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NASHVILLE, TN -- Medical prevention of ovarian cancer may be possible for all women in the future, according to Duke Comprehensive Cancer Center researchers. They report finding a second biologic pathway in monkeys that helps explain birth control pills' protective effect against ovarian cancer.

The results of new laboratory research indicate that the pills' protective effect is not due solely to preventing ovulation, suggesting that chemoprevention of ovarian cancer could be extended to women who are not ovulating or who are not interested in contraception, said Dr. Gustavo Rodriguez. He prepared the study findings for presentation March 4 at the annual meeting of the Society of Gynecologic Oncologists.

"Long-term survival of ovarian cancer patients has only improved modestly in the last decade, despite intensive research efforts, so prevention may represent the best hope for reducing mortality in the future," said Rodriguez, associate professor of gynecologic oncology.

The new study builds on the researchers' previous analysis of ovaries from monkeys, which found that progestin, which is a component of birth control pills, stimulates damaged cells on the ovary surface to begin committing cellular suicide in a process called apoptosis, effectively eradicating the very cells most likely to become cancerous.

Now the scientists report that progestin-exposed surface cells also produce higher amounts of a certain protein, called TGF-beta, that is known to be involved in several cancer-preventing cellular pathways. In addition, the amounts of TGF-beta in the progestin-exposed ovaries correlated well with the percentage of cells undergoing suicide.

"If, as our results indicate, the protective effect of oral contraceptives is not simply due to inhibiting ovulation, then chemoprevention of ovarian cancer could be applicable to all women, whether they are ovulating or not," said Rodriguez.

Routine use of oral contraceptives for just three years reduces a woman's risk of eventually developing ovarian cancer by as much as 50 percent, but only reduces her number of lifetime ovulations by about 10 percent, Rodriguez said. The protective effect of pregnancy is even greater, in that the first pregnancy lowers subsequent ovarian cancer risk by over 30 percent, he added.

"The protective effects of oral contraceptives and pregnancy are quite remarkable and much greater than expected from just preventing ovulation, so we began looking for biologic explanations," said Rodriguez. "We have now identified two biologic mechanisms by which the progestin component of birth control pills actively protects against ovarian cancer."

The ovarian tissue came from monkeys included in a three-year Wake Forest University School of Medicine study of a particular birth control pill and its estrogen and progestin components.

The Wake Forest study was funded by the National Institutes of Health. Rodriguez's analysis of the ovarian tissue of these monkeys was funded in part by the Department of Defense.

Co-authors on the study are Nimesh Nagarsheth, David Walmer, Rex Bentley, Regina Whitaker, Pam Eisner, Richard Dodge and Claude Hughes of Duke University Medical Center and Mark Cline of Wake Forest University School of Medicine, Winston-Salem, N.C.

Approximately 25,000 new cases of ovarian cancer are expected each year in the United States. The disease claims the lives of more than 14,000 American women annually, largely because there is no useful screening method and symptoms usually only occur at an advanced stage when the disease can be difficult to treat effectively.