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Oral contraceptives and the risk of gallbladder disease: a comparative safety study.

Abstract

BACKGROUND
Recent concerns have been raised about the risk of gallbladder disease associated with the use of drospirenone, a fourth-generation progestin used in oral contraceptives. We conducted a study to determine the magnitude of this risk compared with other formulations of oral contraceptives.
METHODS
We conducted a retrospective cohort study using the IMS LifeLink Health Plan Claims Database. We included women who were using an oral contraceptive containing ethinyl estradiol combined with a progestin during 1997-2009. To be eligible, women had to have been taking the oral contraceptive continuously for at least six months. We computed adjusted rate ratios (RRs) for gallbladder disease using a Cox proportional hazards model. In the primary analysis, gallbladder disease was defined as cholecystectomy; in a secondary analysis, it was defined as hospital admission secondary to gallbladder disease.
RESULTS
We included 2,721,014 women in the cohort, 27,087 of whom underwent surgical or laparoscopic cholecystectomy during the follow-up period. Compared with levonorgestrel, an older second-generation progestin, a small, statistically significant increase in the risk of gallbladder disease was associated with desogestrel (adjusted RR 1.05, 95% confidence interval [CI] 1.01-1.09), drospirenone (adjusted RR 1.20, 95% CI 1.16-1.26) and norethindrone (adjusted RR 1.10, 95% CI 1.06-1.14). No statistically significant increase in risk was associated with the other formulations of oral contraceptive (ethynodiol diacetate, norgestrel and norgestimate).
INTERPRETATION
In a large cohort of women using oral contraceptives, we found a small, statistically significant increase in the risk of gallbladder disease associated with desogestrel, drospirenone and norethindrone compared with levonorgestrel. However, the small effect sizes compounded with the possibility of residual biases in this observational study make it unlikely that these differences are clinically significant.

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  • Authors

    Etminan M, Delaney JA, Bressler B, Brophy JM

    Source

    CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 183:8 2011 May 17 pg 899-904

    MeSH

    Adult
    Androstenes
    Cholecystectomy
    Confidence Intervals
    Contraceptives, Oral, Combined
    Contraceptives, Oral, Hormonal
    Contraceptives, Oral, Synthetic
    Desogestrel
    Ethinyl Estradiol
    Female
    Gallbladder Diseases
    Humans
    Levonorgestrel
    Progestins
    Proportional Hazards Models
    Retrospective Studies
    Risk
    Risk Factors

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21502354