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Although past studies have shown that oral contraceptives with 50 microg or more of estrogen reduce the risk of ovarian cancer, it is not clear whether newer, lower-dose formulations do as well. We conducted a population-based, case-control study in the Delaware Valley to assess the impact of dose of oral contraception on risk of ovarian cancer. Cases aged 20-69 years with a diagnosis of epithelial ovarian cancer ascertained between May 1994 and July 1999 (n = 767) were compared with community controls (n = 1,367). Compared with never users, the adjusted risk of ovarian cancer was reduced by 40% for oral contraceptive users overall, with longer duration of use affording greater protection. The ovarian cancer risk reduction was similar for women who initiated oral contraception before 1972, when high-dose pills dominated the market; between 1972 and 1980; and after 1980, when newer, lower-dose pills dominated. Oral contraceptive estrogen and progestin content were compared for cases and controls after adjustment for current age, number of pregnancies, race, and family history of ovarian cancer. Use of low-estrogen/low-progestin pills afforded an estimated risk reduction (odds ratio = 0.5, 95% confidence interval: 0.3, 0.6) that was identical to that for high-estrogen/high-progestin pills (odds ratio = 0.5, 95% confidence interval: 0.3, 0.7).

Previous epidemiologic observations consistently suggest that suppression of ovulation, tubal ligation, and hysterectomy reduce the risk of ovarian cancer and that perineal talc use increases the risk. We examined these and other risk factors in the context of a new hypothesis: that inflammation may play a role in ovarian cancer risk. Ovulation entails ovarian epithelial inflammation; talc, endometriosis, cysts, and hyperthyroidism may be associated with inflammatory responses of the ovarian epithelium; gynecologic surgery may preclude irritants from reaching the ovaries via ascension from the lower genital tract. We evaluated these risk factors in a population-based case-control study. Cases 20-69 years of age with a recent diagnosis of epithelial ovarian cancer (767) were compared with community controls (1,367). We found that a number of reproductive and contraceptive factors that suppress ovulation, including gravidity, breast feeding, and oral contraception, reduced the risk of ovarian cancer. Environmental factors and medical conditions that increased risk included talc use, endometriosis, ovarian cysts, and hyperthyroidism. Gynecologic surgery including hysterectomy and tubal ligation were protective. Tubal ligation afforded a risk reduction even 20 or more years after the surgery. The spectrum of associations provides support for the hypothesis that inflammation may mediate ovarian cancer risk.