelin acetate, the tumor exhibited accelerated growth, necessitating surgical resection. Pathology confirmed a fibrous meningioma with LHRH and its receptor positive. Case 2 was a 72-year-old man previously treated with subtotal resection and radiotherapy for an atypical meningioma. After 6 years of radiographic stability, the tumor rapidly regrew soon after leuprorelin acetate initiation and required re-resection. Both the primary and recurrent tumors were LHRH- and LHRH receptor-positive. Freshly resected tumor tissue cultured ex vivo demonstrated a dose-dependent increase in cell viability following 7-day exposure to leuprorelin acetate. These findings suggest that LHRH agonists may be associated with increased cell viability in a subset of receptor-positive meningiomas. Caution is warranted when initiating LHRH agonist therapy in patients with known or suspected meningiomas.<\/jats:p>","DOI":"10.1007\/s10014-026-00548-0","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:01:27Z","timestamp":1788584487000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Meningioma enlargement associated with luteinizing hormone-releasing hormone agonist therapy: two cases and supporting in vitro evidence"],"prefix":"10.1007","author":[{"given":"Toshiya","family":"Ichinose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2148-8231","authenticated-orcid":false,"given":"Masashi","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Tamai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsutoshi","family":"Nakada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"548_CR1","doi-asserted-by":"publisher","first-page":"1137849","DOI":"10.3389\/fonc.2023.1137849","volume":"13","author":"V Yarabarla","year":"2023","unstructured":"Yarabarla V, Mylarapu A, Han TJ et al (2023) Intracranial meningiomas: an update of the 2021 World Health Organization classifications and review of management with a focus on radiation therapy. Front Oncol 13:1137849","journal-title":"Front Oncol"},{"key":"548_CR2","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1093\/neuonc\/noae239","volume":"27","author":"N Berghaus","year":"2025","unstructured":"Berghaus N, Hielscher T, Savran D et al (2025) Meningiomas: sex-specific differences and prognostic implications of a chromosome X loss. Neuro Oncol 27:1019\u20131028","journal-title":"Neuro Oncol"},{"key":"548_CR3","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.3171\/2023.3.JNS221838","volume":"139","author":"DF Miyagishima","year":"2023","unstructured":"Miyagishima DF, Sundaresan V, Gutierrez AG et al (2023) A systematic review and individual participant data meta-analysis of gonadal steroid hormone receptors in meningioma. J Neurosurg 139:1638\u20131647","journal-title":"J Neurosurg"},{"key":"548_CR4","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1076\/13813455199908107041QFT286","volume":"107","author":"R Durmaz","year":"1999","unstructured":"Durmaz R, Deliorman S, Isiksoy S et al (1999) Luteinizing hormone releasing hormone increases proliferation of meningioma cells in vitro. Arch Physiol Biochem 107:286\u2013291","journal-title":"Arch Physiol Biochem"},{"key":"548_CR5","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.clineuro.2008.09.015","volume":"111","author":"Y Hirota","year":"2009","unstructured":"Hirota Y, Tachibana O, Uchiyama N et al (2009) Gonadotropin-releasing hormone (GnRH) and its receptor in human meningiomas. Clin Neurol Neurosurg 111:127\u2013133","journal-title":"Clin Neurol Neurosurg"},{"key":"548_CR6","doi-asserted-by":"publisher","first-page":"6424","DOI":"10.3390\/ijms13056424","volume":"13","author":"H Tang","year":"2012","unstructured":"Tang H, Gong Y, Mao Y et al (2012) CD133-positive cells might be responsible for efficient proliferation of human meningioma cells. Int J Mol Sci 13:6424\u20136439","journal-title":"Int J Mol Sci"},{"key":"548_CR7","doi-asserted-by":"publisher","first-page":"300060522108289","DOI":"10.1177\/03000605221082895","volume":"50","author":"CP Chen","year":"2022","unstructured":"Chen CP, Lu X (2022) Gonadotropin-releasing hormone receptor inhibits triple-negative breast cancer proliferation and metastasis. J Int Med Res 50:3000605221082895","journal-title":"J Int Med Res"},{"key":"548_CR8","doi-asserted-by":"publisher","first-page":"e52530","DOI":"10.1371\/journal.pone.0052530","volume":"8","author":"G Lama","year":"2013","unstructured":"Lama G, Papi M, Angelucci C et al (2013) Leuprorelin acetate long-lasting effects on GnRH receptors of prostate cancer cells: an atomic force microscopy study of agonist\/receptor interaction. PLoS ONE 8:e52530","journal-title":"PLoS ONE"},{"key":"548_CR9","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1136\/jnnp.21.2.89","volume":"21","author":"ER Bickerstaff","year":"1958","unstructured":"Bickerstaff ER, Small JM, Guest IA (1958) The relapsing course of certain meningiomas in relation to pregnancy and menstruation. J Neurol Neurosurg Psychiatry 21:89\u201391","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"548_CR10","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s11060-009-0086-z","volume":"98","author":"P Guevara","year":"2010","unstructured":"Guevara P, Escobar-Arriaga E, Saavedra-Perez D et al (2010) Angiogenesis and expression of estrogen and progesterone receptors as predictive factors for recurrence of meningioma. J Neurooncol 98:379\u2013384","journal-title":"J Neurooncol"},{"key":"548_CR11","doi-asserted-by":"publisher","first-page":"611218","DOI":"10.3389\/fonc.2021.611218","volume":"11","author":"F Maiuri","year":"2021","unstructured":"Maiuri F, Mariniello G, de Divitiis O et al (2021) Progesterone Receptor Expression in Meningiomas: Pathological and Prognostic Implications. Front Oncol 11:611218","journal-title":"Front Oncol"},{"key":"548_CR12","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1002\/ijc.29274","volume":"136","author":"VS Benson","year":"2015","unstructured":"Benson VS, Kirichek O, Beral V et al (2015) Menopausal hormone therapy and central nervous system tumor risk: large UK prospective study and meta-analysis. Int J Cancer 136:2369\u20132377","journal-title":"Int J Cancer"},{"key":"548_CR13","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1200\/JCO.2007.14.2133","volume":"26","author":"S Blitshteyn","year":"2008","unstructured":"Blitshteyn S, Crook JE, Jaeckle KA (2008) Is there an association between meningioma and hormone replacement therapy? J Clin Oncol 26:279\u2013282","journal-title":"J Clin Oncol"},{"key":"548_CR14","doi-asserted-by":"publisher","unstructured":"Agopiantz M, Carnot M, Denis C et al (2023) Hormone receptor expression in meningiomas: a systematic review. Cancers (Basel) 15:980 https:\/\/doi.org\/10.3390\/cancers15030980","DOI":"10.3390\/cancers15030980"},{"key":"548_CR15","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/pcan.2013.45","volume":"16","author":"Q Li","year":"2013","unstructured":"Li Q, Coulson H, Klaassen Z et al (2013) Emerging association between androgen deprivation therapy and male meningioma: significant expression of luteinizing hormone-releasing hormone receptor in male meningioma. Prostate Cancer Prostatic Dis 16:387\u2013390","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"548_CR16","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/cncr.10647","volume":"95","author":"DJ Samson","year":"2002","unstructured":"Samson DJ, Seidenfeld J, Schmitt B et al (2002) Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma. Cancer 95:361\u2013376","journal-title":"Cancer"},{"key":"548_CR17","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/pcan.2011.50","volume":"15","author":"A Spitz","year":"2012","unstructured":"Spitz A, Young JM, Larsen L et al (2012) Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis 15:93\u201399","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"548_CR18","doi-asserted-by":"publisher","first-page":"327","DOI":"10.2176\/nmc.cr2012-0417","volume":"54","author":"T Anda","year":"2014","unstructured":"Anda T, Honda M, Ishihara T et al (2014) Progression of intracranial meningioma during luteinizing hormone-releasing hormone agonist