By 31 December 1993 the cohort had been followed for 25 years and the median age of the women was 49 years (48 for ever users of oral contraception and 50 for never users). During that period 1599 deaths were reported, 945 in ever users and 654 in never users (table ). The death rate from all causes combined was 21% lower than in the UK population (overall standardised mortality ratio=79). The relative risk of death from all causes combined after adjustment for age, parity, social class, and cigarette smoking did not differ significantly between ever users and never users (relative risk=1.0, 95% confidence interval 0.9 to 1.1; P=0.7).
Standardised mortality ratios in ever users and never users of oral contraceptives and relative risk in ever users compared with never users
Table also shows standardised mortality ratios and adjusted relative risks of death for common specific causes and groups of causes of death (and also for some particular causes that have been reported to be affected by oral contraceptive use) according to ever use of oral contraceptives. For most specific causes of death the standardised mortality ratios in ever users and never users of oral contraceptives were around 100 and did not differ significantly between the two groups. The few exceptions were colorectal cancer and ovarian cancer, for which the relative risks of death in users were significantly below 1.0, and cerebrovascular disease and all violent and accidental causes of death, for which the relative risks were significantly greater than 1.0. Ever use is, however, a crude measure of use of oral contraceptives.
Table shows for various causes the relative risk of death compared with never users in relation to the number of years since oral contraceptives were first used. Within the first 10 years of starting use of oral contraceptives there was a significant excess mortality from all causes of death (relative risk=1.2, 95% confidence interval 1.0 to 1.50; P=0.03), all circulatory diseases (2.2, 1.5 to 3.2; P<0.0001), and cerebrovascular disease (2.7, 1.5 to 4.9; P=0.0008). However, the excess mortality from these causes fell with time, this trend being significant for all circulatory disease (P=0.002) and cerebrovascular disease (P=0.02). There were 380 deaths in women who began using oral contraceptives more than 20 years before the end of follow up, and this group showed no significant excess or deficit in mortality from any specific condition or overall.
Relative risk of death in users of oral contraceptives compared with never users according to time since first use
Table shows the pattern of risk of death for various conditions in relation to the time since stopping use of oral contraceptives. By the end of follow up the median time since last use in the cohort was 17 years. Significant increases or decreases in risk were found mainly in current users or those who had stopped use within the past 10 years—for example, women who were current users or who stopped use in the past five years had a significantly reduced risk of ovarian cancer (0.1, 0.0 to 0.9; P=0.04) and a significant excess of all circulatory diseases (1.7, 1.2 to 2.4; P=0.006) and cerebrovascular disease (1.9, 1.1 to 3.4; P=0.03) and women who had stopped use five to nine years previously had an significant excess risk of cervical cancer (3.0, 1.1 to 8.1; P=0.03) and cerebrovascular disease (2.0, 1.1 to 3.7; P=0.02). Among women who had stopped use 15 or more years previously most of the relative risks were around 1.0. For ovarian cancer there was a weak suggestion that the protective effect associated with current or recent use wore off (test for trend, P=0.05).
Relative risk of death in users of oral contraceptives compared with never users according to time since last use
Among ever users of oral contraceptives, the average duration of use was five years. Table shows the relative risk of death in relation to the duration of use of oral contraceptives. Women who used oral contraceptives for 10 or more years had a significant excess mortality from lung cancer (2.0, 1.1 to 3.5; P=0.02) and cervical cancer (4.1, 1.6 to 10.6; P=0.003). The excess deaths from lung cancer were mainly among smokers (17 deaths in smokers and three in non-smokers), the relative risk associated with 10 or more years of use of oral contraceptives being 2.0 for smokers and 2.2 for non-smokers. This excess may be a chance finding or perhaps due to residual confounding. There was also a significant trend of increasing mortality for all cancers combined and for cervical cancer in relation to duration of use (P=0.02 and 0.03, respectively).
Relative risk of death in users of oral contraceptives compared with never users according to duration of use
Duration of use and time since first and last use of oral contraceptives were highly correlated, with current and recent users being more likely to have used contraceptives for longer. Table shows the relative risk of death among ever users of oral contraceptives according to time since last use of oral contraceptives and duration of use. All significant results were confined to women currently using oral contraceptives or who had stopped in the past 10 years, although among such women duration of use was not associated with a significant increase or decrease in mortality from any particular cause or overall. Women who stopped using oral contraceptives 10 or more years previously had no significant increases or decreases in relative risk of death from any cause, even if they had used them for 10 years or more. There were, however, only 54 deaths in this subgroup.
Relative risk† of death in users of oral contraceptives compared with never users according to time since last use and duration of use