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In a nationwide prospective cohort study of Danish women who turned 50 years old between 1995 and 2002 [1], 909,946 women were eventually included in the analysis; 575,883 were never-users of HRT and 334,063 were ever-users. During an average follow-up of 8 years, there were 3068 ovarian cancers of which 2681 were epithelial tumors.

Ever-use of HRT was associated with an increased risk of ovarian cancer of 1.38 (95% confidence interval (CI) 1.26–1.51). The risk declined with years since last use and had disappeared after 2 years. The risk of epithelial ovarian cancer was 1.44 (95% CI 1.30–1.58). There was no significant difference between risk for users of estrogen-only therapy compared with combined estrogen plus progestin therapy and there was no significant difference in risk between those taking continuous or cyclic progestin. There was a non-significant trend to a lesser risk for women using transdermal estrogen compared to oral estrogen; however, the trend was reversed for transdermal compared to oral estrogen plus progestin therapy. There was no effect of dose or duration of therapy and no effect of age. The estimated absolute increase in risk of ovarian cancer for users of hormone replacement therapy (HRT) was 0.52 per 1000 woman-years compared to 0.40 per 1000 woman-years for non-users. This equates to one extra case per approximately every 8300 women taking HRT.


  • Rod Baber
    Associate Professor of Obstetrics and Gynaecology, Sydney Medical School, The University of Sydney, Australia
  • Alastair MacLennan
    Professor and Head of Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Australia


  1. Mørch LS, Løkkegaard E, Andreasen AH, Krüger-Kjaers S, Lidegaard O. Hormone therapy and ovarian cancer. JAMA 2009;302:298-305. Published July 15, 2009.
  2. Anderson GL, Judd HL, Kaunitz AM, et al. Effect of estrogen plus progestin on gynecological cancers and associated procedures: the Womens Health Initiative randomized trial. JAMA 2003;290:1739-48.
  3. Beral V, Bull D, Green J, et al. for The Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in The Million Women Study. Lancet 2007;369:1703-10.
  4. Zhou Bo, Sun Q, Cong R, et al. Hormone replacement therapy and ovarian cancer risk: a meta-analysis. Gynecol Oncol 2008;108:641-51.
  5. Pike MC, Pearce CL, Peters R, et al. Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study. Fertil Steril 2004;82:186-95.
  6. Moorman PG, Schildkraut JM, Calinquaert B, Halabi S, Berchuck A. Menopausal hormones and risk of ovarian cancer. Am J Obstet Gynecol 2005;193:76-81.
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