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  • Title: Progestogens and arterial disease--evidence from the Royal College of General Practitioners' study.
    Author: Kay CR.
    Journal: Am J Obstet Gynecol; 1982 Mar 15; 142(6 Pt 2):762-5. PubMed ID: 6801981.
    Abstract:
    In the course of a large-scale prospective study of the health of oral contraceptive users, the rate of reporting of arterial diseases was examined in two groups of users of pill brands that permitted the effect of the progestogen to be assessed independently of estrogen effect. The rate of reporting was consistently higher with the brands with the higher progestogenic activity. The reports of cerebrovascular diseases showed a significant trend in relation to the dose of norethindrone acetate as well as in relation to total arterial diseases. Total arterial diseases were also reported more frequently in association with brands containing 250 microgram of levonorgestrel than with those containing 150 microgram of this progestogen. The mean serum levels of high-density lipoprotein cholesterol in users of the brands described show a striking inverse relationship to the rate of reporting of arterial diseases and to the progestogenic activity of the pills. A large-scale prospective study of 23,000 current oral contraceptive users and a similar number of matched nonusers (controls) was conducted to evaluate the effects of 2 types of progestogens (norethindrone acetate of NEA and levonorgestrel) on the rate of reporting of arterial diseases. 3 NEA pills contained 50 mcg of ethinyl estradiol combined with 1, 3, and 4 mg of NEA. 2 levonorgestrel pills contained 30 mcg ethinyl estradiol combined with 150 and 250 mcg respectively of levonorgestrel. All 3 categories of arterial diseases (ischemic heart disease, cerebrovascular, and peripheral vascular diseases) exhibited a clear association of higher rates of reporting with larger doses of progestogens. In cerebrovascular diseases specifically, and arterial diseases in general, the trend with the NEA dose is statistically significant (P0.05). Pills with 250 mcg levonorgestrel are also significantly associated with a higher rate of total arterial disease than those with 150 mcg of progestogen. A striking inverse relationship is observed between high density lipoprotein cholesterol and the progestogen dose and rate of reporting of arterial disease, confirming previous observations. This study does not provide evidence that progestogens administered alone would have the same effects, nor does it assume that estrogens do not contribute to the increased risk of vascular disease in pill users. The need to develop a contraceptive risk of vascular disease in pill users. The need to develop a contraceptive pill with the lowest activity of both steroids consistent with contraceptive effectiveness and high menstrual cycle control is indicated.
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