Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies

Ovarian cancer is the leading cause of mortality related to gynecologic malignancies in Sweden but there is no current screening program. Based upon epidemiological research there is evidence that certain reproductive factors are associated with ovarian cancer risk. Most studies generally indicate that each childbirth incurs a 15-20% risk reduction. Women who have used oral contraceptives for 5 years or longer experience about half the risk of ovarian cancer compared with never users. Breastfeeding seems to be protective while age at menarche and at menopause are less consistent risk predictors. Tubal ligation and hysterectomy seem to reduce ovarian cancer risk by up to 80%. Although some studies found endometriosis, polycystic ovarian syndrome (PCOS) and pelvic inflammatory disease (PID) to be positively related to ovarian cancer, the role of these factors is not yet established. Most recent studies observed an approximately 50% ovarian cancer risk increase among ever users of hormone replacement therapy (HRT) compared with never users, and the risk increased further with long-term use. There is less information concerning separate estrogen and progestin effects of HRT and ovarian cancer risk. Although the cause of ovarian cancer remains obscure, hypotheses relating to incessant ovulation, excessive gonadotropin secretion, retrograde carcinogen transportation, apoptosis and estrogen/progestin imbalance have been invoked as etiological explanations. All these hypotheses find various epidemiological support. The aim of this review is to summarize the epidemiological findings on reproductive factors and ovarian cancer risk. These findings are considered in the context of etiologic hypotheses and some new research areas are suggested.