Web site: June 2000
Medsafe Editorial Team
A New Zealand study by Professor David Skegg, and colleagues at the University of Otago looking at deaths from pulmonary embolism in women taking oral contraceptives has now been published in The Lancet (17 June 2000).
The case-control study covered the period from January 1990 to August 1998 and included as cases women aged 15-49 years who had died of confirmed pulmonary embolism. 26 eligible cases were identified from mortality statistics and 17 of these were taking oral contraceptives. Twelve of these women were using an oral contraceptive containing desogestrel or gestodene (third generation), 3 were using an oral contraceptive containing levonorgestrel (second generation) and 2 were using Diane-35, which contains cyproterone acetate and ethinyloestradiol.
Three additional necropsy-confirmed cases of death from pulmonary embolism in users of third generation oral contraceptives have been submitted to the Centre for Adverse Reactions Monitoring during the 10-year period 1990-1999. This makes the total number of cases of fatal pulmonary embolism in New Zealand women taking oral contraceptives during this period at least 20, or 2 women per year. Using national distribution data the absolute risk of death from pulmonary embolism in users of oral contraceptives was estimated by the study authors to be 10.5 per million woman-years. This rate of death is higher than a previous estimate by Medsafe which was 1 death every 18-24 months based on a case fatality rate of 1% from venous thromboembolism (VTE).
Recently published evidence estimates that 3% of those who develop VTE die as a result. These figures suggest that there are 70 cases of VTE in users of oral contraceptives in New Zealand each year. Some of these women may suffer long term consequences as a result of the event.
Odds ratios calculated in the study found third generation oral contraceptives to be associated with 3-times the risk of death from pulmonary embolism compared with second generation pills, but because of the small case numbers the confidence intervals were wide and the difference in risk was not significant. The difference in risk cannot be explained by the percentage use of third generation pills compared with that of second generation pills. The odds ratio for Diane-35 was similar to that for the third generation pills, but the same limitations apply to this estimate.
Medical practitioners and midwives are advised to consider the following recommendations when prescribing low dose oral contraceptives.
The view of the Medicines Adverse Reactions Committee and the Ministry of Health remains unchanged that combined oral contraceptives containing desogestrel or gestodene:
|Historical||family history of VTE
personal history of VTE*
|Acquired predisposition||extensive varicose veins
obesity (body mass index of 30 kg/m² or greater)
*Contraindications for combined oral contraceptives.