Abstract
Background
Adequate folate supplementation in the periconceptional phase is recommended to reduce the risk of neural tube defects. Oral contraceptives may provide a reasonable delivery vehicle for folate supplementation before conception in women of childbearing potential. This study aimed to demonstrate that a fixed-dose combination of an oral contraceptive and levomefolate calcium leads to sustainable improvements in folate status compared with an oral contraceptive + folic acid.
Methods
This was a double-blind, randomized, parallel-group study in which 172 healthy women aged 18–40 years received ethinylestradiol (EE)-drospirenone-levomefolate calcium or EE-drospirenone + folic acid for 24 weeks (invasion phase), and EE-drospirenone for an additional 20 weeks (folate elimination phase). The main objective of the invasion phase was to examine the area under the folate concentration time-curve for plasma and red blood cell (RBC) folate, while the main objective of the elimination phase was to determine the duration of time for which RBC folate concentration remained ≥ 906 nmol/L after cessation of EE-drospirenone-levomefolate calcium.
Results
Mean concentration-time curves for plasma folate, RBC folate, and homocysteine were comparable between treatment groups during both study phases. During the invasion phase, plasma and RBC folate concentrations increased and approached steady-state after about 8 weeks (plasma) or 24 weeks (RBC). After cessation of treatment with levomefolate calcium, folate concentrations decreased slowly. The median time to RBC folate concentrations falling below 906 nmol/L was 10 weeks (95% confidence interval 8–12 weeks) after cessation of EE-drospirenone-levomefolate calcium treatment. Plasma and RBC folate levels remained above baseline values in 41.3% and 89.3% of women, respectively, at the end of the 20-week elimination phase.
Conclusion
Improvements in folate status were comparable between EE-drospirenone-levomefolate calcium and EE-drospirenone + folic acid. Plasma and RBC folate levels remained elevated for several months following cessation of treatment with EE-drospirenone-levomefolate calcium.
Acknowledgments
Funding for this study was provided by Bayer HealthCare Pharmaceuticals, the manufacturer of EE 0.030 mg–drospirenone 3 mg (Yasmin®) and EE-drospirenone-levomefolate calcium. The authors are grateful to Klaus Pietrzik for his stimulating discussions concerning the study design. The authors would also like to thank Guenter Michl (bioanalytics), Susanne Reschke (clinical pharmacokinetics), and Vijay Chauhan (clinical statistics).
Disclosure
The authors would like to thank Claire Byrne of inScience Communications, Springer Healthcare, for medical writing support during preparation of the manuscript, which was funded by Bayer HealthCare Pharmaceuticals. KD, DT, FE, BR, and HB are employees of Bayer HealthCare Pharmaceuticals. ML and MK are employees of Nuvisan GmbH, Neu-Ulm, Germany.