{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:16:09Z","timestamp":1781774169916,"version":"3.54.5"},"reference-count":95,"publisher":"BMJ","issue":"9","funder":[{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2018,7,18]]},"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Hodgkin\u2019s lymphoma (HL) has become the prototype of a curable disease. However, many young survivors suffer from late adverse effects of treatment. Both chemotherapy (CT) and radiotherapy (RT) may induce primary ovarian insufficiency (POI), which has been associated with reduced bone mineral density (BMD), neurocognitive dysfunction and possibly cardiovascular disease (CVD). While the general assumption is that POI increases CVD risk, other hypotheses postulate reverse causality, suggesting that cardiovascular risk factors determine menopausal age or that biological ageing underlies both POI and CVD risk. None of these hypotheses are supported by convincing evidence. Furthermore, most studies on POI-associated conditions have been conducted in women with early natural or surgery-induced menopause with short follow-up times. In this study, we will examine the long-term effects of CT-induced and\/or RT-induced POI on BMD, cardiovascular status, neurocognitive function and quality of life in female HL survivors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This study will be performed within an existing Dutch cohort of HL survivors. Eligible women were treated for HL at ages 15\u201339 years in three large hospitals since 1965 and survived for \u22658 years after their diagnosis. Women visiting a survivorship care outpatient clinic will be invited for a neurocognitive, cardiovascular and BMD assessment, and asked to complete several questionnaires and to provide a blood sample. Using multivariable regression analyses, we will compare the outcomes of HL survivors who developed POI with those who did not. Cardiovascular status will also be compared with women with natural POI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>This study has been approved by the Institutional Review Board of the Netherlands Cancer Institute and has been registered at \u2018Toetsingonline\u2019 from the Dutch Central Committee on Research involving Human Subjects (file no. NL44714.031.13). Results will be disseminated through peer-reviewed publications and will be incorporated in follow-up guidelines for HL survivors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2017-018120","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T09:27:25Z","timestamp":1536658045000},"page":"e018120","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Rationale and design of a cohort study on primary ovarian insufficiency in female survivors of Hodgkin\u2019s lymphoma: influence on long-term adverse effects (SOPHIA)"],"prefix":"10.1136","volume":"8","author":[{"given":"Inge M","family":"Krul","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke W J","family":"Opstal-van Winden","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9e M","family":"Zijlstra","sequence":"additional","affiliation":[{"name":"Department of Haemato-oncology, VU University Medical Center, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolande","family":"Appelman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, VU University Medical Center, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne B","family":"Schagen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian J","family":"Meijboom","sequence":"additional","affiliation":[{"name":"Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Sern\u00e9","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, VU University Medical Center, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis B","family":"Lambalk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lips","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrine Section, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"van Dulmen-den Broeder","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Haematology, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hauptmann","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurien A","family":"Dani\u00ebls","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthe M P","family":"Aleman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora E","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"2025101812485199000_8.9.e018120.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa064601"},{"issue":"Suppl 1","key":"2025101812485199000_8.9.e018120.2","doi-asserted-by":"crossref","first-page":"S111","DOI":"10.1093\/annonc\/8.suppl_1.S111","article-title":"Patients with stage III\/IV Hodgkin\u2019s disease in partial remission after MOPP\/ABV chemotherapy have excellent prognosis after additional involved-field radiotherapy: interim results from the ongoing EORTC-LCG and GPMC phase III trial. 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