Since they were first licensed nearly 50 years ago, birth control pills containing estrogen have prevented some 200,000 cases of ovarian cancer world-wide, estimate the authors of a study published January 26 in The Lancet. Further, in the absence of having taken oral contraceptives, half of these women would have died of the disease.

The researchers showed that oral contraceptives (OCs) continue to confer protection for years - even decades - after women stop using them. Thus, they surmise, "the number of ovarian cancers prevented [will] rise over the next few decades" to at least 30,000 each year.

These figures emerge from a comprehensive meta-analysis based on prospective and case-control data from 45 epidemiological studies in 21 countries, mostly in Europe and the United States. "These findings set a new standard in prevention for a deadly cancer," wrote the editors of The Lancet, "and have important public health implications."

The results showed that women who had ever taken OCs were 27 percent less likely to develop ovarian cancer. The studies included 23,257 women with ovarian cancer, 31 percent of whom had taken OCs; of the 87,303 controls, 37 percent took OCs.

Two trends emerged that were really striking, according to Dr. Beth Karlan, editor-in-chief of Gynecologic Oncology and director of the Gilda Radner Cancer Detection Program at Cedars-Sinai Outpatient Cancer Center in Los Angeles. First, the longer OCs were used, the greater the ovarian cancer risk reduction, decreasing about 20 percent for each 5 years of use.

The second clear trend was the duration of the protective effects, which lasted long after women had stopped using OCs. For each 5 years of use, risk of developing ovarian cancer was reduced 29 percent in the first 10 years after stopping. The risk reduction was still significant though smaller (19 percent) for years 10–20, and smaller still (15 percent) 20–29 years after discontinuation.

Another feature of these results is their uniformity. OCs seem to protect against nearly all types of epithelial and nonepithelial tumors, with the possible exception of mucinous ovarian cancer (which accounted for only 12 percent of cases studied in the meta-analysis). The Lancet editorial points out that the results show "the benefits of oral contraceptives are independent of the preparation [estrogen dose], and vary little by ethnic origin, parity, family history of breast cancer, body-mass index, and use of hormone replacement therapy."

Representatives from nearly all of these studies - including Drs. Patricia Hartge, James Lacey, Louise Brinton, and Robert Hoover from the Epidemiology and Biostatistics Program in NCI's Division of Cancer Epidemiology and Genetics (DCEG) - worked together to ensure the integrity of the analysis, forming the Collaborative Group on Epidemiological Studies of Ovarian Cancer, under the leadership of Dr. Valerie Beral and colleagues at Oxford University's Cancer Research UK Epidemiology Unit.

The absence of proven screening methods for ovarian cancer make these findings all the more welcome. But the issue is not straightforward, because calculating "the net effect on women's health is fraught with uncertainties," wrote Drs. Eduardo L. Franco and Eliane Duarte-Franco of McGill University in Montreal in a comment accompanying the article. They went on to list possible side effects of OCs as increased risk of thromboembolism, heart disease, migraine, liver disease, and several other relatively uncommon conditions.

The analyses were not focused on comparing the benefits and risks of OCs, explains DCEG's Dr. Brinton, but only examined their effect on ovarian cancer risk. In the absence of detailed risk-benefit data, including currently unknown risks, such as cancers in women who have taken OCs and later take long-term hormone replacement therapy, she says, "This meta-analysis does not recommend widespread prescription of OCs as a preventative measure against ovarian cancer."

Dr. Beral commented that while OCs may pose a slight increased risk of breast and cervical cancer, the effect is small and disappears once the drugs are no longer being used, as contrasted with the ongoing protective effect against ovarian cancer.

Dr. Karlan added, "Ovarian cancer remains a disease with a high mortality due [mainly] to our inability to reliably diagnose it at an early stage. Women are concerned about this risk." She noted that it is important for women to be aware that OCs reduce that risk when discussing their contraceptive choices with their health care providers.

—Addison Greenwood