Optimizing oral contraceptive timing: Daytime intake reduces doses and enhances efficacy.

Contraception is essential for reproductive health and women's empowerment because it allows informed choices about pregnancy prevention. Oral contraceptives (OCs) are a popular method due to their accessibility and high level of effectiveness in attaining contraception through the suppression of ovulation. However, current OC regimens do not consider circadian hormonal rhythms, which significantly influence hormone secretion and drug metabolism. Accounting for circadian rhythms may further reduce the dosage of current formulations, which pose risks, including an increased likelihood of venous thromboembolism. We addressed this gap by developing a mathematical model that integrates circadian rhythms with contraceptive pharmacokinetics. Our results show that daytime OC dosing reduces the required ethinyl estradiol (EE) dose by about 6% and the required dienogest (DNG) dose by about 52% compared to evening dosing, due to the alignment of EE and DNG concentrations with luteinizing hormone production peaks. We further lowered the EE dose by about 67% using an optimal nonconstant regimen and decreased the number of intake days from 21 to 8. This dual-timescale optimization demonstrates how incorporating circadian rhythms can significantly enhance contraceptive regimens, enabling safer and more effective dosing strategies with broader implications for chronopharmacological interventions.