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  • Title: [Third generation progestagens].
    Author: Belaisch J, Eliakim V.
    Journal: Contracept Fertil Sex (Paris); 1993 Apr; 21(4):287-93. PubMed ID: 12318226.
    Abstract:
    Desogestrel, gestodene, and norgestimate, the third-generation 19-nortestosterone derivatives, have allowed the steroid doses in combined oral contraceptives (OCs) to be reduced. Gestodene has the strongest antigonadotropic action of the three, which allows the dose level to be reduced and the androgenic effects to be reduced automatically. Gestodene is the strongest synthetic progestin in terms of inhibiting ovulation. The antigonadotropic activity is correlated with an excellent progestational activity. Norgestimate offers a reduced androgenic activity without greater antigonadotropic potency. Desogestrel is both more strongly antigonadotropic and less androgenic than previous generations of synthetic progestins. Since the major disadvantage of OCs according to most authors is the increased risk of vascular accidents, the potential contribution of the new progestins in reducing vascular risks is of great importance. No epidemiologic studies have yet confirmed in a statistically significant way that pills containing the new progestins cause fewer vascular accidents compared to earlier formulations. It is possible only to draw conclusions from the indirect evidence of studies already performed. Analysis of data from the Royal College of General practitioners has indicated that the androgenic effect of progestins, reflected in reduction of HDL cholesterol, is a factor in occurrence of arterial accidents. Research on women using OCs containing the new progestins indicates that they have little or no deleterious effect on lipid or carbohydrate metabolism. A beneficial effect of the third-generation progestins on the coagulation factors is less apparent. It has been suggested that with a reduced androgenic effect of the progestins, the activity of ethinyl estradiol is more perceptible, since estrogens are the source of disturbance in coagulation factors. Comparisons of pills containing gestodene and levonorgestrel and a triphasic levonorgestrel formulation with a monophasic desogestrel pill have found few significant differences. The third generation of progestins does not appear to represent as important an advance in reducing arterial accidents as the reduction from 50 to 30 mcg of ethinyl estradiol did in reducing venous pathology. There is as yet no data on the possible effect of either the formulations containing 30 mcg of ethinyl estradiol or the third generation of progestins on the likelihood of developing breast cancer. Clinical tolerance and cycle control have been very good with the new progestins. The third-generation norpregnane derivatives have a progestational action with almost no androgenic effect, which gives them excellent metabolic tolerance. Pills containing norpregnane derivatives only can be used in women with thrombotic risk factors, but their longterm effects on the breast cannot be predicted and they cause cycle disturbances in a significant proportion of users.
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