Sophie Fischer-Holzhausen

Dissertation: May 5th, at 13:15-15:30, 2023

Location: Høyteknologisenteret, lille auditorium

Title of thesis: “A matter of timing: A modelling-based investigation of the dynamic behaviour of reproductive hormones in girls and women”.

External link to event here.

Link to press release in Norwegian here.

Summary of thesis: 

The hypothalamic-pituitary-gonadal axis (HPG axis), a part of the human endocrine system, regulates the female reproductive function. Feedback interactions between hormones secreted from the glands forming the HPG axis are essential for establishing a regular menstrual cycle. Mathematical models predicting the time evolution of hormone concentrations and the maturation of ovarian follicles are useful tools  for understanding the dynamic behaviour of the menstrual cycle. Such models can, for example, help us to investigate pathological conditions, such as endometriosis or Polycystic Ovary Syndrome. Furthermore, they can be used to systematically study the effects of drugs on the endocrine system. In doing so, menstrual cycle models could potentially be integrated into clinical routines as clinical decision support systems. For the simulation-based investigation of hormonal treatments aiming to stimulate the growth of ovarian follicles (Controlled Ovarian Stimulation (COS)), we need models that predict hormone concentrations and the maturation of ovarian follicles in biological units throughout consecutive cycles. Here, I propose such a mechanistic menstrual cycle model. I also demonstrate its capability to predict the outcome of COS. Individual time series data is usually used to calibrate mechanistic models having clinical implications. Collecting these data, however, is time consuming and requires a high commitment from study participants. Therefore, integrating different data sets into the model calibration process is of interest. One type of data that is often more feasible to collect than individual time series is cross sectional data. As part of my thesis, I developed a workflow based on Bayesian updating to integrate cross-sectional data into the model calibration process. I demonstrate the workflow using a mechanistic model describing the time evolution of reproductive hormones during puberty in girls. Exemplary, I show that a model calibrated with cross-sectional data can be used to predict individual dynamics after updating a subset of model parameters. In addition to the scientific contributions of this thesis, I hope that it creates attention for the importance of research in the area of women’s reproductive health and underpins the value of mathematical modelling for this field.