The effects of two progestogen-only pills containing either desogestrel (75 μg/day) or levonorgestrel (30 μg/day) on lipid metabolism☆

Abstract

The effects of two progestogen-only pills (POPs) containing either desogestrel (75 μg/day) or levonorgestrel (30 μg/day) on lipid metabolism were compared in a double-blind, randomized study in Sweden and Finland. Eighty-one healthy female volunteers received either desogestrel 75 μg/day or levonorgestrel 30 μg/day for seven treatment periods of 28 days. The following lipid parameters were measured at screening and at treatment Periods 3 and 7: total cholesterol, total triglycerides, HDL-cholesterol, HDL₂-cholesterol, HDL₃-cholesterol, LDL-cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, lipoprotein (a), and the carrier proteins sex hormone-binding globulin (SHBG) and cortisol-binding globulin. Overall, both study medications had similar, minimal effects on lipid metabolism. To summarize, compared with pre-treatment, no changes were observed for LDL-cholesterol and its protein fraction apolipoprotein B. The concentrations of total cholesterol and triglycerides decreased marginally. Decreasing trends were also seen for lipoprotein (a), HDL-cholesterol and its subfractions, HDL₂-cholesterol and HDL₃-cholesterol, and the apolipoproteins, apolipoprotein A-I and apolipoprotein A-II. The results indicated no significant differences between the groups in any of the parameters, with the exception of a smaller decrease in HDL₃-cholesterol at treatment Period 7 for the desogestrel-containing POP compared with the levonorgestrel-containing POP and a significant difference between the two treatments for lipoprotein (a) at Period 3. The serum concentration of the carrier protein SHBG was found to be slightly higher in the desogestrel group, which may be a manifestation of the higher androgenicity of levonorgestrel compared with desogestrel. It can be concluded that the POP containing 75 μg desogestrel has a negligible effect on lipid metabolism. Despite the higher progestogen dose, the effect of this new POP is similar to that of a traditional POP containing 30 μg levonorgestrel.

Introduction

The progestogen-only pill (POP) is a suitable alternative to oral contraceptives containing a combination of estrogen and progestogen. However, because of their lower contraceptive efficacy and unpredictable bleeding pattern, the POPs that have been available until now have generally been less well-accepted than combined oral contraceptives by both prescribers and users. Consequently, the traditional POPs have mainly been reserved for specific groups of women, such as women with contraindications for estrogens.

Etonogestrel, the biologically active metabolite of desogestrel, is a selective progestogen that combines high progestogenic activity with a lower intrinsic androgenicity than those progestogens used in traditional POPs [1], [2]. As a result of its intrinsic low androgenicity, it is anticipated that a higher daily dose of desogestrel would consistently inhibit ovulation, without triggering androgen-related effects on lipid and carbohydrate metabolism and on the skin. Ovarian function has been shown to be dose-relatedly suppressed with daily doses of 30, 50, and 75 μg of desogestrel [3]. Of these doses, the optimal one was found to be 75 μg because it showed the highest extent of ovarian suppression and a more acceptable bleeding pattern than the lower doses. In a double-blind, multicenter study involving over 1000 participants, desogestrel 75 μg/day (Cerazette) was shown to inhibit ovulation in 98% of cycles, and to have a higher contraceptive efficacy and a similar overall acceptability, than levonorgestrel 30 μg/day [4]. The aim of the present study was to compare the effect of desogestrel 75 μg/day and levonorgestrel 30 μg/day on lipid metabolism in healthy female volunteers.