Original research articleEffects of two combined oral contraceptives containing ethinyl estradiol 20 μg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism
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)
- et al.
The metabolic impact of oral contraceptives
Am. J. Obstet. Gynecol.
(1992) Metabolic effects of oral contraceptives
Am. J. Obstet. Gynecol.
(1987)Lipid metabolism effects with desogestrel-containing oral contraceptives
Am. J. Obstet. Gynecol.
(1993)Effects of desogestrel on carbohydrate metabolism
Am. J. Obstet. Gynecol.
(1993)Drospirenone: pharmacology and pharmacokinetics of a unique progestogen
Contraception
(2000)- et al.
Extending the duration of active oral contraceptive pills to manage hormone withdrawal symptoms
Obstet. Gynecol.
(1997) - et al.
The analysis of vaginal bleeding patterns induced by fertility regulating methods. World Health Organization special programme of research, development and research training in human reproduction
Contraception
(1986) - et al.
A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism
Contraception
(2003) - et al.
Comparison of the lipoprotein, carbohydrate, and hemostatic effects of phasic oral contraceptives containing desogestrel or levonorgestrel
Contraception
(2001) - et al.
Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism
Contraception
(2002)
A randomized study on the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on lipid and lipoprotein metabolism over a period of 13 cycles
Contraception
Effect of two oral contraceptives containing ethinyl estradiol and gestodene or norgestimate on different lipid and lipoprotein parameters
Contraception
A comparative metabolic study of two low-estrogen-dose oral contraceptives containing desogestrel or gestodene progestins
Am. J. Obstet. Gynecol.
A 12-month clinical investigation with a 24-day regimen containing 15 μg ethinylestradiol plus 60 μg gestodene with respect to hemostasis and cycle control
Contraception
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2016, International Journal of Gynecology and ObstetricsCitation 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.