Oral contraceptives have prevented some 100,000 ovarian cancer deaths worldwide over the past five decades, a meta-analysis here found.
The overall relative risk for ovarian cancer among women who had ever used oral contraceptives compared with never-users, was 0.73 (95% CI 0.70 to 0.76; P<0.0001), reported Valerie Beral, M.B.B.S., and colleagues at Cancer Research UK, in the January 26 issue of The Lancet.
The researchers said that, overall, ovarian cancer rates in women younger than 75 are 13% lower in the current decade than if oral contraceptives had never been available.
They estimated that 200,000 cases of ovarian cancer and 100,000 deaths have been prevented worldwide by oral contraceptive use since the birth control pill was first introduced in 1960.
“Use of oral contraceptives confers long-term protection against ovarian cancer,” the researchers concluded.
In an interview, Dr. Beral said that oral contraceptives suppress ovarian activity, thereby reducing the likelihood of malignant growth.
Her group based their findings on pooled data from 45 epidemiology studies conducted around the world, covering 23,257 women with ovarian cancer and 87,303 healthy controls, mainly in the industrial democracies.
Studies with at least 100 women that collected data on each participant’s reproductive history and contraceptive use were included; investigators from these studies participated in the collaborative. The authors identified 48 eligible studies but were unable to gather individual data from three.
Dr. Beral said the included studies represent “almost everything done to date on the association between use of the pill and ovarian cancer.”
The data indicated that 31% of women with ovarian cancer and 37% of healthy controls in the 45 studies had used oral contraceptives at some point in their lives.
The overall relative risk of developing ovarian cancer decreased by 20% for each five years of use (95% CI 18% to 23%, P<0.0001). For those who stayed on oral contraceptives for 15 years, Dr. Beral and colleagues wrote, the risk declined by half.
Among women who had used oral contraceptives and subsequently developed ovarian cancer, the mean time elapsed between last use and cancer diagnosis was 18.6 years.
The researchers found a highly linear relationship between the time of last use and the relative risk of developing ovarian cancer, ranging from 0.57 (95% CI 0.50 to 0.64) for those with last use within 10 years to 0.86 (95% CI 0.76 to 0.97) for those whose last use was 30 or more years previously.
When the data were adjusted for duration of use and time since last use, no other use-related factor significantly affected the cancer risk. The researchers examined age at first or last use as well as use before or after a child’s birth.
They also sought to determine if average estrogen doses in oral contraceptives influenced the cancer risk. The estrogen content in most contraceptives declined by more than half from the 1960s to the 1980s.
Because the data did not include specific information on estrogen doses, the researchers calculated the halfway point between first and last use of contraceptives for each participant (sufficient data were available for 14,703 cases and 51,908 controls) as a surrogate indicator.
The group found that, among contraceptive users who developed ovarian cancer, the mid-year of use for almost 40% was in the 1960s and for 13% it was in the 1980s.
But the relative risk was the same (0.70) for 1960s and 1980s users whose last use was 10 to 19 years previously, suggesting that average dose was not a significant influence.
Data on histological tumor subtype were available for 74% of the cancer cases. Risk reductions associated with oral contraceptives were similar for all subtypes except for mucinous tumors. Contraception seemed to have no effect on rates of the latter type, which accounted for 12% of cases, the researchers found
Factors including ethnic origin, alcohol and tobacco use, body mass index, use of hormone replacement therapy, education, and age at menarche did not significantly affect the risk reduction associated with contraceptive use.
Dr. Beral said the data suggested the protective effect did not vary geographically or ethnically. “It was across the board,” she said.
“In middle-income and low-income countries, oral contraceptives have probably had little effect so far on ovarian cancer incidence, since use was uncommon until the 1980s,” Dr. Beral and colleagues wrote.
Use in those countries has since risen dramatically, they said, and women in those countries accounted for about 75% of oral contraceptive users worldwide in 2002.
“With this number of oral contraceptive users and current ovarian cancer incidence rates, the number of ovarian cancers prevented would rise over the next few decades to about 30,000 every year,” according to the researchers.
“However, the number prevented is likely to be still greater since the prevalence of oral contraceptive use in middle-income and low-income countries is predicted to increase.”
In an accompanying commentary, Eduardo L. Franco, Dr.P.H., and Eliane Duarte-Franco, M.D., of McGill University, called the study “a major contribution to our understanding of the role of oral contraceptives in the causation or prevention of ovarian cancer.”
The study, they said, “tackled many questions about the quantitative effects of oral contraceptive use, age at start, duration of use, time since cessation, and era of use, all in finely stratified analyses that accounted for key a priori confounders and design variables.”
Dr. Beral declined to suggest that women should consider taking oral contraceptives in order to prevent ovarian cancer.
“We’re in the business of providing the data. We’re not in the business of making recommendations,” she said.
In an unsigned editorial, Lancet editors also stopped short of making an overt recommendation, but they said women should be able to decide for themselves.
“We strongly endorse more widespread over-the-counter access to a preventive agent that can not only prevent cancers but also demonstrably save the lives of tens of thousands of women,” the editorialists said.
“Women contend with much adverse publicity about the risks of oral contraceptives, which surely influences their decision about whether to take these agents,” they said. “Very little is said in the press about the health benefits. [This] paper … helps to redress that balance.”
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