treatment for prostate cancer: case report. Neurol Med Chir (Tokyo) 54:327\u2013330","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"548_CR19","first-page":"351","volume":"62","author":"KL Lee","year":"2003","unstructured":"Lee KL, Terris MK (2003) Luteinizing hormone-releasing hormone agonists and meningioma: a treatment dilemma. Urology 62:351","journal-title":"Urology"},{"key":"548_CR20","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.neuchi.2020.10.002","volume":"67","author":"L Nicosia","year":"2021","unstructured":"Nicosia L, Bucpapaj R, Barresi V et al (2021) Resected atypical meningioma relapsed to anaplastic meningioma during luteinizing hormone-releasing hormone agonist therapy. Neurochirurgie 67:193\u2013197","journal-title":"Neurochirurgie"},{"key":"548_CR21","doi-asserted-by":"publisher","first-page":"670e671","DOI":"10.1016\/j.wneu.2016.03.076","volume":"91","author":"T Tsutsui","year":"2016","unstructured":"Tsutsui T, Miyashita K, Sabit H et al (2016) Acute progression of recurrent meningioma during luteinizing hormone-releasing hormone agonist treatment for prostate cancer. World Neurosurg 91:670e671\u2013670e676","journal-title":"World Neurosurg"},{"key":"548_CR22","doi-asserted-by":"publisher","unstructured":"McKay MJ, Pandey R, Zadeh H et al (2022) Gonadotropin releasing hormone agonist-related meningioma progression causing abducens nerve palsy: an oncological case report. Precis Cancer Med 5:40 https:\/\/doi.org\/10.21037\/pcm-21-57","DOI":"10.21037\/pcm-21-57"},{"key":"548_CR23","doi-asserted-by":"publisher","first-page":"104154","DOI":"10.1016\/j.bas.2024.104154","volume":"5","author":"G Reuter","year":"2025","unstructured":"Reuter G, Potorac I, de Herdt C et al (2025) Recommendations on the management of meningioma and sex hormone therapy: the results of a collaborative effort between neurosurgical, endocrine and gynecological societies. Brain Spine 5:104154","journal-title":"Brain Spine"},{"key":"548_CR24","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1007\/s004010050458","volume":"91","author":"A Matsuno","year":"1996","unstructured":"Matsuno A, Fujimaki T, Sasaki T et al (1996) Clinical and histopathological analysis of proliferative potentials of recurrent and non-recurrent meningiomas. Acta Neuropathol 91:504\u2013510","journal-title":"Acta Neuropathol"},{"key":"548_CR25","first-page":"170","volume":"24","author":"SH Torp","year":"2005","unstructured":"Torp SH, Lindboe CF, Gronberg BH et al (2005) Prognostic significance of Ki-67\/MIB-1 proliferation index in meningiomas. Clin Neuropathol 24:170\u2013174","journal-title":"Clin Neuropathol"}],"container-title":["Brain Tumor Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10014-026-00548-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10014-026-00548-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10014-026-00548-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:02:34Z","timestamp":1788627754000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10014-026-00548-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":25,"alternative-id":["548"],"URL":"https:\/\/doi.org\/10.1007\/s10014-026-00548-0","relation":{},"ISSN":["1433-7398","1861-387X"],"issn-type":[{"value":"1433-7398","type":"print"},{"value":"1861-387X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]},"assertion":[{"value":"14 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Institutional Review Board of Kanazawa University Hospital (approval number:2023\u2009\u2212\u2009349 (114498)) and complied with all provisions of the World Medical Association Declaration of Helsinki. Informed consent was obtained from both patients for participation.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from both patients.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The data supporting the findings of this study are available from the corresponding author upon reasonable request, subject to applicable ethical and privacy restrictions.","order":4,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Declarations"}}]}}