The Effect of Dose-Reduced Combination Oral Contraceptives Containing 20 µg of Ethinyl Estradiol and 100 µg of Levonorgestrel on Lipid Metabolism: A Meta-Analysis
American Journal of Internal Medicine
Volume 4, Issue 3, May 2016, Pages: 49-59
Received: Apr. 20, 2016; Accepted: Apr. 29, 2016; Published: May 17, 2016
Views 3679      Downloads 113
Authors
Lin Chen, The First Affiliated Hospital of Jinan University, Guangzhou, China
Jun Xu, College of Pharmacy of Jinan University, Guangzhou, China
Shaohui Cai, College of Pharmacy of Jinan University, Guangzhou, China
Article Tools
Follow on us
Abstract
Lipid metabolic disturbance induced by the synthetic steroids used in combination oral contraceptives (COCs) has been considered as one of the potential risk factors of cardiovascular diseases. A lower-dose preparation that contains 20 µg of ethinyl estradiol and 100 µg of levonorgestrel (20EE/LNG) has proven effective in most clinical studies, whereas its effect on lipid metabolism is still unclear. The purpose of this study was to estimate the effect of a lower dose of a COC (containing 20 µg of ethinyl estradiol and 100 µg of levonorgestrel) on lipid metabolism by conducting a systematic review and a meta-analysis. A literature search was performed using MEDLINE (PubMed), Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL database). The studies that are randomized controlled trials to compare a lower-dose COC (20EE/LNG) with a placebo or another COC that differed in terms of the drug, dosage, regimen, and study length were included. Meanwhile, studies should have evaluated the index of lipid metabolism changes. However, the studies with the interventions fewer than three consecutive cycles or the patients were primarily used the treatment of non-contraceptive were excluded. We pooled the low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) results, and compared 20EE/LNG with conventional-dose COCs using fixed-effects meta-analysis with inverse-variance weighting. Five randomized controlled trials, with a total of 423 participants (age range: 18–35 years), were included in this study. The results derived from all the included studies were pooled. LDL-C of 20EE/LNG group showed significant lower than control group after three (SMD, 0.16; 95% CI, 0.03–0.30; P=0.02) and six (SMD, 0.16; 95% CI, 0.01–0.31; P=0.04) cycles of treatment. However, there was no difference between the two groups after 12 cycles of administration (SMD, -0.06; 95% CI, -0.31 to 0.18; P=0.61). The pooled results showed there was a significant increase in HDL-C in the 20EE/LNG group after three cycles of treatment (SMD, 0.43; 95% CI, 0.13–0.73; P=0.005). No significant difference was observed between TC and TG groups. For LDL-C, the low-dose group shows a higher risk of suffering from cardiovascular diseases after three and six cycles of treatment, while no difference is observed after 12 cycles of treatment. For HDL-C, the 20EE/LNG group exhibits favorable effects after three cycles of treatment compared with the control groups. Similar effects are found between TC and TG profiles groups.
Keywords
Combination Oral Contraceptives, Ethinyl Estradiol, Levonorgestrel, Lipid Metabolism, Systematic Review and Meta-Analysis
To cite this article
Lin Chen, Jun Xu, Shaohui Cai, The Effect of Dose-Reduced Combination Oral Contraceptives Containing 20 µg of Ethinyl Estradiol and 100 µg of Levonorgestrel on Lipid Metabolism: A Meta-Analysis, American Journal of Internal Medicine. Vol. 4, No. 3, 2016, pp. 49-59. doi: 10.11648/j.ajim.20160403.12
Copyright
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
References
[1]
Meade, T. W., G. Greenberg and S.G. Thompson, Progestogens and cardiovascular reactions associated with oral contraceptives and a comparison of the safety of 50- and 30-microgram oestrogen preparations. Br Med J, 1980. 280(6224): p. 1157-61.
[2]
Mishell, D. J., Use of oral contraceptives in women of older reproductive age. Am J Obstet Gynecol, 1988. 158(6 Pt 2): p. 1652-7.
[3]
Gordon, T., et al., High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med, 1977. 62(5): p. 707-14.
[4]
Navab, M., et al., HDL as a biomarker, potential therapeutic target, and therapy. Diabetes, 2009. 58(12): p. 2711-7.
[5]
Godsland, I. F., et al., The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med, 1990. 323(20): p. 1375-81.
[6]
Aurell, M., K. Cramer and G. Rybo, Serum lipids and lipoproteins during long-term administration of an oral contraceptive. Lancet, 1966. 1(7432): p. 291-3.
[7]
Endrikat, J., et al., An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables. Contraception, 2002. 65(3): p. 215-21.
[8]
Wiegratz, I., et al., Effect of dienogest-containing oral contraceptives on lipid metabolism. Contraception, 2002. 65(3): p. 223-9.
[9]
Scharnagl, H., et al., Double-blind, randomized study comparing the effects of two monophasic oral contraceptives containing ethinylestradiol (20 microg or 30 microg) and levonorgestrel (100 microg or 150 microg) on lipoprotein metabolism. Contraception, 2004. 69(2): p. 105-13.
[10]
Skouby, S. O., et al., A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel. Contraception, 2005. 71(2): p. 111-7.
[11]
Catenacci, V. A., J. O. Hill and H. R. Wyatt, The obesity epidemic. Clin Chest Med, 2009. 30(3): p. 415-44, vii.
[12]
Archer, D. F., et al., Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol (Alesse). North american Levonorgestrel Study Group (NALSG). Am J Obstet Gynecol, 1999. 181(5 Pt 2): p. 39-44.
[13]
Archer, D. F., et al., A new low-dose monophasic combination oral contraceptive (Alesse) with levonorgestrel 100 micrograms and ethinyl estradiol 20 micrograms. North American Levonorgestrel Study Group (NALSG). Contraception, 1997. 55(3): p. 139-44.
[14]
Crook, D. and I. Godsland, Safety evaluation of modern oral contraceptives. Effects on lipoprotein and carbohydrate metabolism. Contraception, 1998. 57(3): p. 189-201.
[15]
Rosenberg, M. J., A. Meyers and V. Roy, Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 micrograms and 35 micrograms estrogen preparations. Contraception, 1999. 60(6): p. 321-9.
[16]
Crook, D. and I. Godsland, Safety evaluation of modern oral contraceptives. Effects on lipoprotein and carbohydrate metabolism. Contraception, 1998. 57(3): p. 189-201.
ADDRESS
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
U.S.A.
Tel: (001)347-983-5186