PurposeThe purpose of this meta-analysis was to determine the strength of the association between gynecologic surgeries, tubal ligation and hysterectomy, and ovarian cancer.MethodsWe searched the PubMed, Web of Science, and Embase databases for all English-language articles dated between 1969 through March 2011 using the keywords “ovarian cancer” and “tubal ligation” or “tubal sterilization” or “hysterectomy.” We identified 30 studies on tubal ligation and 24 studies on hysterectomy that provided relative risks for ovarian cancer and a p-value or 95% confidence interval (CI) to include in the meta-analysis. Summary RRs and 95% CIs were calculated using a random-effects model.ResultsThe summary RR for women with vs. without tubal ligation was 0.70 (95%CI: 0.64, 0.75). Similarly, the summary RR for women with vs. without hysterectomy was 0.74 (95%CI: 0.65, 0.84). Simple hysterectomy and hysterectomy with unilateral oophorectomy were associated with a similar decrease in risk (summery RR = 0.62, 95%CI: 0.49-0.79 and 0.60, 95%CI: 0.47-0.78, respectively). In secondary analyses, the association between tubal ligation and ovarian cancer risk was stronger for endometrioid tumors (summary RR = 0.45, 95%CI: 0.33, 0.61) compared to serous tumors.ConclusionObservational epidemiologic evidence strongly supports that tubal ligation and hysterectomy are associated with a decrease in the risk of ovarian cancer, by approximately 26-30%. Additional research is needed to determine whether the association between tubal ligation and hysterectomy on ovarian cancer risk differs by individual, surgical, and tumor characteristics.

BackgroundMammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known.Methods and findingsWe examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35–85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (–0.46 cm [95% CI: −0.53, −0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was −0.24 cm (95% CI: −0.34, −0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (−0.38 cm [95% CI: −0.44, −0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature.ConclusionsDeclines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

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