Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23 257 women with ovarian cancer and 87 303 controls

Abstract

SummaryBackground Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health eff ects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these eff ects.Methods Individual data for 23 257 women with ovarian cancer (cases) and 87 303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy.Findings Overall 7308 (31%) cases and 32 717 (37%) controls had ever used oral contraceptives, for average durations among users of 4·4 and 5·0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased but became somewhat attenuated over time-the proportional risk reductions per 5 years of use were 29% (95% CI 23-34%) for use that had ceased less than 10 years previously, 19% (14-24%) for use that had ceased 10-19 years previously, and 15% (9-21%) for use that had ceased 20-29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little aff ected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between diff erent histological types. In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1·2 to 0·8 per 100 users and mortality from 0·7 to 0·5 per 100; for every 5000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented.Interpretation Use of oral contraceptives confers long-term protection against ovarian cancer. These fi ndings suggest that oral contraceptives have already prevented some 200 000 ovarian cancers and 100 000 deaths from the disease, and that over the next few decades the number of cancers prevented will rise to at least 30 000 per year.

Oral contraceptives and menopausal hormone therapy: relative and attributable risks of cardiovascular disease, cancer, and other health outcomes

“…However, today’s formulations contain much lower hormone doses than did the original pills. Typical estrogen doses in OCs prescribed in the 1960s, 1970s, and 1980s (and beyond) were ≥100, ~50, and ≤30 μg, respectively (7). Today, about two-thirds of current OC users in the U.S. take pills containing 30-<50 μg of ethinyl estradiol (low-dose OCs), one-third take pills containing 20 μg (very low dose OCs), and 2% take high-dose pills containing 50 μg (3).…”

“…In a 2008 meta-analysis of 45 case-control and cohort studies, the proportional risk reductions in ovarian cancer incidence per 5 years of OC use were 29% (23-34%), 19% (14-24%), and 15% (9-21%) for use that had stopped <10, 10-19, and 20-29 years prior (7). Despite falling OC estrogen doses during the 1960s, 1970s, and 1980s, the strength of the risk reductions did not vary across calendar time.…”

Menstrual Disorders in Adolescents: Review of Current Practice

“…The COCP is an extremely effective form of contraception if taken correctly, and it also has several health benefits, including a reduction in the risk of ovarian [20], endometrial [21] and colorectal cancer [22]. …”

Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence

“…Similarly, in a meta-analysis assessing cancer risk after exposure to sex hormones [4], no risk increase for ovarian cancer was found after use of COCs. Previous studies have actually shown a decreased risk of ovarian cancer after use of oral contraceptives [15]. For cervical cancer, a small risk increase was shown for present users.…”