Mechanistic model of hormonal contraception

PLoS Comput Biol. 2020 Jun 29;16(6):e1007848. doi: 10.1371/journal.pcbi.1007848. eCollection 2020 Jun.

Abstract

Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Contraceptive Agents / therapeutic use*
  • Estrogens / therapeutic use
  • Female
  • Follicle Stimulating Hormone / physiology
  • Hormonal Contraception*
  • Humans
  • Hypothalamus / drug effects
  • Luteinizing Hormone / physiology
  • Menstrual Cycle / drug effects*
  • Models, Biological
  • Ovary / drug effects
  • Pituitary Gland / drug effects
  • Progestins / therapeutic use*

Substances

  • Contraceptive Agents
  • Estrogens
  • Progestins
  • Luteinizing Hormone
  • Follicle Stimulating Hormone

Grants and funding

JFS and AAW were funded in part by the National Science Foundation Division of Mathematical Sciences (DMS) award number 1225607 (https://www.nsf.gov/div/index.jsp?div=DMS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.