Incessant ovulation and ovarian cancer - a hypothesis re-visited.

Ovarian cancer continues to be a silent killer. Most women have advanced disease at the time of diagnosis. Intensive efforts to develop effective screening strategies have not so far met with success. There is a need to re-visit the potential of prevention strategies. In 1971, the author submitted a hypothesis for a possible relationship between incessant ovulation and development of epithelial ovarian cancer. Subsequent research from different disciplines opened new frontiers to be explored for prevention in the general population and in high-risk groups, and for opportunistic interventions. The protective effect of oral contraceptive pills has been well documented. Widespread use of the pill in the past several decades is credited with a fall in the incidence of ovarian cancer in the general population, countering the effect of low parity. Removing the barriers against contraceptive access and satisfying the still unmet contraceptive need could expand the protective coverage. Enhanced understanding of the biological mechanisms involved in process of ovulation offers the promise of non-hormonal pharmacologic suppression of follicle rupture for women who have risk factors and do not need contraception. The evidence for a possible origin of epithelial cancer in the fimbria of the Fallopian tube presents an opportunity for preventive intervention, during hysterectomy, where salpingectomy alone may provide protection while one or both ovaries are conserved. Finally, the incessant ovulator egg-laying hen has demonstrated its potential as an experimental model for chemoprevention of epithelial ovarian cancer.