American Journal of Internal Medicine

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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

Received: 20 April 2016    Accepted: 29 April 2016    Published: 17 May 2016
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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.

DOI 10.11648/j.ajim.20160403.12
Published in American Journal of Internal Medicine (Volume 4, Issue 3, May 2016)
Page(s) 49-59
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Combination Oral Contraceptives, Ethinyl Estradiol, Levonorgestrel, Lipid Metabolism, Systematic Review and Meta-Analysis

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.
Author Information
  • The First Affiliated Hospital of Jinan University, Guangzhou, China

  • College of Pharmacy of Jinan University, Guangzhou, China

  • College of Pharmacy of Jinan University, Guangzhou, China

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    Lin Chen, Jun Xu, Shaohui Cai. (2016). 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, 4(3), 49-59. https://doi.org/10.11648/j.ajim.20160403.12

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    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. Am. J. Intern. Med. 2016, 4(3), 49-59. doi: 10.11648/j.ajim.20160403.12

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    AMA Style

    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. Am J Intern Med. 2016;4(3):49-59. doi: 10.11648/j.ajim.20160403.12

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  • @article{10.11648/j.ajim.20160403.12,
      author = {Lin Chen and Jun Xu and Shaohui Cai},
      title = {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},
      journal = {American Journal of Internal Medicine},
      volume = {4},
      number = {3},
      pages = {49-59},
      doi = {10.11648/j.ajim.20160403.12},
      url = {https://doi.org/10.11648/j.ajim.20160403.12},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ajim.20160403.12},
      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.},
     year = {2016}
    }
    

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  • TY  - JOUR
    T1  - 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
    AU  - Lin Chen
    AU  - Jun Xu
    AU  - Shaohui Cai
    Y1  - 2016/05/17
    PY  - 2016
    N1  - https://doi.org/10.11648/j.ajim.20160403.12
    DO  - 10.11648/j.ajim.20160403.12
    T2  - American Journal of Internal Medicine
    JF  - American Journal of Internal Medicine
    JO  - American Journal of Internal Medicine
    SP  - 49
    EP  - 59
    PB  - Science Publishing Group
    SN  - 2330-4324
    UR  - https://doi.org/10.11648/j.ajim.20160403.12
    AB  - 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.
    VL  - 4
    IS  - 3
    ER  - 

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