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Research

Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis

Steven T. Bird, Abraham G. Hartzema, James M. Brophy, Mahyar Etminan and Joseph A.C. Delaney
CMAJ February 05, 2013 185 (2) E115-E120; DOI: https://doi.org/10.1503/cmaj.120677
Steven T. Bird
Department of Health and Human Services (Bird), Food and Drug Administration, Center for Drug Evaluation and Research, Office of Management and Academic Collaboration Program; Department of Pharmaceutical Outcome and Policy (Bird, Delaney, Hartzema), University of Florida College of Pharmacy, Gainesville, Fla.; Department of Medicine and Epidemiology (Brophy), McGill University, Montréal, Que.; and the Pharmaceutical Outcomes Programme (Etminan), School of Medicine, University of British Columbia, Vancouver, BC
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  • For correspondence: bird.steven@gmail.com
Abraham G. Hartzema
Department of Health and Human Services (Bird), Food and Drug Administration, Center for Drug Evaluation and Research, Office of Management and Academic Collaboration Program; Department of Pharmaceutical Outcome and Policy (Bird, Delaney, Hartzema), University of Florida College of Pharmacy, Gainesville, Fla.; Department of Medicine and Epidemiology (Brophy), McGill University, Montréal, Que.; and the Pharmaceutical Outcomes Programme (Etminan), School of Medicine, University of British Columbia, Vancouver, BC
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James M. Brophy
Department of Health and Human Services (Bird), Food and Drug Administration, Center for Drug Evaluation and Research, Office of Management and Academic Collaboration Program; Department of Pharmaceutical Outcome and Policy (Bird, Delaney, Hartzema), University of Florida College of Pharmacy, Gainesville, Fla.; Department of Medicine and Epidemiology (Brophy), McGill University, Montréal, Que.; and the Pharmaceutical Outcomes Programme (Etminan), School of Medicine, University of British Columbia, Vancouver, BC
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Mahyar Etminan
Department of Health and Human Services (Bird), Food and Drug Administration, Center for Drug Evaluation and Research, Office of Management and Academic Collaboration Program; Department of Pharmaceutical Outcome and Policy (Bird, Delaney, Hartzema), University of Florida College of Pharmacy, Gainesville, Fla.; Department of Medicine and Epidemiology (Brophy), McGill University, Montréal, Que.; and the Pharmaceutical Outcomes Programme (Etminan), School of Medicine, University of British Columbia, Vancouver, BC
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Joseph A.C. Delaney
Department of Health and Human Services (Bird), Food and Drug Administration, Center for Drug Evaluation and Research, Office of Management and Academic Collaboration Program; Department of Pharmaceutical Outcome and Policy (Bird, Delaney, Hartzema), University of Florida College of Pharmacy, Gainesville, Fla.; Department of Medicine and Epidemiology (Brophy), McGill University, Montréal, Que.; and the Pharmaceutical Outcomes Programme (Etminan), School of Medicine, University of British Columbia, Vancouver, BC
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Article Figures & Tables

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    Table 1:

    Health care and combined oral contraceptive use at baseline

    CharacteristicPolycystic ovary syndrome*Matched controls
    Women, no.43 50643 506
    Age, yr, mean28.728.9
    Health care use, % of women
    Admission to hospital3.574.05
    Emergency department visit4.794.45
    Physician office visit51.3150.08
    Combined oral contraceptive use
    New user,† no. (%) of women20 150 (46.32)20 278 (46.61)
    Prevalent user,‡ no. (%) of women23 356 (53.68)23 228 (53.39)
    Prior time on combined oral contraceptives, mean, d103103
    Total time on combined oral contraceptives, mean, d201202
    Number of combined oral contraceptives products used in the past, mean0.60.6
    Combined oral contraceptive, % of women
    Desogestrel, μg ethinyl estradiol
     203.453.38
     250.470.46
     308.398.31
    Drospirenone, μg ethinyl estradiol
     207.468.45
     3020.8121.02
    Levonorgestrel, μg ethinyl estradiol
     205.195.14
     303.753.72
     Triphasic2.352.11
    Norethindrone, μg ethinyl estradiol
     3510.5310.28
    Norethindrone acetate, μg ethinyl estradiol
     204.604.48
     302.742.66
     351.511.55
    Norgestimate, ethinyl-estradiol μg
     255.785.68
     3518.3118.21
    Norgestrel, μg ethinyl estradiol
     304.664.55
    • ↵* Defined as a claim for polycystic ovary syndrome (International Classification of Disease, 9th Revision [Clinical Modification (ICD-9-CM)] 256.4).

