Stroke: oral contraceptives increased the risk of a stroke.

Clinical bottom line (level 3b)

  1. Women were at an increased risk of first-ever stroke if they had ever taken oral contraceptives or smoked, though the NNF~6000.
  2. Women were at a further increase in risk of first-ever stroke if they: had ever used oral contraceptives and smoked, or taken oral contraceptives with a high or intermediate progestogen or oestrogen content.
  3. Women were at an increased risk of a fatal event if they if they had ever used oral contraceptives.
Hannaford et al: Stroke 1994; 25: 935-942
Expires November 2003

The study

Case-control study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: community-based from 1400 general practitioners, UK, between 1968 and 1990

1012 patients (aged range 21 to 70 years; median 45, 100% female) women who had a first-ever stroke or an episode of amaurosis fugax

Excluded if
  • history of cerebrovascular disease before recruitment
  • malignancy before the stroke
  • diagnosis of hypertensive encephalopathy
  • vertebrobasilar insufficiency
  • drop attack


    • Cases: 253 patients (% female, mean age ): first-ever stroke or episode of amaurosis fugax
    Controls: 759 patients (% female, mean age ): no diagnosis of stroke or amaurosis fugax

    Factors studied:
  • stroke


    • Factors summarised:
  • ever used oral contraceptives
  • current user of oral contraceptives
  • smokes 1-14 cigarettes daily
  • smokes > or =15 cigarettes daily
  • smokes and current user of oral contraceptives
  • smokes and former user of oral contraceptives
  • oral contraceptives with high progestogen content norethindrone acetate 4 mg + 50 µ g ethinyl oestradiol
  • uses oral contraceptives with intermediate progestogen content 3 mg norethindrone acetate
  • oral contraceptives with high oestrogen content mestranol or ethinyl oestradiol >50 µ g
  • oral contraceptives with intermediate oestrogen content mestranol or ethinyl oestradiol 50 µ g
  • ever used oral contraceptives
  • former user of oral contraceptives
  • smokes and currently using oral contraceptives
  • smokes and former user of oral contraceptives


    • Multiple regression analysis was performed to adjust for confounding factors.

    Outcomes studied:
  • first-ever stroke
  • fatal events (died within 6 months of their first stoke without evidence of alternative cause)

    • The evidence

    Patient expected event rate for first-ever stroke: 0.01%
    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    ever used oral contraceptives 169 84 1.50
    (1.10 to 2.00)     		20003
    (10002 to 100011)
    no ever used oral contraceptives 146 22601

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    current user of oral contraceptives 49 204 2.50
    (1.50 to 4.00)     		6668
    (3335 to 20003)
    no current user of oral contraceptives 266 22481

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    smokes 1-14 cigarettes daily 84 169 2.10
    (1.50 to 2.90)     		9093
    (5265 to 20003)
    no smokes 1-14 cigarettes daily 231 22516

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    smokes > or =15 cigarettes daily 74 179 2.50
    (1.70 to 3.70)     		6668
    (3705 to 14288)
    no smokes > or =15 cigarettes daily 241 22506

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    smokes and current user of oral contraceptives 28 225 2.90
    (1.50 to 5.70)     		5265
    (2129 to 20003)
    no smokes and current user of oral contraceptives 287 22460

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    smokes and former user of oral contraceptives 87 166 1.80
    (1.10 to 2.80)     		12502
    (5557 to 100011)
    no smokes and former user of oral contraceptives 228 22519

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    oral contraceptives with high progestogen content 5 248 6.70
    (1.60 to 28.5)     		1756
    (365 to 16669)
    no oral contraceptives with high progestogen content 310 22437

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    uses oral contraceptives with intermediate progestogen content 14 239 3.60
    (1.60 to 8.20)     		3848
    (1390 to 16669)
    no uses oral contraceptives with intermediate progestogen content 301 22446

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    oral contraceptives with high oestrogen content 6 247 5.80
    (1.50 to 22.8)     		2085
    (460 to 20003)
    no oral contraceptives with high oestrogen content 309 22438

    risk factor first-ever stroke
    present    		 first-ever stroke
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    oral contraceptives with intermediate oestrogen content 40 213 2.90
    (1.70 to 5.00)     		5265
    (2501 to 14288)
    no oral contraceptives with intermediate oestrogen content 275 22472

    risk factor fatal events
    present    		 fatal events
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (% CI)
    ever used oral contraceptives 51 202 2.30
    (1.20 to 4.40)
    no ever used oral contraceptives 51 202

    risk factor fatal events
    present    		 fatal events
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (% CI)
    former user of oral contraceptives 41 212 2.40
    (1.20 to 4.70)
    no former user of oral contraceptives 41 212

    risk factor fatal events
    present    		 fatal events
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (% CI)
    smokes and currently using oral contraceptives 9 244 7.10
    (1.50 to 33.0)
    no smokes and currently using oral contraceptives 9 244

    risk factor fatal events
    present    		 fatal events
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (% CI)
    smokes and former user of oral contraceptives 32 121 5.00
    (1.80 to 14.0)
    no smokes and former user of oral contraceptives 32 121

    Comments

    1. No duration of time since pill was stopped was indicated or whether the time since stopping is a factor.

    Citation

    1. Hannaford PC, Croft PR, Kay CR, et al: Oral contraceptives and stroke: Evidence from the Royal College of General Practitioners' Oral Contraception Study. Stroke 1994; 25: 935-942
    Search Terms: stroke in Best Evidence
    Contributor: Nick Shenker and Clare Wotton, November 1999
    Reviewer: Sylvie Antonini-Revaz

    Clinical Question.
    Patient women with first-ever stroke or amaurosis fugax
    Intervention or Exposure oral contraceptive use
    Comparison no oral contraceptive use
    Outcome stroke