Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer: Evidence Report / Technology Assessment Number 212

Ovarian cancer is the eighth most common cancer in women and is the fifth leading cause of cancer death, with an age-adjusted rate of 8.2 deaths per 100,000 women. Given current age-specific incidence and demographic projections, the number of cases of ovarian cancer will almost double over the next 35 years as women born between 1946 and 1964 (?baby boom? generation) reach the age of highest incidence (60 years & older). While advances in surgery, chemotherapy, and radiation therapy over the past 20 years have led to improved outcomes, overall 5-year survival is only 42% for ovarian cancer compared with 88% for breast cancer and 63% for colorectal cancer. The high mortality rate in women with ovarian cancer is largely attributed to the later stage at presentation compared with other common cancers. This has led to intense research efforts to identify effective screening strategies for ovarian cancer, but results have been disappointing, particularly with regard to decreases in mortality. There is consistent evidence from a variety of sources that oral contraceptive (OC) use reduces ovarian cancer risk. This evidence includes declining age-specific ovarian cancer incidence and mortality in cohorts of women who had access to OCs throughout their reproductive life, and there are several biologically plausible mechanisms for a protective effect. The potential benefit of using OCs solely to reduce the risk of ovarian cancer must be weighed with knowledge of other potential noncontraceptive health benefits of OCs and potential harms. The combination of systematic review and decision-analytic modeling presented in this report allows us to estimate the tradeoff between the harms and benefits of OC use for the overall population and for individual women, accounting for the potential influence of other factors, such as timing of OC use or presence of risk factors such as family history. This report was funded by the Centers for Disease Control and Prevention in conjunction with the Agency for Healthcare Research and Quality, and was designed to evaluate the benefits and harms of the use of oral contraceptives as a primary preventive measure against ovarian cancer. We focused on synthesizing the available evidence for the effectiveness of this strategy in a general population and in groups at elevated risk. We also evaluated benefits and harms of OC use that are not related to the development of ovarian cancer. Finally, we designed a comparative effectiveness model to inform the questions generated by this review. The Key Questions considered in this review are: KQ1: What is the effectiveness of combined (estrogen and progestin containing) and progestin-only OCs for reducing the risk of ovarian cancer? KQ2: Do specifics of OC use (e.g., dose/formulation, age at initiation, duration of use) affect the relative risk of developing ovarian cancer? KQ3: Does the use of OCs by specific populations of women (e.g., those defined by age, family history of breast and ovarian cancer, BRCA1/BRCA2 mutation status, parity) affect the relative risk of developing ovarian cancer? KQ4: Aside from pregnancy prevention, are there other benefits of OC use in reducing the risks of endometrial cancer or colorectal cancer? KQ5: What are the harms of OC use, including breast cancer incidence, cervical cancer incidence, venous thromboembolic disease, stroke, or myocardial infarction? How do these harms vary by dose or formulation, duration of use, or specific population? KQ6: Based on the comprehensive literature review, what are the benefits and harms from the use of OCs to reduce the incidence of ovarian cancer for specific populations? Based on the decision model, what is the estimated effect of these benefits and harms on life expectancy and quality-adjusted life expectancy? KQ7: Based on the systematic review and decision model, what research gaps need to be filled to better understand whether OCs are effective for the primary prevention of ovarian cancer?