{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:59:12Z","timestamp":1791136752437,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Mitotane is an adrenolytic and anticortisolic drug used in adrenocortical carcinoma (ACC), Cushing's disease (CD), and ectopic ACTH syndrome. Its effects on the ovaries are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the ovarian and gonadotrope effects of mitotane therapy in premenopausal women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>We studied 21 premenopausal women (ACC:<jats:italic>n<\/jats:italic>=13; CD:<jats:italic>n<\/jats:italic>=8; median age 33 years, range 18\u201345 years) receiving mitotane at a median initial dose of 3\u200ag\/day (range 1.5\u20136\u200ag\/day).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gynecological history was collected and ovarian ultrasound was performed. Four women also underwent ovarian CT or magnetic resonance imaging. Serum gonadotropin, estradiol (E<jats:sub>2<\/jats:sub>), androgens, sex hormone-binding globulin (SHBG), and circulating mitotane levels were determined at diagnosis and during mitotane therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the women included, ovarian macrocysts (bilateral in 51%) were detected after a median 11 months (range: 3\u201336) of mitotane exposure. The median number of macrocysts per woman was two (range: 1\u20134) and the median diameter of the largest cysts was 50\u200amm (range: 26\u201390). Menstrual irregularities and\/or pelvic pain were present in 15 out of 21 women at macrocyst diagnosis. In two women, the macrocysts were revealed by complications (ovarian torsion and hemorrhagic macrocyst rupture) that required surgery. Mitotane therapy was associated with a significant decrease in androstenedione and testosterone levels and a significant increase in LH levels. Serum FSH and E<jats:sub>2<\/jats:sub>levels were also increased, and SHBG levels rose markedly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mitotane therapy causes significant morphological and ovarian\/gonadotrope hormonal abnormalities in premenopausal women. Follicular thecal steroid synthesis appears to be specifically altered and the subsequent increase in gonadotropins might explain the development of macrocysts. The mechanisms underlying these adverse effects, whose exact prevalence in this population still needs to be determined, are discussed.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-14-0670","type":"journal-article","created":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T07:09:05Z","timestamp":1416467345000},"page":"141-149","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":25,"title":["Ovarian macrocysts and gonadotrope\u2013ovarian axis disruption in premenopausal women receiving mitotane for adrenocortical carcinoma or Cushing's disease"],"prefix":"10.1093","volume":"172","author":[{"given":"Sylvie","family":"Salenave","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Bernard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Do","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Guignat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bachelot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Leboulleux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Droumaguet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Bry-Gauillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Pierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Crini\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Santulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Touraine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Chanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schlumberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Maiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Baudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"23","key":"1_28788020","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1056\/NEJMoa063360","volume":"356","author":"Terzolo","year":"2007","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"key":"2_49468731","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1200\/JCO.2009.27.5958","volume":"28","year":"2010","journal-title":"Journal of Clinical Oncology","ISSN":"https:\/\/id.crossref.org\/issn\/0732-183X","issn-type":"print"},{"issue":"9","key":"3_4715343","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1056\/NEJM197903013000903","volume":"300","author":"Luton","year":"1979","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"3","key":"4_42460704","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1517\/14728214.2012.679263","volume":"17","author":"Schteingart","year":"2012","journal-title":"Expert opinion on emerging drugs","ISSN":"https:\/\/id.crossref.org\/issn\/1472-8214","issn-type":"print"},{"issue":"9","key":"5_40285310","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1210\/jc.2011-0536","volume":"96","year":"2011","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"4","key":"6_43244961","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1530\/EJE-12-0358","volume":"167","year":"2012","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"3","key":"7_45848186","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1530\/ERC-12-0368","volume":"20","author":"Hescot","year":"2013","journal-title":"Endocrine-Related