Young women with irregular menstrual periods may be at higher risk of developing—and dying from—ovarian cancer later in life, researchers found in a 50-year study of California women. The new research provides the first evidence linking abnormally long cycles or missed periods to higher ovarian cancer risk. It also challenges a longstanding hypothesis that such risk rises progressively with a woman’s total number of ovulations.

Having fewer ovulatory cycles is widely viewed as a protective factor against ovarian cancer. It’s the reason that hormonal birth control pills, pregnancy, and tubal ligations—which stop ovulation—have been thought to reduce risk for that disease. “This study is certainly curious, because it contradicts what we thought we knew about ovarian cancer and incessant ovulation,” says Mitchell Maiman, an OB/GYN at Staten Island University Hospital in New York.

Although ovarian cancer accounts for just 3% of all cancers in women, it’s the leading cause of gynecological cancer deaths. Less than half of all women diagnosed with ovarian cancer survive more than 5 years. Early symptoms, including abdominal discomfort and bloating, often go unnoticed or are misdiagnosed as irritable bowel syndrome. Because there are no routine screening tests and few markers to identify groups with increased risk of ovarian cancers, most cases are found when they are beyond the point of curing. Age is one risk factor—more than half of all ovarian cancers are diagnosed in women over the age of 63. Heredity is another—10% to 15% of women diagnosed with ovarian cancer have one or more known genetic risk factors.

To identify other risk factors, epidemiologist Barbara Cohn, director of the Public Health Institute’s Child Health and Development Studies in Oakland, California, and colleagues analyzed data from more than 15,000 California women who enrolled in a pregnancy study in 1959. That study sought to track disease risk over the lifetime of the mothers and their children. Menstrual irregularities—defined as a cycles lasting longer than 35 days or a long-term history of infrequent or missed periods—were reported at the beginning of the study, when the average age of the women was 26. Roughly 13% of the women reported irregular periods.

Over the next 50 years, 116 women developed ovarian cancer, 84 of whom died. Women with a history of menstrual irregularities were nearly twice as likely as women with normal periods to develop ovarian cancer and die from it by the age of 70. That link only increased with age, the researchers report in this month’s issue of the International Journal of Cancer. For example, women with menstrual irregularities were roughly three times as likely to develop and die from ovarian cancer by age 77 compared with women with normal periods. At that point in time, the risk from irregular periods was as large as the risk for women with a family history of the disease, Cohn says.

The researchers say it’s likely that many of the women in the study who developed ovarian cancer also suffered from a hormonal disorder called polycystic ovarian syndrome (PCOS). PCOS is often characterized by irregular or absent periods. But it’s impossible to know with certainty, because those diagnostic criteria were established after the start of the study. PCOS is a known risk factor for endometrial cancer, though previous studies investigating the link between PCOS and ovarian cancer have turned up mixed results—with some pointing toward increased risk, some pointing toward decreased risk, and others turning up no significant association.

Maiman says the new study could guide future research not only about who is at risk for ovarian cancer, but also about who might benefit from screening or prevention efforts. “If validated this could give us one more risk assessment factor to determine high-risk individuals in which screening is prudent.”

But designing such research will require more fine-grained answers several key questions, says Mia Gaudet, a cancer epidemiologist who is the strategic director for breast and gynecologic cancer research at the American Cancer Society in Atlanta. “Research is starting to show that the characteristics of those menstrual cycles may be more important than the number. For instance, were the periods heavier than someone who was cycling regularly? A study devised today would ask different questions,” Gaudet says. “[This is] a first step that warrants a closer look.”