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  • Title: Gestodene-containing contraceptives.
    Author: Kuhl H, Jung-Hoffmann C, Wiegratz I.
    Journal: Clin Obstet Gynecol; 1995 Dec; 38(4):829-40. PubMed ID: 8616979.
    Abstract:
    As GSD is the most potent progestogen used in oral contraceptives, the doses of GSD can be lower than those of other progestogen components. The monophasic (30 micrograms EE + 75 micrograms GSD) and the triphasic formulation (30 micrograms EE + 50 micrograms GSD/40 micrograms EE + 70 micrograms GSD/30 micrograms EE + 100 micrograms GSD) suppress gonadotropin release and ovarian function profoundly and inhibit ovulation reliably. The strong anti-estrogenic and progestogenic effectiveness of GSD is based on the high GSD serum concentrations achieved during daily intake. Because of the weak androgenic properties of GSD, both formulations can be characterized as estrogen-dominant with respect to their hepatic effects. Except for the first cycles, both formulations afford good cycle control, and the rate of side effects is similar to that with comparable low-dose oral contraceptives. The levels of total and free androgens and androgen precursors, as well as of peripheral androgen activity, are significantly reduced, resulting in a reduced incidence of acne. The concentrations of SHBG and other serum-binding globulins are elevated considerably, and thyroid function is almost unaffected. The estrogen-dominant effect on hepatic metabolism of both formulations also is reflected by a significant increase in the levels of triglycerides and VLDL, HDL, and some apolipoproteins, while LDL-CH and total CH remain unchanged. Similar to other low-dose oral contraceptives, the GSD-containing preparations cause a slight impairment of glucose tolerance that does not appear to be of clinical relevance. However, a significant increase exists in pro-coagulatory and fibrinolytic activity that leads to a considerable stimulation of fibrin turnover. In predisposed women, this may contribute to an elevated risk of venous and arterial thromboembolic diseases. Gestodene (GSD) is the most potent and therefore lowest dosed progestogen used in oral contraceptives. Pharmacokinetic studies have found serum levels of GSD to be considerably higher than those of comparable progestogens taken at higher doses. The monophasic and triphasic formulation suppress gonadotropin release and ovarian function profoundly and inhibit ovulation reliably, with GSD's strong anti-estrogenic and progestogenic effectiveness based upon the high GSD serum concentrations achieved during daily intake. The authors describe the pharmacologic properties of GSD, formulations containing GSD and ethinyl estradiol, pharmacokinetics, contraceptive effectiveness, cycle control and side effects, the effect on hormonal parameters, the effect on lipid metabolism, the effect on carbohydrate metabolism, and the effect on hemostasis.
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