This review details the characteristic features of three new progestogens which soon will be available in low-dose combination oral contraceptive agents in the United States. Available data suggest that desogestrel, gestodene, and norgestimate are extremely potent progestogens with few androgenic side effects. The smaller changes in lipids induced by these progestogens seem to confer some advantage to the use of preparations containing one of these agents. Whether this advantage is also present clinically remains to be determined.
PIP: 3 about-to-be marketed progestogens (desogestrel, gestodene, and norgestimate) are discussed in terms of their structural characteristics and metabolism, biological activity, effects on carbohydrate and lipid metabolism, and effects on coagulation. There appears to be little difference in clinical efficacy between the new progestogens and those currently available in the US. What difference, there is to be that the androgenic metabolic effects are minimized with the new progestogens. It is though that a comparison of the clinical benefits of these agents would be difficult. Synthetic progestogens are used in oral contraceptives (OC) in order to inhibit ovulation. In combination with estrogen, they can have antiestrogenic properties. Steroid dose and potency in OCs is noted as an important consideration in comparing progestogens. The new progestogens, like the US-marketed DL-norgestrel and levonorgestrel, are gonanes, which like estranes are structured with the absence of a methyl group between rings A and B and the presence of an ethinyl group in position 17 alpha. Each is different metabolically. Studies of the biological activity of these new progestogens are difficult to compare because of labeling, dose, experimental methods, measurement errors, and the inclusion of the estrogen component, which is known to be contributory to the side effects. Only potency can be compared and gestodene has the strongest effect on inhibiting ovulation an transforming the endometrium into secretory endometrium. All have little estrogenic effects an are weak antiestrogens, with little androgenic activity as measured by the increase in seminal vesicle or prostatic weight of laboratory animals. Circulatory bonding is found in various forms. Although not clinically demonstrated, it is possible that gestodene, which is a competitive inhibitor to aldosterone, may be useful to those with hypertension. Because of the marked increase in circulating concentrations of SHBG of gestodene and desogestrel, it may be useful to those with hirsutism upon additional clinical testing. The selected review of studies on the effects of the new progestogens on carbohydrate and lipid metabolism, including the HDL and LDL cholesterol levels, suggests small effects of questionable clinical significance. Based on clinical trials of gestodene in Europe, there appears to be no greater incidence of thromboembolic activity or effects on coagulation an fibrinolysis than previously reported.