Venous thromboembolism: slightly increased risk for women taking oral contraceptives

Clinical bottom line (level 2a)

  1. Women on the oral contraceptive pill were at slightly increased risk of venous thromboembolism (NNF = 6000 for unknown)
  2. There is no clear evidence to suggest that women on HRT are at increased risk of venous thromboembolism
Doukatis et al: Arch Intern Med 1997; 157: 1522-1530
Expires September 2003

The study

Systematic review of studies of case-control, cohort or RCT design of
  • Patients: taking the oral contraceptive pill or hormone replacement therapy
  • Outcome: venous thromboembolism


    • Articles found in ?English using MedLine, 1966 to Oct 1997 (search terms: oral contraceptives, conjugated estrogens and thrombophlebitis )

    Selection criteria: primarily assessing relationship between OCP/HRT and VTE, with over 1000 women/years of follow-up in cohorts
    Appraisal criteria: assessed on four points: baseline matching, standardised ascertainment of exposures, good diagnostic criteria for VTE and high-probability populations for VTE cases
    Articles excluded if: those which included VTE as a risk factor, or compared HRT against OCP

    20 studies with oral contraceptive use, 8 with HRT use
    No significant heterogeneity found

    The evidence

    Patient expected event rate for VTE on HRT: 0.015%
    risk factor for
    VTE on HRT     		adjusted OR
    (95% CI)    		 NNH
    (95% CI)
    case-control (n=5) 2.4
    (1.7 to 3.5)     		6000
    (3400 to 12000)
    prospective cohort 1.7
    (1.0 to 2.9)     		1200
    (4400 to -)
    RCT (n=2) 0.7
    (0.3 to 1.6)     		-2800
    (-14000 to 12000)

    Patient expected event rate for VTE with OCP use: 0.015%
    risk factor for
    VTE with OCP use     		adjusted OR
    (95% CI)    		 NNH
    (95% CI)
    case-control studies (n=12) 3.0
    (2.6 to 3.4)     		4200
    (3500 to 5300)
    retrospective cohorts (n=3) 4.8
    (2.5 to 7.7)     		2200
    (1300 to 5600)
    prospective cohort (n=4) 2.4
    (1.6 to 3.5)     		6000
    (3400 to 14000)
    RCT (n=1) 1.1
    (0.4 to 2.9)     		84000
    (-14000 to 4400)

    Comments

    1. Methodological limitations in studies probably exaggerate the risk. Currently no clear evidence available
    2. Authors suggest
      • patients with a history of venous thromboembolism or thrombophilia should avoid oral contraceptives
      • patients with a history of venous thromboembolism within 2 years or thrombophilia should avoid HRT

    Citation

    1. Doukatis JD, Ginsberg JS, Holbrook A, et al: A re-evaulation of the risk of venous thromboembolism with the use of oral contraceptives or hormone replacement therapy. Arch Intern Med 1997; 157: 1522-1530
    Contributor: Chris Ball and Bob Phillips, February 1998
    Reviewer: Daniel Sontheimer

    Clinical Question.
    Patient women
    Intervention or Exposure taking HRT or OCP
    Outcome venous thromboembolic event; DVT; PE