title: Endometrial cancer in postmenopausal women using estradiol-progestin therapy.
abstract: OBJECTIVE
  To estimate the risk of endometrial cancer in all Finnish postmenopausal women using various forms of estradiol-progestin therapy.
  
  
  METHODS
  All Finnish women (aged more than 50 years) who had used estradiol-progestin therapy in 1994-2006 for at least 6 months (n=224,015) were identified from the national medical Reimbursement Registry and linked to the Finnish Cancer Registry. A total of 1,364 type I and 38 type II endometrial cancers were recorded by the end of 2006. The incidence of endometrial cancer in estradiol-progestin therapy users was compared with that in the general population in this cohort study.
  
  
  RESULTS
  The use of a continuous estradiol-progestin therapy regimen for 3 years or more was associated with a 76% reduction of the risk for type 1 cancer (95% confidence interval [CI] 6-60%). In contrast, the use of a sequential estradiol-progestin therapy regimen for at least 5 years was accompanied with a 69% elevation (95% CI 43-96%) if the progestin was added monthly, and with a significantly higher, 276% risk elevation (95% CI 190-379%) if progestin was added at 3-month intervals. Sequential regimens containing norethisterone acetate, medroxyprogesterone acetate or dydrogesterone administered orally showed no significant differences in the endometrial safety. Oral and transdermal norethisterone acetate were associated with similar risk elevations. Women using a monthly sequential estradiol-progestin regimen tended to be diagnosed with endometrial cancer in an earlier stage than the background population.
  
  
  CONCLUSIONS
  Use of a continuous rather than a sequential estradiol-progestin regimen decreases the risk of endometrial cancer, whereas the route of administration or type of progestin does not differ in terms of endometrial cancer risk.
  
  
  METHODS
  II.
authors.affiliation: From the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki; Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki; and Tempere School of Public Health, University of Tempere, Tempere, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Jaakkola
authors.forename: Heli
authors.initials: H
authors.lastname: Lyytinen
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Olavi
authors.initials: O
authors.lastname: Ylikorkala
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D004958:Estradiol / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects; D011372:Progestins / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D004967:Estrogens; D011372:Progestins; D004958:Estradiol