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Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations.

Authors
  • Abrahamsson, Gun1
  • Ekerhovd, Erling1
  • Janson, Per Olof1
  • Jansson, Svante2
  • Ahlman, Håkan2
  • Wängberg, Bo2
  • Norström, Anders1
  • 1 Institution of Clinical Sciences, Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. , (Sweden)
  • 2 Department of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. , (Sweden)
Type
Published Article
Journal
Acta Obstetricia Et Gynecologica Scandinavica
Publisher
Wiley (Blackwell Publishing)
Publication Date
Oct 01, 2020
Volume
99
Issue
10
Pages
1297–1302
Identifiers
DOI: 10.1111/aogs.13869
PMID: 32282928
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [3 H]thymidine in cultured granulosa cells. Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function. © 2020 Nordic Federation of Societies of Obstetrics and Gynecology.

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