HEMORRHAGIC STROKE, OVERALL STROKE RISK, AND COMBINED ORAL-CONTRACEPTIVES - RESULTS OF AN INTERNATIONAL, MULTICENTER, CASE-CONTROL STUDY

Background The risk of haemorrhagic stroke associated with use of oral contraceptives (OCs) is less well-established than that for ischaemic stroke. We assessed the risk of haemorrhagic stroke associated with c urrent use of modern OCs as now used throughout the world. Methods In this WHO collaborative, case-control study, we assessed the associatio n between risk of haemorrhagic stroke and use of combined OCs in 1068 cases, 20-44 years, and 2910 age-matched controls. We also assessed ri sks for all strokes combined (haemorrhagic, ischaemic, and unclassifie d) based on 2198 cases and 6086 controls. Findings Overall, current us e of combined OCs was associated with slightly increased risk of haemo rrhagic stroke; the increase was significant in the developing countri es (odds ratio 1 . 76 [95% CI 1 . 34-2 . 30]) but not in Europe (1 . 3 8 [0 . 84-2 . 25]). Use of OCs in women younger than 35 years did not affect risk of haemorrhagic stroke in either group of countries, where as in women aged older than 35 years, odds ratios were greater than 2. Women who were current users of OCs and had a history of hypertension (detected before current episode of OC use, but not during pregnancy) had a substantially increased risk (ten-fold to 15-fold) of haemorrha gic stroke compared with women who did not use OCs and had no history of hypertension. Odds ratios among current OC users who were also curr ent cigarette smokers were greater than 3. In both groups of countries , past use of OCs, dose of oestrogen, and dose and type of progestagen had no effect on risk, and risks were similar for subarachnoid and in tracerebral haemorrhage. The odds ratios for any type of stroke associ ated with current use of low-dose (<50 mu g oestrogen) and higher-dose OCs were 1 . 41 (0 . 90-2 . 20) and 2 . 71 (1 . 70-4 . 32), respectiv ely, in Europe and 1 . 86 (1 . 49-2 . 33) and 1 . 92 (1 . 48-2 . 50) i n the developing countries. From these data we estimated that about 13 % and 8% of all strokes in women aged 20-44 in Europe and the developi ng countries, respectively, are attributable to the use of OCs. Interp retation The risk of haemorrhagic stroke attributable to OC use is not increased in younger women and is only slightly increased in older wo men. The estimated excess risk of all stroke types associated with use of low-oestrogen and higher-oestrogen dose OCs in Europe was about tw o and eight, respectively, per 100 000 woman-years of OC use. However, findings need to be considered in the context of other risks and bene fits associated with OC use, as well as those associated with the use of other forms of contraception.