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  • Title: [Progestins and arterial disease].
    Author: Rozenbaum H.
    Journal: Contracept Fertil Sex (Paris); 1985 Jan; 13(1 Suppl):344-52. PubMed ID: 12280205.
    Abstract:
    The role of estrogens in the etiology of vascular accidents was identified soon after oral contraceptives (OCs) came into use over 2 decades ago, but the role of progestins was only identified on the basis of systematic study. Reduction in the estrogen dose of OCs was accompained by a steady decline in venous accidents, but the rate of arterial accidents changed little. It is important to remember that the actual occurrence of vascular accidents in OC users is rare. Available statistics indicate that age and smoking are important risk factors for vascular accidents. Among nonsmokers and smokers respectively, the annual risk of death due to vascular accidents is 1 in 77,000 and 1 in 10,000 for women under 35, 1 in 67,000 and 1 in 2000 for women 35-44, and 1 in 2500 and 1 in 500 for women 45 and over. Some isolated cases of arterial vascular accidents in users of progestin only OCs have been published. The death rate from vascular accidents is 3 times as high when the levonorgestrel dose increases from 150 to 250 mcg, and twice as high when the norethisterone acetate dose increases from 1 to 4 mg. It is not known precisely how synthetic progestins can induce an arterial accident, but the factors involved may include elevation of blood pressure by potentiation of the modifications in renin-angiotensin system caused by ethinyl estradiol, reducing the level of high density lipoprotein (HDL) cholesterol, impairing glucose tolerance, altering the vascular walls directly, or modifying certain coagulation factors. Little data is available on progestin-caused modifications in coagulation factors, but a recent study reported that the effects of combined OCs on coagulation factors increased with the progestin dose. 2 groups of 19-norsteroids are currently used in contraception, the estranes including norethisterone and some prohormones that metabolize to norethisterone before becoming active, and the gonanes including norgestrel, levonorgestrel, and desogestrel. Early optimism concerning a reduced metabolic impact of desogestrel has given way to controversy. The possible unfavorable metabolic effects of progestins are related to their androgenic properties. Observed effects depend on dose level as well as the hormonal balance of the formulation. Pills with an androgenic climate lower the rate of HDL cholesterol while those with an estrogenic climate raise the HDL cholesterol level, which is preferable if it does not entail a simultaneous increase of VLDL or a modification of coagulation factors.
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