    • ↵† Initiated combined oral contraceptive therapy after the polycystic ovary syndrome claim.

    • ↵‡ Evidence of combined oral contraceptive use during the 365-day period before the polycystic ovary syndrome claim.

    • View popup
    Table 2:

    Comparison of medication use and comorbidities at cohort entry and study end

    VariableCohort entryStudy end
    PCOS*Matched controlsPCOS*Matched controls
    Medication use, % of women
    ACE inhibitor or ARB2.182.575.065.10
    Beta blocker3.423.527.956.80
    Benzodiazepine8.938.0620.7716.95
    Calcium-channel blocker0.921.062.512.18
    Diabetes medications20.3120.6542.8821.55
    SSRI or tricyclic antidepressant17.0917.3231.7628.88
    Statin or fibrate2.452.795.795.23
    Comorbidities, % of women
    Acne11.0410.9224.1519.65
    Asthma6.936.9215.3212.82
    COPD3.343.4511.459.29
    Diabetes6.708.3114.8712.23
    Dysmenorrhea5.795.7114.2310.95
    Endometriosis2.712.827.424.88
    Hyperlipidemia10.4710.9127.1020.15
    Hypertension7.828.4018.7014.75
    Hypothyroid8.238.3217.2312.67
    Ovarian inflammation1.741.835.723.84
    Vaginal inflammation12.5612.5231.2227.64
    Uterine leiomyoma2.052.035.964.65
    Irregular menstrual cycle40.0440.0672.0754.15
    Migraine5.535.6715.1012.33
    Mood or anxiety disorder15.9616.2634.0929.65
    Obesity13.3513.3233.1121.04
    Peptic ulcer disease0.400.421.321.03
    Premenstrual tension syndrome (PMS or PMDD)1.421.344.122.97
    Sleep disorder0.820.883.261.98
    Smoking2.572.717.316.85
    • Note: ACE = angiotensin-converting enzyme, ARB = angiotensin-receptor blocker, COPD = chronic obstructive pulmonary disorder, PCOS = polycystic ovary syndrome, PMDD = premenstrual dysphoric disorder, PMS = premenstrual syndrome, SSRI = selective serotonin reuptake inhibitor.

    • ↵* Defined as a claim for PCOS (International Classification of Disease, 9th Revision [Clinical Modification (ICD-9-CM)] 256.4).

    • View popup
    Table 3:

    Risk of venous thromboembolism associated with PCOS in women taking the combined oral contraceptive pill

    VariableCox proportional hazards modelsRelative risk regression
    PCOS claim2.14 (1.41–3.24)2.12 (1.40–3.21)
    Composite PCOS definition*2.24 (1.62–3.10)2.23 (1.61–3.08)
    PCOS symptoms and treatment
     Anovulation1.72 (0.75–3.98)1.70 (0.75–3.89)
     Hirsutism2.49 (1.35–4.59)2.43 (1.30–4.56)
     Spironolactone1.89 (1.15–3.10)1.86 (1.14–3.03)
    • Note: PCOS = polycystic ovary syndrome.

    • ↵* Claims for PCOS, anovulation, hirsutism, spironolactone treatment, or PCOS-related procedures.

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Canadian Medical Association Journal: 185 (2)
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Vol. 185, Issue 2
5 Feb 2013
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Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis
Steven T. Bird, Abraham G. Hartzema, James M. Brophy, Mahyar Etminan, Joseph A.C. Delaney
CMAJ Feb 2013, 185 (2) E115-E120; DOI: 10.1503/cmaj.120677

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Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis
Steven T. Bird, Abraham G. Hartzema, James M. Brophy, Mahyar Etminan, Joseph A.C. Delaney
CMAJ Feb 2013, 185 (2) E115-E120; DOI: 10.1503/cmaj.120677
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