Elsevier

Contraception

Volume 71, Issue 6, June 2005, Pages 409-416
Contraception

Original research article
Effects of two combined oral contraceptives containing ethinyl estradiol 20 μg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism

https://doi.org/10.1016/j.contraception.2004.12.005Get rights and content

Abstract

Objective

To compare the effect of ethinyl estradiol 20 μg/drospirenone 3 mg (EE 20 μg/DRSP 3 mg) administered according to a 24/4 regimen with ethinyl estradiol 20 μg/desogestrel 150 μg (EE 20 μg/DSG 150 μg) administered according to the conventional 21/7 regimen on lipid, carbohydrate and hemostatic parameters.

Study Design

In this open-label study, healthy women were randomized to EE 20 μg/DRSP 3 mg or EE 20 μg/DSG 150 μg for seven cycles. Mean differences in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels at cycle 7 compared to baseline were assessed. Secondary variables included changes in other lipid, hemostatic and carbohydrate parameters.

Results

Both treatments increased HDL-cholesterol, but decreased LDL-cholesterol by a comparable extent. Although slightly elevated in both groups, blood glucose and C-peptide levels measured during oral glucose tolerance tests were within normal reference ranges at cycle 7. Overall, the differences in lipid, hemostatic or carbohydrate parameters were not significant between the two treatments.

Conclusion

EE 20 μg/DRSP 3 mg has a good safety profile comparable with EE 20 μg/DSG 150 μg.

Introduction

Although combined oral contraceptives (OCs) are highly efficacious and have a good safety profile, their hormonal components are known to have various metabolic effects, including effects on lipid and carbohydrate metabolism, and hemostatic variables. For example, it is well known that androgenic progestins exert an adverse influence on lipid metabolism. This is in part due to their ability to counteract the favorable estrogen-induced changes in low-density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol levels [1], [2], [3], [4]. Furthermore, the influence on glucose metabolism increases with progesterone dominance [1], [5], [6], [7]. In contrast, the adverse effects on hemostatic variables and the associated risk of venous thrombosis are most likely to be influenced by the estrogen dose and not by the type of progestin [8].

Recent reviews have suggested that the ideal pharmacological properties of a synthetic progestin should resemble those of progesterone as closely as possible, while reducing or eliminating the undesirable (mainly androgenic and mineralocorticoid) effects [9], [10], [11]. Most currently available progestins are 19-nortestosterone derivatives and as such have inherent androgenic potential. Furthermore, of these progestins, none are able to counteract the mineralocorticoid activity of the estrogen component. In contrast, drospirenone has proven antiandrogenic properties and, as an analog of spironolactone, inherent antimineralocorticoid activity [9], [12], [13], [14].

A new contraceptive formulation and regimen based on drospirenone has been developed. The new formulation, ethinyl estradiol 20 μg/drospirenone 3 mg (EE 20 μg/DRSP 3 mg), is taken daily for an extended treatment period of 24 days followed by four hormone-free days (24/4 regimen). The 24/4 regimen was developed in part to accentuate the benefits of drospirenone and to alleviate symptoms such as pelvic pain, headaches, bloating and breast tenderness that are common (particularly during the 7-day hormone-free interval) in most women who adhere to the conventional regimen of 21 days of active treatment followed by seven hormone-free days (21/7 regimen) [15]. Extending the days on active treatment is expected to reduce hormone withdrawal effects.

This open, randomized study was designed to compare the effects of EE 20 μg/DRSP 3 mg administered according to a 24/4 regimen with ethinyl estradiol 20 μg/desogestrel 150 μg (EE 20 μg/DSG 150 μg) administered according to the conventional 21/7 regimen on the lipid profile, hemostatic and carbohydrate metabolism parameters.

Section snippets

Study design

This open-label, randomized, controlled study was conducted in a single center in The Netherlands. The study protocol was approved by an independent ethics committee and was conducted in accordance with both the Declaration of Helsinki (as revised in 1996) and the International Conference on Harmonization for Industry E6-Good Clinical Practice guidelines. All participants gave written and informed consent before enrolment.

Patients

Healthy women aged 18–35 years (including smokers up to the age of 30

Subject disposition

A total of 60 patients were randomized to receive EE 20 μg/DRSP 3 mg (n=30) or EE 20 μg/DSG 150 μg (n=30). Of these, 29 patients assigned to the EE 20 μg/DRSP 3 mg group and 30 assigned to the EE 20 μg/DSG 150 μg group were included in the FAS. Seven patients discontinued the study prematurely, four in the EE 20 μg/DRSP 3 mg group and three in the EE 20 μg/DSG 150 μg group. Reasons for discontinuation in the EE 20 μg/DRSP 3 mg group included continuous vaginal bleeding, irritable mood, headache

Discussion

This study showed that both EE 20 μg/DRSP 3 mg and EE 20 μg/DSG 150 μg have similar effects on lipid, hemostatic and carbohydrate parameters. Overall, these results suggest that extending the period of active treatment by 3 days per treatment cycle (24/4 regimen) does not have any negative influence on these parameters compared with the conventional 21/7 regimen. Furthermore, EE 20 μg/DRSP 3 mg demonstrated a safety profile comparable to other combined OCs with no reasons for any safety

Acknowledgments

This study was conducted in Nijmegen, The Netherlands, and supported by a grant from Schering A.

References (29)

Cited by (83)

  • Combined oral contraceptives: Why, when, where?

    2022, Polycystic Ovary Syndrome: Challenging Issues in the Modern Era of Individualized Medicine
  • Contraception and diabetes: Which modalities should we consider in 2021?

    2022, Annales d'Endocrinologie
    Citation Excerpt :

    These changes are, however, slight, as shown in a meta-analysis of 23 studies of combined contraception using desogestrel [16]. Berenson et al. found that, after 36 months’ use of a pill containing a 2nd or 3rd generation progestin, LDL-cholesterol levels improved from 113 to 100 mg/dl (P = 0.002), with a consequent slight improvement in LDL/HDL ratio [16,17]. Thus, these changes have no impact on atherosclerosis risk.

  • Comparison of two contraceptive pills containing drospirenone and 20 μg or 30 μg ethinyl estradiol for polycystic ovary syndrome

    2016, International Journal of Gynecology and Obstetrics
    Citation Excerpt :

    Previous evidence [22] shows that the atherosclerotic risk is not increased by an estrogen-induced rise in triglyceride levels if the level of high-density lipoprotein cholesterol remains high and the level of low-density lipoprotein cholesterol is not increased. Klipping and Marr [17] reported a good safety profile for drospirenone pills containing 20 μg EE as well as favorable changes in high- and low-density lipoprotein cholesterol, indicating potential cardioprotective benefits that were comparable to those observed with other pills. According to Beasley et al. [23] the presence of obesity has little effect on pill-induced changes in carbohydrate or lipid metabolism.

View all citing articles on Scopus
View full text