Institute of Mathematics, University of the Philippines Diliman, Quezon City, Philippines.
Maritime Academy of Asia and the Pacific, Bataan, Philippines.
PLoS Comput Biol. 2023 Apr 13;19(4):e1010073. doi: 10.1371/journal.pcbi.1010073. eCollection 2023 Apr.
Anovulation refers to a menstrual cycle characterized by the absence of ovulation. Exogenous hormones such as synthetic progesterone and estrogen have been used to attain this state to achieve contraception. However, large doses are associated with adverse effects such as increased risk for thrombosis and myocardial infarction. This study utilizes optimal control theory on a modified menstrual cycle model to determine the minimum total exogenous estrogen/progesterone dose, and timing of administration to induce anovulation. The mathematical model correctly predicts the mean daily levels of pituitary hormones LH and FSH, and ovarian hormones E2, P4, and Inh throughout a normal menstrual cycle and reflects the reduction in these hormone levels caused by exogenous estrogen and/or progesterone. Results show that it is possible to reduce the total dose by 92% in estrogen monotherapy, 43% in progesterone monotherapy, and that it is most effective to deliver the estrogen contraceptive in the mid follicular phase. Finally, we show that by combining estrogen and progesterone the dose can be lowered even more. These results may give clinicians insights into optimal formulations and schedule of therapy that can suppress ovulation.
排卵障碍是指月经周期无排卵的一种状态。曾使用外源性孕激素和雌激素等激素来达到这种状态以实现避孕。然而，大剂量使用会导致血栓形成和心肌梗死等不良反应的风险增加。本研究利用改进的月经周期模型上的最优控制理论来确定诱导排卵所需的最小总外源性雌激素/孕激素剂量和给药时间。该数学模型正确预测了正常月经周期中垂体激素 LH 和 FSH 以及卵巢激素 E2、P4 和 Inh 的日平均水平，并反映了外源性雌激素和/或孕激素引起的这些激素水平的降低。结果表明，雌激素单药治疗可将总剂量降低 92%，孕激素单药治疗可降低 43%，在卵泡中期给予雌激素避孕药最为有效。最后，我们发现通过联合使用雌激素和孕激素，剂量可以进一步降低。这些结果可能为临床医生提供有关可抑制排卵的最佳配方和治疗方案的见解。
