NEWS & VIEWS REPRODUCTIVE ENDOCRINOLOGY

Menopausal hormone therapy —ovarian cancer risk revisited Susan R. Davis and Rodney Baber Refers to Collaborative Group on Epidemiological Studies of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet doi:10.1016/S0140‑6736(14)61687‑1

A large meta-analysis of 52 observational studies, conducted in multiple countries, suggests that menopausal hormone therapy (MHT) increases the risk of ovarian cancer. Should women who are taking MHT, either as estrogen alone or as estrogen combined with a progestogen, and their doctors be worried? Ovarian cancer, which includes several different cancer subtypes, is an uncommon cancer that predominantly affects older women. In 2011, the European agestandardized incidence of ovarian cancer was 3.5:10,000 per year for women aged 50–64 years and 6.5:10,000 per year for those aged ≥65 years.1 Parity, hysterectomy, tubal ligation and use of the oral contraceptive pill all influence the risk of ovarian cancer;2 however, an effect of menopausal hormone therapy (MHT) has not been clearly established. A central analysis of individual data collected from 52 observational studies, which collected information on MHT use and ovarian cancer incidence, now suggests that MHT use is associated with a statistically significant increase in serous and endometrioid ovarian cancers, and a significantly reduced incidence of the comparatively rarer mucinous and clear-cell ovarian cancers.3 The investigators, from the Collaborative Group on Epidemiological Studies of Ovar­ ian Cancer, methodically searched the literature to identify studies that could pro­ vide data for their analyses. Prospec­t ive and retro­spective studies, and Euro­p ean and North American studies, were ana­ lysed separately, and data were weighted in accordance with study size. The investigators reported a risk of ovarian cancer associated with ever-use of MHT compared with never-use, which was statistically significant for the prospective studies (RR 1.20, 95% CI 1.13–1.28) and across all studies (RR 1.14, 95% CI 1.09–1.20); however, no significant risk of ovarian cancer associated

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…this new meta-analysis is not a signal for women to cease using MHT…

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with MHT use was found in the retrospective studies (RR 1.02, 95% CI 0.93–1.11).3 Although subgroup analyses were performed, the investigators specifically highlighted the finding that the observed risk of ovarian cancer was greatest for a group of women who, at diagnosis, were either current MHT users, or had ceased using MHT within the 5 years before diagnosis. In absolute terms, the increase in risk was of the order of 2.4 additional cases per 10,000 women per year, although this number varied slightly with the age of the women included in the analyses. The major limitation of all meta-analysis is the completeness of the available data. For this study,3 classification of exposure to MHT was problematic, as individual women not only vary the medication they take, but also stop and start treatment unpredictably. The data for women aged

Reproductive endocrinology: Menopausal hormone therapy-ovarian cancer risk revisited.

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