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  • Title: [Potential advantages of triphasic combined oral contraceptives in the light of recent epidemiological and endocrinometabolic data].
    Author: Gaspard U, Dubois M.
    Journal: Contracept Fertil Sex (Paris); 1982 Sep; 10(9):551-60. PubMed ID: 12311606.
    Abstract:
    New epidemiologic data on the vascular risks of oral contraceptives (OCs) were assessed to determine whether the recently introduced low dose triphasic pills offer greater potential safety for OC users than previous formulations. Epidemiologic studies have demonstrated that vascular accidents are less frequent with OCs containing lower doses of both estrogens and progestins. The new triphasic pills have the lowest steroid content of any pills yet developed and less of a progestin climate than low dose monophasic pills. The gradual increases in the progestin dose, from 50 mcg on days 1-6 to 75 mcg on days 7-11 and 125 mcg on days 12-21 and of ethinyl estradiol from 30 mcg on days 1-6 to 40 on days 7-11 and back to 30 on days 12-21 reflect the natural cycle of steroid secretion. The endometrial mucus is better developed than under low dose monophasic pills, permitting better cycle control. Triphasic pills have been shown in all studies to block secretion by the hypothalamus and pituitary of the gonadotropins follicle stimulating hormone and luteinizing hormone, resulting in absence of follicular maturation and of ovulation. Even with the small dose of levonorgestrel, the cervical mucus is rendered inhospitable to capacitation and passage of sperm. The impact on glucose tolerance of low doses of ethinyl estradiol, even after long use, is minimal, but the 19 norsteroids used in most combined pills have a more significant impact. To the directly stimulating effect of progestins on pancreatic insulin secretion is added the development of increased peripheral resistence apparently due to a decrease in the number of insulin receptors in the target tissue. The decrease appears to be dose dependent and proportional to the androgenicity of the progestin. A recent study indicated that triphasic pills caused less of a deterioration in glucose tolerance than standard or low-dose combined OCs or a biphasic formulation. This finding was significant because of the possibility that disturbances in carbohydrate metabolism can favor development of vascular diseases. Triphasic OCs have a slight estrogen dominance, which allows them to maintain favorable levels of high density lipoprotein cholesterol, the fraction believed to provide cardiovascular protection. Similarly, they caused minimal variation on the order of 10-15% in the levels of fibrinogen, factors VII, VIII, and X, plasminogen, and antithrombine III. It has not yet been established with certainty however that changes in the levels of these coagulation factors correspond to changes in actual risk of thromboembolic accidents. Triphasics cause a minimal increase in renin substrate and activity of 12-30% compared to the 30-40% at higher estrogen doses. No significant variation in blood pressure has been observed in triphasic OC users.
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