title: Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix.
abstract: BACKGROUND
  Exogenous hormones may influence the development of cervical adenocarcinomas. Incidence rates of adenocarcinomas and use of noncontraceptive hormones have increased since the 1970s, but few studies have investigated this potential relationship.
  
  
  METHODS
  We conducted a multicenter case-control study of 124 women with adenocarcinomas, 139 women with squamous cell carcinomas matched on age, diagnosis date, clinic, and stage of disease (in situ or invasive) to adenocarcinoma cases, and 307 healthy community controls who were also matched on age, ethnicity, and residence to adenocarcinoma cases. Participants completed in-person interviews regarding exogenous hormone use before diagnosis and other risk factors and volunteered cervical samples for human papillomavirus (HPV) testing via a PCR-based method. Odds ratios (ORs) with 95% confidence intervals (CIs) estimated relative risks.
  
  
  RESULTS
  Only 13 adenocarcinoma cases (10.5%), 7 squamous carcinoma cases (5%), and 20 controls (6.5%) had used noncontraceptive hormones for menopausal symptoms, irregular periods, or disease prevention; most use was short-term, former use. Ever-use was associated with adenocarcinomas (OR = 2.1, 95% CI 0.95-4.6) but not squamous carcinomas (OR = 0.85, 95% CI 0.34-2.1). No trends were seen with duration of use or ages at first use, but unopposed estrogens were positively associated with adenocarcinomas (OR = 2.7). Unopposed estrogens remained associated with adenocarcinomas (OR = 2.0) when analyses were restricted to the HPV-positive controls. Menopausal status was not associated with adenocarcinomas or squamous carcinomas and did not modify the other associations.
  
  
  CONCLUSIONS
  Although small numbers warrant tentative conclusions, exogenous estrogens, especially unopposed estrogens, were positively associated with adenocarcinomas. Noncontraceptive hormones were negatively but weakly associated with squamous carcinomas.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Lacey
authors.forename: L A
authors.initials: LA
authors.lastname: Brinton
authors.forename: W A
authors.initials: WA
authors.lastname: Barnes
authors.forename: P E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: M D
authors.initials: MD
authors.lastname: Greenberg
authors.forename: O C
authors.initials: OC
authors.lastname: Hadjimichael
authors.forename: L
authors.initials: L
authors.lastname: McGowan
authors.forename: R
authors.initials: R
authors.lastname: Mortel
authors.forename: P E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: R J
authors.initials: RJ
authors.lastname: Kurman
authors.forename: A
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000209:etiology*; D016022:Case-Control Studies; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D018570:Risk Assessment; D002583:Uterine Cervical Neoplasms / Q000209:etiology*
chemical_list: D004967:Estrogens