title: Brief Report: Menopause and Primary Ovarian Insufficiency in Women Treated for Antineutrophil Cytoplasmic Antibody-Associated Vasculitides.
abstract: OBJECTIVE
  One of the side effects of cyclophosphamide is earlier menopause and primary ovarian insufficiency. This study was undertaken to investigate the onset of menopause and the incidence of primary ovarian insufficiency in women with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), especially after treatment with orally administered cyclophosphamide.
  
  
  METHODS
  We retrospectively studied the onset of menopause and the influence of cyclophosphamide in women diagnosed as having AAV in our center between 1970 and 2012.
  
  
  RESULTS
  Ninety-four premenopausal women diagnosed as having AAV were included. Sixty-seven patients received cyclophosphamide, and 27 received other, mostly immunosuppressive, medication. Forty-six cyclophosphamide-treated women developed menopause, 22 of whom were considered to have primary ovarian insufficiency. None of the patients who were not treated with cyclophosphamide developed primary ovarian insufficiency. There was a significant association between a cumulative cyclophosphamide dose of >16.6 gm, versus a cumulative dose of <16.6 gm, and menopause (χ(2)  = 8.72, P = 0.003; odds ratio [OR] 2.60 [95% confidence interval 1.38-4.90]). In addition, there was a significant association between a cumulative cyclophosphamide dose of <16.6 gm, versus no cyclophosphamide exposure, and menopause (χ(2)  = 16.37, P < 0.001; OR 7.32 [95% confidence interval 2.79-19.20]). Both women who received cyclophosphamide and those who did not experienced involuntary childlessness.
  
  
  CONCLUSIONS
  Earlier menopause and primary ovarian insufficiency frequently develop after oral cyclophosphamide therapy in premenopausal women with AAV. Involuntary childlessness is common after the development of primary ovarian insufficiency, but it also occurs in women not treated with cyclophosphamide. These findings emphasize the importance of the use of drugs that are not toxic to gonadal function in women of childbearing age.
authors.affiliation: University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Tuin
authors.affiliation: University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan-Stephan F
authors.initials: JS
authors.lastname: Sanders
authors.affiliation: University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: André P
authors.initials: AP
authors.lastname: van Beek
authors.affiliation: University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Hoek
authors.affiliation: University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
mesh_terms: D000328:Adult; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D001379:Azathioprine / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D060046:Maintenance Chemotherapy; D008593:Menopause; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011239:Prednisolone; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology*; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D011239:Prednisolone; D009173:Mycophenolic Acid; D001379:Azathioprine; D008727:Methotrexate