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Evidence of Benefit


    The pathogenesis of ovarian carcinoma remains unclear. Several theories have been proposed to explain the epidemiology of ovarian cancer including the theory of "incessant ovulation,"[1,2] gonadotropin stimulation,[3] excess androgenic stimulation,[4] and inflammation.[5] Associated risk factors for ovarian cancer support some or all of these hypotheses. Oral contraceptive use is consistently associated with a decreased risk of ovarian cancer and may operate through preventing the trauma from repeated ovulation by lowering exposure to gonadotropins. No one theory, however, explains all the associated risk factors.

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    Protective Factors

    Factors associated with a decreased risk of ovarian cancer include: (1) using oral contraceptives, (2) having and breastfeeding children, (3) having a bilateral tubal ligation or hysterectomy, and (4) having a prophylactic oophorectomy.

    Oral contraceptives

    Multiple studies have consistently demonstrated a decrease in ovarian cancer risk in women who take oral contraceptives.[6,7] The protective association increases with the duration of oral contraceptive use and persists up to 25 years after discontinuing oral contraceptives. A review of the literature demonstrated a 10% to 12% decrease in risk associated with use for 1 year and an approximate 50% decrease after 5 years of use. This reduced risk was present among both nulliparous and parous women.[6] A protective association between oral contraceptives and risk of ovarian cancer has been observed in most studies [8,9,10] among women who carry a mutation in BRCA1 and BRCA2 genes. A population-based study conducted in Israel did not observe an association between oral contraceptives and ovarian cancer, but parity was protective.[11]

    Tubal sterilization

    In a prospective study, a 33% decrease in the risk of ovarian cancer among women who underwent tubal sterilization was observed after adjusting the data for oral contraceptive use, parity, and other ovarian cancer risk factors. This study also demonstrated a weaker, although statistically significant, decrease in risk associated with simple hysterectomy.[12]

    Prophylactic oophorectomy

    Prophylactic oophorectomy may reduce the risk of developing ovarian cancer for women at high risk. One group for whom this option is considered is women who have an inherited susceptibility to ovarian cancer such as women who have mutations in BRCA1, BRCA2, or hereditary nonpolyposis colon cancer (HNPCC)–associated genes. These women have a lifetime risk much higher than the general population, in the range of 20% to 60%. Evidence of the magnitude of risk reduction associated with bilateral oophorectomy comes primarily from studies of women with an inherited risk of cancer. A family-based study among women with BRCA1 or BRCA2 mutations found that of the 259 women who had undergone bilateral prophylactic oophorectomy, 2 (0.8%) developed subsequent papillary serous peritoneal carcinoma and 6 (2.8%) had stage I ovarian cancer at the time of surgery. Twenty-percent of the 292 matched controls who did not have prophylactic surgery developed ovarian cancer. Prophylactic surgery was associated with a greater than 90% reduction in the risk of ovarian cancer, (relative risk [RR] = 0.04; 95% confidence interval [CI], 0.01–0.16) with an average follow-up of 9 years;[13] however, family-based studies may be associated with biases due to case selection and other factors that may influence the estimate of benefit.[14] A study of 315 women with documented HNPCC–associated germline mutations found no ovarian cancer among 47 women who had bilateral salpingo-oophorectomy and 12 cases (5%) among women with mutations who had not had surgery for a prevented fraction of 100% (95% CI, 62%–100%). Prophylactic surgery, however, is not 100% effective. Case reports and case series have reported the occurrence of peritoneal carcinomatosis following oophorectomy.[15,16,17]


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