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Many of us were exposed to the news in mid-February that a meta-analysis by Beral and colleagues [1] published in [i]The Lancet[/i] concluded that even a short-term use (< 5 years) of postmenopausal hormone therapy (HT) is associated with increased risk for ovarian cancer. Analyses used individual participant datasets from 52 epidemiological studies. The principal analyses involved the prospective studies (with last HT use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. During [b]prospective[/b] follow-up, 12,110 postmenopausal women, 55% (6601) of whom had used HT, developed ovarian cancer. Among women last recorded as current users, risk was increased even with < 5 years of use (RR 1.43, 95% CI 1.31–1.56; [i]p[/i] < 0.0001). Risk was significantly increased in women who had been recent HT users (any duration, but stopped < 5 years before diagnosis) (RR 1.23, 95% CI 1.09–1.37; [i]p[/i] = 0.0006). Risk decreased the longer ago HT had last been used, although women who had used HT for at least 5 years (median duration 9 years) and then stopped were still at significantly increased risk more than 5 years (median time since last use 10 years) later (RR 1.10, 95% CI 1.01–1.20; [i]p[/i] = 0.02). Combining current or recent use resulted in an RR of 1.37 (95% CI 1.29–1.46; [i]p[/i] < 0.0001); this risk was similar in European and American prospective studies and for estrogen-only and estrogen–progestin preparations, but differed across the four main tumor types (heterogeneity, [i]p[/i] < 0•0001), being definitely increased only for the two most common types, serous (RR 1.53, 95% CI 1.40–1.66; [i]p[/i] < 0.0001) and endometrioid (RR 1.42, 95% CI 1.20–1.67; [i]p[/i] < 0.0001). Age at initiation of HT had little effect. The increased risk may well be largely or wholly causal; if it is, women who use HT for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.


  • Anne Gompel
    Unité de Gynécologie Endocrinienne, Université Paris Descartes, APHP, Cochin Port Royal, Paris, France
  • Samuel Shapiro
    Department of Public Health and Family Medicine, University of Cape Town, South Africa


  1. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet 2015; Feb 12. Epub ahead of print
  2. Beral V, Reeves G, Green J, Bull D, for the Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007;369:1703-10
  3. Mørch LS, Løkkegaard E, Andreasen AH, Krüger-Kjaer S, Lidegaard O. Hormone therapy and ovarian cancer. JAMA 2009;302:298-305
  4. Pearce CL, Chung K, Pike MC, Wu AH. Increased ovarian cancer risk associated with menopausal estrogen therapy is reduced by adding a progestin. Cancer 2009;115:5319
  5. Shapiro S. False alarm: postmenopausal hormone therapy and ovarian cancer. Climacteric 2007;10:466-9
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