Misaligned hormonal rhythmicity: Mechanisms of origin and their clinical significance

Rhythmic hormonal secretion is key for sustaining health. While a central pacemaker in the hypothalamus is the main driver of circadian periodicity, many hormones oscillate with different frequencies and amplitudes. These rhythms carry information about healthy physiological functions, while at the same time they must be able to respond to external cues and maintain their robustness against severe perturbations. Since endocrine disruptions can lead to hormonal misalignment and disease, understanding the clinical significance of these rhythms can help support diagnosis and disease management. While the misalignment of dynamic hormone profiles can be quantitatively analysed though statistical and computational techniques, mathematical modelling can provide fundamental understanding about the mechanisms underpinning endocrine rhythms, particularly around the question of what makes them robust to some perturbations but fragile to others. In this study, I will review the key challenges of understanding hormonal rhythm misalignment from a mathematical perspective, including their causes and clinical significance. By reviewing modelling examples of coupled endocrine axes, I will address the question of how perturbations in one endocrine axis propagate to another, leading to the more complex issue of disentangling the contribution of each endocrine system to a robust dynamic environment.