Modeling “Abnormal” Ovulatory Dynamics: Enzymes, Insulin, and the Impact of Stress

<p>This work focuses on modeling the impact of stress on ovulatory dynamics. We develop a mathematical model of endocrine processes including gonadotropin-releasing hormone, kisspeptin signaling, and the ovulatory cycle. Integral to our model development, we define ovulatory criteria, conduct an extensive global sensitivity analysis, and fit parameters to clinical hormone data throughout the ovulatory cycle. We then incorporate four biological pathways through which stress may interact with the ovulatory cycle – increased aromatase activity, hyperinsulinemia, suppression of luteinizing hormone (LH), and the influence of cortisol on kisspeptin signaling. High levels of simulated chronic stress cause significant disruption of the ovulatory cycle. Investigating the impact of acute stress, we find temporal dependence upon ovulatory phases: early-cycle acute stress results in early ovulation, while mid-cycle acute stress delays ovulation. Finally, we replicate and experimentally expand upon clinical studies which use kisspeptin to treat stress-induced ovulatory dysfunction. We find that kisspeptin treatments can stimulate the necessary LH surge. However, other clinical markers may indicate unsuccessful restoration of ovulation, prolonged doses yield reduced results, and dysfunction returns after the conclusion of the treatment period.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Open Access

Discipline thesis:degree_discipline

Mathematics

Year

2026

Author dc:creator

• Williams, Savannah E.

Repository record dc:identifier

https://repository.brynmawr.edu/dissertations/275

OAI identifier oai:identifier

oai:repository.brynmawr.edu:dissertations-1277