Elsevier

Contraception

Volume 65, Issue 3, March 2002, Pages 223-229
Contraception

Original research article
Effect of dienogest-containing oral contraceptives on lipid metabolism

https://doi.org/10.1016/S0010-7824(01)00310-9Get rights and content

Abstract

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on lipid metabolism was investigated. Four groups composed of 25 volunteers each (mean age 26.1 ± 4.5 years; body mass index 21.9 ± 2.8 kg/m2) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 μg ethinyl estradiol (EE) + 2 mg dienogest (DNG) (30 EE/DNG), 20 μg EE + 2 mg DNG (20 EE/DNG), 10 μg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG), or 20 μg EE + 100 μg levonorgestrel (LNG; EE/LNG). The study was completed by 91 women. Blood samples were taken by venipuncture after at least 12 h fasting on Days 21–26 of the control cycle and Days 18–21 of the first, third, and sixth treatment cycle.

There were clear differences between the effects of EE/LNG and the formulations containing estrogens and DNG. Although EE/LNG did not change the triglycerides levels, a significant increase was observed during treatment with the DNG-containing preparations. Although EE/LNG significantly reduced HDL-CH and HDL2-CH, there was a nonsignificant increase with the DNG-containing OCs. No change was observed in the levels of HDL3-CH. A significant rise in apolipoprotein A1 occurred during intake with the three DNG-containing formulations, but not with EE/LNG. In contrast to the women treated with combinations of estrogens and DNG, apolipoprotein B rose significantly in the women in the EE/LNG group. Lipoprotein (a) was significantly reduced by 30 EE/DNG and EE/LNG and remained unaltered with 20 EE/DNG and EE/EV/DNG. Altogether, the changes in lipid metabolism caused by the DNG-containing formulations appeared to be more favorable than those observed with EE/LNG. In OCs with DNG, the EE dose does not seem to play a major role with respect to the effect on lipids.

Introduction

The 40-year history of oral contraceptives (OCs) can be characterized as a perpetual attempt to minimize the well-known health risks of this commonly used method. Since the first reports on venous thromboembolic diseases occurring during the intake of OCs, which have been assumed to be caused primarily by the synthetic estrogen component, the efforts for further development of OCs were focussed on the dose reduction of ethinyl estradiol (EE). The idea of using the natural estradiol instead of EE in OCs failed because of the poor cycle control. Another aspect was the assumption that a progestogen component with androgenic properties may cause deleterious effects with respect to the risk of arterial diseases [1]. Consequently, new progestogens that show only weak or no androgenic actions were developed.

The main problem of developing OCs is that the efficacy and risk profile of a new formulation can only be judged on the basis of epidemiologic data, which, however, are available late, i.e., when millions of women have used the preparation for a sufficient duration of time. As a way out of this dilemma, metabolic surrogate parameters that are regarded to reflect possible risk potentials have been chosen. Therefore, the measurement of, e.g., hemostasis parameters, lipids and lipoproteins, or parameters of carbohydrate metabolism, has become mandatory, even though the interpretation of the results with respect to the health risk is questionable.

In search of new preparations that may fulfill the criteria of low-risk OCs, very low doses of EE or even estradiol as the estrogen component were combined with dienogest (DNG), which is a progestogen with no androgenic but with antiandrogenic properties. In the present study, the effect on lipid metabolism of monophasic combinations of 2 mg DNG with either 30 μg or 20 μg EE or 10 μg EE plus 2 mg estradiol valerate (EV) were compared with that of an OC containing 20 μg EE and 100 μg levonorgestrel (LNG).

Section snippets

Design of the study

One-hundred healthy women between 18 years and 35 years of age with regular menstrual cycles and without contraindication for the use of OCs were included in the study according to the inclusion and exclusion criteria. The women had not used any hormonal preparation for at least four weeks prior to the study and did not use drugs that were known to influence the effects of OCs. A gynecological examination including a Papanicolaou smear and a pregnancy test, as well as the assessment of the

Results

Screening was carried out with 110 participants, among which 100 women were randomized and received medication. Eight participants discontinued prematurely from the study, and from one participant no data were available from the treatment phase. Therefore, 91 women completed the study. The statistical analysis was carried out with the data of all 99 participants who received any treatment and for whom data from the treatment phase were available (full-analysis set).

Treatment with the three

Discussion

Lipid metabolism may be affected by sex steroids in a dose- and time-dependent manner [2], [3], [4]. In general, treatment with potent estrogens increases the plasma concentrations of TG and the components of HDL and decreases those of LDL [5], whereas androgens and progestogens with androgenic activity may counteract the estrogen-dependent effects to a certain extent. Among the progestogens used in OCs, the progesterone derivatives possess no or only weak androgenic and partly antiandrogenic

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