Oral Contraceptive Use For The Primary Prevention Of Ovarian Cancer

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?

Evaluates evidence for an increased risk of cancer in women using combined oral contraceptives, progestogen-only hormonal contraceptives, post-menopausal estrogen therapy, and post-menopausal estrogen-progestogen therapy. Although the carcinogenicity of these preparations has been extensively investigated, the book stresses the many complex methodological issues that must be considered when interpreting findings and weighing results. Evidence of an association between use of these preparations and positive effects on health, including a reduced risk of some cancers, is also critically assessed. The first and most extensive monograph evaluates evidence of an association between the use of combined oral contraceptives and cancer at nine sites. Concerning breast cancer, the evaluation concludes that, even if the association is causal, the excess risk for breast cancer associated with patterns of use that are typical today is very small. Studies of predominantly high-dose preparations found an increased risk of hepatocellular carcinoma in the absence of hepatitis viruses. Citing these findings, the evaluation concludes that there is sufficient evidence in humans for the carcinogenicity of combined oral contraceptives. The evaluation also found sufficient evidence for the carcinogenicity of some, but not all, combined preparations in animals. Combined oral contraceptives were classified as carcinogenic to humans. The evaluation also cites conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium. Progestogen-only contraceptives are evaluated in the second monograph, which considers the association with cancer at six sites. The evaluation found no evidence of an increased risk for breast cancer. Although the evaluation found sufficient evidence in animals for the carcinogenicity of medroxyprogesterone acetate, evidence for the carcinogenicity of progestogen-only contraceptives in humans was judged inadequate. Progestogen-only contraceptives were classified as possibly carcinogenic to humans. The third monograph, on post-menopausal estrogen therapy, considers evidence of an association with cancer at eight sites. Findings from a large number of epidemiological studies indicate a small increase in the risk of breast cancer in women who have used these preparations for five years or more. Studies consistently show an association between use of post-menopausal estrogen therapy and an increased risk for endometrial cancer. Data on the association with other cancers were either inconclusive or suggested no effect on risk. The evaluation concludes that post-menopausal estrogen therapy is carcinogenic to humans. The final monograph evaluates the association between the use of post-menopausal estrogen-progestogen therapy and cancer at four sites. The evaluation of limited data on breast cancer found an increased relative risk observed with long-term use. Data were judged insufficient to assess the effects of past use and of different progestogen compounds, doses, and treatment schedules. For endometrial cancer, the evaluation found an increase in risk relative to non-users when the progestogen was added to the cycle for 10 days or fewer. Post-menopausal estrogen-progestogen therapy was classified as possibly carcinogenic to humans. Concerning post-menopausal therapy in general, the book notes that evidence of carcinogenic risks must be placed in perspective of potential benefits. The prevention of osteoporotic fractures is cited as the best-established benefit. Evidence also suggests that estrogen prevents heart disease and may prevent memory loss and dementia.

Ovarian cancer management is a rapidly changing field with new treatment agents available as a result of a greater understanding of the pathogenesis of this disease. In addition, both surgical and chemotherapeutic treatment strategies are evolving to maximise response in this disease. This book brings together leading specialists from around the world to discuss and outline a variety of new concepts in ovarian cancer, ranging from molecular biology and genetics through screening to both surgical and chemotherapeutic management.

This highly informative and clearly written book presents the basic science and the latest data on hereditary breast and ovarian cancer (HBOC) to provide an up-to-date and holistic overview of the disease. It starts off by presenting the molecular mechanisms, genetic testing and counseling, and variants of unknown significance (VUS) to help readers understand the contemporary interpretation of the disease. Further chapters focus on the surveillance, diagnosis and treatment, including chemoprevention, risk reduction and drug development based on molecular mechanisms. It also includes a chapter on the latest findings from the HBOC database, ethical issues and the parp inhibitors, and discusses innovative thinking to manage and understand the disease. Hereditary Breast and Ovarian Cancer - Molecular Mechanism and Clinical Practice offers breast surgeons, medical oncologists, gynecological oncologists and genetic counselors a comprehensive overview of the disease. Providing insights into recent scientific findings and further avenues for investigation, it is also a thought-provoking and informative read for researchers and scholars.

"The definitive reference for budding and experienced cancer epidemiologists alike." -American Journal of Epidemiology "Practitioners in epidemiology and oncology will find immense value in this." -JAMA Since its initial publication in 1982, CANCER EPIDEMIOLOGY AND PREVENTION has served as the premier reference work for students and professionals working to understand the causes and prevention of cancer in humans. Now revised for the first time in more than a decade, this fourth edition provides a comprehensive summary of the global patterns of cancer incidence and mortality, current understanding of the major causal determinants, and a rationale for preventive interventions. Special attention is paid to molecular epidemiologic approaches that address the wider role of genetic predisposition and gene-environment interactions in cancer etiology and pathogenesis. New and timely chapters on environmental and social-epidemiologic factors include: · The role of social class disparities · The role of obesity and physical inactivity · The potential effects of electromagnetic fields and radiofrequency radiation · The principles of cancer chemoprevention For both seasoned professionals and newer generations of students and researchers, this fourth edition of CANCER EPIDEMIOLOGY AND PREVENTION remains the authority in the field -- a work of distinction that every lab, library, student, professional, or researcher should have close at hand.

This document is one of two evidence-based cornerstones of the World Health Organization's (WHO) new initiative to develop and implement evidence-based guidelines for family planning. The first cornerstone, the Medical eligibility criteria for contraceptive use (third edition) published in 2004, provides guidance for who can use contraceptive methods safely. This document, the Selected practice recommendations for contraceptive use (second edition), provides guidance for how to use contraceptive methods safely and effectively once they are deemed to be medically appropriate. The recommendations contained in this document are the product of a process that culminated in an expert Working Group meeting held at the World Health Organization, Geneva, 13-16 April 2004.