Study Shows Risk of Death From Ovarian Cancer Linked to Overall Number of Ovulatory Cycles
By Kathleen Doheny
WebMD Health News
Reviewed by Louise Chang, MD

July 9, 2009 -- A woman's hormonal activity over her lifetime affects her risk of dying from ovarian cancer, according to a new study.

''From this study, it looks like having a higher number of lifetime ovulatory cycles and starting your period earlier, at a younger age, increase your risk of death after a diagnosis of ovarian cancer," says Cheryl L. Robbins, PhD, an epidemiologist at the CDC's division of reproductive health and the study's lead author.

Women who have been pregnant, for instance, have fewer ovulatory cycles over a lifetime than those who have not been pregnant.

This year, 21,550 new cases of ovarian cancer are expected in the U.S., and an estimated 14,600 women will die from the disease, according to the American Cancer Society.

Ovarian cancer is difficult to detect in early stages; only a fifth of all cases are detected when the cancer is still localized. Symptoms can include those often associated with less severe problems, such as abdominal bloating or swelling, urinary urgency, and pelvic pain -- and are thus often overlooked by women.
Study Details

While previous research has focused on risk factors for getting ovarian cancer -- including advancing age, obesity, and never becoming pregnant -- much less research has looked at risk factors that predict death once a diagnosis is made, Robbins tells WebMD.

For her study, she conducted an analysis of 410 women, ages 20 to 54, who were diagnosed with ovarian cancer and enrolled in the 1980-1982 Cancer and Steroid Hormone (CASH) study. After a follow-up with a median of 9.2 years (half followed longer, half less), 212 women died; 169 deaths were recorded as due to ovarian cancer.

Overall, the 15-year survival was 48% among the women study participants. Robbins and her team then looked at a host of reproductive factors including the number of pregnancies, use of oral contraceptives, breastfeeding history, age at first menstruation, whether the women had undergone hysterectomy, or whether they had their tubes tied.

The only reproductive factors that were statistically significant as predictors of dying from ovarian cancer were age at menstruation and the number of ovulatory cycles.

Those who had their first period before age 12 were 51% more likely to die from ovarian cancer compared to those who had their first period at age 14 or later.

In recent years, the age of first period has declined, Robbins and other say. For instance, Wright State University researchers recently found that girls born in the 1980s had an average age of 12.3 years when they had their first period. The study is published in the American Journal of Human Biology.

Women with the highest number of lifetime ovulatory cycles were 67% more likely to die of ovarian cancer than those in the group with the lowest number of cycles.

Other Opinions

The new study ''does suggest that some kind of hormonal factors that are tied into lifetime ovulatory cycles and age at menarche may play into a more aggressive ovarian cancer," says Andrew Li, MD, a gynecologic oncologist at Cedars-Sinai Medical Center, Los Angeles, and assistant professor of obstetrics and gynecology at the David Geffen School of Medicine at UCLA.

However, the study has several limitations, he tells WebMD. The women in the study may not be representative of a typical ovarian cancer patient, who is often diagnosed in her late 50s or 60s.

In the Robbins study, more than 74% of the women were 50 or younger.

The women in the study had been diagnosed from 1980 to 1982, Li notes, and today's treatments for ovarian cancer are different and improved.

While the study findings primarily point to a need for more research, ''this study would suggest taking oral contraceptive pills [earlier in life] would also improve [women's] survival should they be unfortunate enough to be diagnosed with ovarian cancer," Li says.

Both risk factors found to be associated with the higher risk of death from ovarian cancer in the study add up to more lifetime exposure to ovarian hormones, says Mary B. Daly, MD, PhD, director of the Personalized Cancer Risk Assessment Program at the Fox Chase Cancer Center in Philadelphia, who also reviewed the study for WebMD.

"This is the first time I've seen a study to relate those two factors to survival from ovarian cancer," Daly says.

Other research has found a consistent link between fewer ovulatory cycles and a lower risk of ovarian cancer, the researchers note, while research on the age at first period and ovarian cancer risk is inconsistent.

Daly, too, cites limitations in the study, also pointing out that the average age of the patients in the study is much younger than the typical average age of an ovarian cancer patient. "It is not exactly a representative population," she says.

There's no immediate take-home message for women, she says, but the study does pose an important question for researchers to answer next. And that is: "What is it about hormone exposure that can change the biology of ovarian cancer and make it more aggressive?"