title: Ovulation-inducing drugs and ovarian cancer risk: results from an extended follow-up of a large United States infertility cohort.
abstract: OBJECTIVE
  To examine the relationship of ovulation-inducing drugs and ovarian cancer.
  
  
  METHODS
  Retrospective cohort study, with additional follow-up since initial report.
  
  
  METHODS
  Five large reproductive endocrinology practices.
  
  
  METHODS
  In a retrospective cohort of 9,825 women evaluated for infertility at five clinical sites in the United States between 1965 and 1988 with follow-up through 2010, we examined the relationship of ovulation-inducing drugs and ovarian cancer (n = 85).
  
  
  METHODS
  None.
  
  
  METHODS
  Hazard rate ratios (RR) and 95% confidence intervals (CI) for ovarian cancer.
  
  
  RESULTS
  Among women evaluated for infertility, there was no association of ovarian cancer risk with ever use of clomiphene citrate (CC) (adjusted RR 1.34, 95% CI 0.86-2.07) or gonadotropins (RR 1.00, 95% CI 0.48-2.08) and no evidence that any of several more detailed subgroups of usage were related to an increased risk with one exception: women who used CC and remained nulligravid did demonstrate much higher risks than those who successfully conceived compared with nonusers (respectively, RR 3.63, 95% CI 1.36-9.72 vs. RR 0.88, 95% CI 0.47-1.63).
  
  
  CONCLUSIONS
  Our overall results were reassuring and consistent with other studies. A reason for an association between CC use and ovarian cancer among persistently nulligravid women remains to be determined. Given the large and increasing number of women treated with ovulation-inducing drugs, the increased risk of ovarian cancer among the subset of women who remained nulligravid should be further monitored.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. Electronic address: britton.trabert@nih.gov.
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.forename: Emmet J
authors.initials: EJ
authors.lastname: Lamb
authors.forename: Bert
authors.initials: B
authors.lastname: Scoccia
authors.forename: Kamran S
authors.initials: KS
authors.lastname: Moghissi
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Westhoff
authors.forename: Shelley
authors.initials: S
authors.lastname: Niwa
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
mesh_terms: D000328:Adult; D015984:Causality; D002996:Clomiphene / Q000008:administration & dosage*; D015331:Cohort Studies; D015897:Comorbidity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage; D005500:Follow-Up Studies; D006062:Gonadotropins / Q000008:administration & dosage*; D006801:Humans; D015994:Incidence; D007247:Infertility, Female / Q000453:epidemiology* / Q000628:therapy*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology*; D010062:Ovulation Induction / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D005300:Fertility Agents, Female; D006062:Gonadotropins; D002996:Clomiphene
keywords: Ovarian cancer; clomiphene citrate; gonadotropins; infertility; risk