Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use

Abstract

Objectives To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG).

Methods Randomised, open-label, multicentre, comparative substudy of a larger phase 3 trial involving 147 healthy women (age 18−49 years). Participants received the COC either continuously (levonorgestrel [LNG] 90 μg/ethinylestradiol [EE] 20 μg) or cyclically (21/7 days pattern; LNG 100 μg/EE 20 μg).

Results After 13 pill packs, changes in total cholesterol (+0.23 vs. −0.06 mmol/l), low-density lipoprotein cholesterol (+0.25 vs. −0.12 mmol/l), and high-density lipoprotein cholesterol₃ (−0.06 vs. −0.15 mmol/l) differed significantly (p<0.05) between the continuous and cyclic regimens, respectively. Increases were significantly greater (p <0.05) for protein C antigen (+11.8% vs. +6.1%) and SHBG (+791 vs. +565 nmol/l), and significantly smaller (p <0.05, ranks) for D-dimer (+19 vs. +37 μg FE/l).

Conclusions Overall, the continuous and cyclic regimens affected metabolic variables similarly. The larger increase in SHBG with the continuous COC is consistent with a higher net oestrogenic effect due to a lower daily dose of LNG. Prospective studies are required to determine the long-term effects of this continuous COC regimen.

Keywords:

• Continuous oral contraceptive
• Ethinylestradiol
• Levonorgestrel

Acknowledgements

The authors wish to thank Lynne Smith for statistical analysis, and Kathleen Ohleth, PhD, at Precise Publications, LLC, for editorial and medical writing support, which was funded by Wyeth and Pfizer Inc.

Declaration of interest: The study was sponsored by Wyeth, which was acquired by Pfizer Inc. in October 2009. Mandana Rad, Cornelis Kluft, Marieke L. de Kam, Piet Meijer, Adam F. Cohen, and Jacobus Burggraaf received support for completion of the study and analyses from Wyeth, which was acquired by Pfizer Inc. in October 2009. Gary S. Grubb was an employee of Wyeth Research at the time the study was conducted. Ginger D. Constantine was an employee of Wyeth Research and then Pfizer after the acquisition in October 2009.