ISCHEMIC STROKE AND COMBINED ORAL-CONTRACEPTIVES - RESULTS OF AN INTERNATIONAL, MULTICENTER, CASE-CONTROL STUDY

Background The association between use of oral contraceptives (OCs) an d cerebral infarction was established in studies from northern Europe and the USA during the 1960s and 1970s. Since then, the constituents o f hormonal OCs have changed and now contain lower doses of oestrogen a nd progestagen. Current recommendations restrict OC use to younger wom en who do not have other risk factors for cardiovascular disease, in t his international study we assessed the risk of CC-associated first st roke in women from Europe and other countries throughout Vie world. Me thods In this hospital-based, case-control study, we assessed the risk of ischaemic stroke in association with current use of combined OCs i n 697 cases, aged 20-44 years, and 1962 age-matched hospital controls in 21 centres in Africa, Asia, Europe, and Latin America. The diagnosi s of ischaemic stroke was almost exclusively based on computed tomogra phy (CT), magnetic resonance imaging (MRI), or cerebral angiography ca rried out within 3 weeks of the clinical event. Ail cases and controls were interviewed while in hospital with the same questionnaire, which included information on medical and personal history, details of life time contraceptive use, and blood-pressure measurements before the mos t recent episode of OC use. Findings The overall odds ratio of ischaem ic stroke was 2 . 99 (95% CI 1 . 65-5 . 40) in Europe and 2 . 93 (2 . 15-4 . 00) in the non-European (developing) countries, Odds ratios wer e lower in younger women and those who did not smoke, and less than 2 in women who did not have hypertension and who reported that their blo od pressure had been checked before the current episode of OC use. By contrast, among current OC users with a history of hypertension, the o dds ratio was 10 . 7 (2 . 04-56 . 6) in Europe and 14 . 5 (5 . 36-39 . 0) in the developing countries. In Europe, the odds ratio associated with current use of low-dose OCs (<50 mu g oestrogen) was 1 . 53 (0 . 71-3 . 31), whereas for higher-dose preparations it was 5 . 30 (2 . 56 -11 . 0). In the developing countries, there was no significant differ ence between overall estimates of risk associated with use of low-dose or higher-dose OCs (3 . 26 [2 . 19-4 . 86] vs 2 . 71 [1 . 75-4 . 19]) , This differential effect of dose in Europe and the developing countr ies is likely to be due to different levels of other risk factors amon g users of low-dose and higher-dose OCs in the two groups of countries . There was no significant increase in odds ratios with increasing dur ation of OC use among current users; odds ratios were not significantl y increased after cessation of OC use. Interpretation The incidence of ischaemic stroke is low in women of reproductive age and any risk att ributable to OC use is small. The risk can be further reduced if users are younger than 35 years, do not smoke, do not have a history of hyp ertension, and have blood pressure measured before the start of QC use . In such women OC preparations with low oestrogen doses may be associ ated with even lower risk.