Toward an optimal contraception dosing strategy

PLoS Comput Biol. 2023 Apr 13;19(4):e1010073. doi: 10.1371/journal.pcbi.1010073. eCollection 2023 Apr.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anovulation*
  • Contraception
  • Estradiol
  • Estrogens
  • Female
  • Humans
  • Luteinizing Hormone
  • Progesterone* / pharmacology

Substances

  • Progesterone
  • Luteinizing Hormone
  • Estradiol
  • Estrogens

Grants and funding

BLAG was supported by University of the Philippines Office of International Linkages, a Continuous Operational and Outcomes-based Partnership for Excellence in Research and Academic Training Enhancement (UP-OIL-COOPERATE) grant, and a Commission on Higher Education Faculty Development Program - II (CHED-FDP-II) scholarship. AADLRV acknowledges the support of the Institute of Mathematics, University of the Philippines Diliman and the Institute for Basic Science (IBS-R029-C3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.