Cancer","ISSN":"https:\/\/id.crossref.org\/issn\/1351-0088","issn-type":"print"},{"issue":"12","key":"8_46534169","doi-asserted-by":"publisher","first-page":"4759","DOI":"10.1210\/jc.2013-2281","volume":"98","year":"2013","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"9522","key":"9_22134149","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1016\/S0140-6736(06)68699-6","volume":"367","author":"Newell-Price","year":"2006","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"issue":"2","key":"10_41122381","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1530\/EJE-11-0557","volume":"166","year":"2012","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"9","key":"11_6157982","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1210\/jc.83.9.3083","volume":"83","author":"Lado-Abeal","year":"1998","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"4","key":"12_32037848","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1677\/ERC-08-0103","volume":"15","year":"2008","journal-title":"Endocrine-Related Cancer","ISSN":"https:\/\/id.crossref.org\/issn\/1351-0088","issn-type":"print"},{"issue":"23","key":"13_42502935","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1056\/NEJMoa1200966","volume":"366","author":"Fassnacht","year":"2012","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"1","key":"14_42065825","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1093\/jnci\/29.1.127","volume":"29","year":"1962","journal-title":"JNCI Journal of the National Cancer Institute","ISSN":"https:\/\/id.crossref.org\/issn\/0027-8874","issn-type":"print"},{"issue":"5","key":"15_4347048","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S0090-9556(25)05972-0","volume":"5","author":"Martz","year":"1977","journal-title":"Drug Metabolism and Disposition","ISSN":"https:\/\/id.crossref.org\/issn\/0090-9556","issn-type":"print"},{"issue":"10","key":"16_15889126","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1016\/0006-2952(95)00028-X","volume":"49","author":"Cai","year":"1995","journal-title":"Biochemical pharmacology","ISSN":"https:\/\/id.crossref.org\/issn\/0006-2952","issn-type":"print"},{"key":"17_47939944","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.beem.2012.05.002","volume":"26","year":"2012","journal-title":"BEST PRACTICE RESEARCH CLINICAL ENDOCRINOLOGY METABOLISM"},{"issue":"2","key":"18_17588728","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1210\/er.2001-0031","volume":"24","author":"Labrie","year":"2003","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"issue":"8","key":"19_16167129","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1056\/NEJM199602223340805","volume":"334","author":"Latronico","year":"1996","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"11","key":"20_16520247","doi-asserted-by":"publisher","first-page":"3850","DOI":"10.1210\/jc.81.11.3850","volume":"81","author":"Toledo","year":"1996","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"2","key":"21_16683737","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/S0015-0282(97)81929-2","volume":"67","author":"Arnhold","year":"1997","journal-title":"Fertility and sterility","ISSN":"https:\/\/id.crossref.org\/issn\/0015-0282","issn-type":"print"},{"issue":"4","key":"22_10783554","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S0015-0282(98)00517-2","volume":"71","author":"Arnhold","year":"1999","journal-title":"Fertility and sterility","ISSN":"https:\/\/id.crossref.org\/issn\/0015-0282","issn-type":"print"},{"issue":"6","key":"23_6421446","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1046\/j.1365-2265.1999.00863.x","volume":"51","author":"Arnhold","year":"1999","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"issue":"6","key":"24_16726271","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1172\/JCI119284","volume":"99","author":"Fujieda","year":"1997","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"issue":"5","key":"25_16772558","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1210\/jc.82.5.1511","volume":"82","author":"Bose","year":"1997","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"5","key":"26_10621553","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1507\/endocrj.47.629","volume":"47","author":"Tanae","year":"2000","journal-title":"Endocrine journal","ISSN":"https:\/\/id.crossref.org\/issn\/0918-8959","issn-type":"print"},{"issue":"10","key":"27_16536271","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1093\/humrep\/","volume":"11","author":"Meirow","year":"1996","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"2","key":"28_18014903","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1093\/humrep\/deh065","volume":"19","author":"ten Kate-Booij","year":"2004","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"10","key":"29_22390192","doi-asserted-by":"publisher","first-page":"4179","DOI":"10.1210\/jc.2006-0469","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"6","key":"30_21809119","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1210\/jc.2005-2157","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"7","key":"31_17041397","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/S0039-128X(02)00014-4","volume":"67","author":"Bendridi","year":"2002","journal-title":"Steroids","ISSN":"https:\/\/id.crossref.org\/issn\/0039-128X","issn-type":"print"},{"issue":"1","key":"33_5587730","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1210\/edrv-11-1-80","volume":"11","author":"ROSNER","year":"1990","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"issue":"7","key":"34_4822888","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1210\/mend-1-7-465","volume":"1","author":"Steinkampf","year":"1987","journal-title":"Molecular Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0888-8809","issn-type":"print"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/172\/2\/141.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/172\/2\/141.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T19:47:13Z","timestamp":1747165633000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/172\/2\/141\/6660928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2]]},"references-count":33,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-14-0670","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2]]}}}