Reduced model for female endocrine dynamics: Validation and functional variations

A normally functioning menstrual cycle requires significant crosstalk between hormones originating in ovarian and brain tissues. Reproductive hormone dysregulation may cause abnormal function and sometimes infertility. The inherent complexity in this endocrine system is a challenge to identifying mechanisms of cycle disruption, particularly given the large number of unknown parameters in existing mathematical models. We develop a new endocrine model to limit model complexity and use simulated distributions of unknown parameters for model analysis. By employing a comprehensive model evaluation, we identify a collection of mechanisms that differentiate normal and abnormal phenotypes. We also discover an intermediate phenotype- displaying relatively normal hormone levels and cycle dynamics-that is grouped statistically with the irregular phenotype. Results provide insight into how clinical symptoms associated with ovulatory disruption may not be detected through hormone measurements alone.

Automated summary

A normally functioning menstrual cycle requires communication between hormones in the ovaries and brain tissues. Hormonal dysregulation can lead to abnormal function and infertility. Developing a new endocrine model and using simulated unknown parameters, we identified mechanisms that differentiate normal and abnormal phenotypes. We also discovered an intermediate phenotype, showing normal hormone levels and cycle dynamics, statistically similar to the irregular phenotype. This study highlights the importance of considering clinical symptoms in addition to hormone measurements.