Published: June 2000

Publications

New Zealand Study of Deaths from Pulmonary Embolism in Women of Child-Bearing Age

Information on this subject has been updated. Read the most recent information.

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.

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MINISTRY OF HEALTH (MEDSAFE) ADVICE ON THE USE OF COMBINED ORAL CONTRACEPTIVES

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:

• do not appear to possess significant additional health benefits (eg. reliability of contraception, reduction in the risk of cardiovascular disease) above the second generation oral contraceptives, other than improvement in tolerability and quality of life in some patients;
• may be prescribed for women who have adverse effects such as breakthrough bleeding or androgenic side effects with other combined oral contraceptives.

When initiating contraceptive therapy the prescriber should:

• take a comprehensive personal and family history to exclude contraindications to the use of combined oral contraceptives. If there is a family history of thromboembolism, screening for thrombophilia should be considered in consultation with a haematologist. Hereditary thrombophilia and personal history of venous thromboembolism are contraindications;
• counsel women about the risks and benefits associated with the use of all forms of contraception;
• consider prescribing a low dose combined oral contraceptive, containing no more than 35mcg ethinyloestradiol and a progestogen other than desogestrel or gestodene, where the woman has no contraindications to the use of a combined low dose oral contraceptive and has indicated that she wishes to take a combined oral contraceptive. Prescribe a pill containing a higher dose of oestrogen only if it is specifically indicated.
• advise women about the symptoms of venous thromboembolism, especially pulmonary embolism, and situations of increased risk.

When reviewing combined oral contraceptive therapy the prescriber should:

• review the personal and family history to identify contraindications for the use of combined oral contraceptives and risk factors for venous thromboembolism as for initiation of therapy;
• counsel about the risks and benefits associated with the use of the contraceptive the woman is currently taking compared to the risks and benefits of other forms of contraception;
• if contraindications to the use of combined low dose oral contraceptives are present, another form of contraception should be agreed upon;
• advise women prescribed a combined oral contraceptive about symptoms of venous thromboembolism, especially pulmonary embolism, and situations of increased risk;

For women taking oral contraceptives containing desogestrel or gestodene:

• in the presence of thromboembolic risk factors the woman should be advised to change to a preparation that does not contain desogestrel or gestodene, or to another contraceptive method, as appropriate;
• offer prescription of other hormonal or non-hormonal contraception if, after counselling, the woman finds the relative risk of venous thromboembolism with combined oral contraceptives containing desogestrel or gestodene unacceptable;
• respect the woman's informed choice if she chooses to continue to take her current contraceptive.

Risk factors for venous thromboembolism (VTE)

Historical	family history of VTE personal history of VTE*
Genetic	hereditary thrombophilia*
Acquired predisposition	extensive varicose veins obesity (body mass index of 30 kg/m² or greater) lupus anticoagulant malignancy
Mechanical	immobility trauma surgery
Physiological	dehydration

*Contraindications for combined oral contraceptives.