Ovariectomy, but not moderate intermittent hypoxia, promotes respiratory instability and risk of obesity in adult female rats.

Sleep apnoea (SA) is a prevalent and complex respiratory disorder associated with recurrent interruptions of air flow during sleep. SA causes sleep fragmentation and intermittent hypoxia which leads to numerous negative health consequences. While SA is typically more common in men, its prevalence in women increases sharply after menopause, implicating the loss of ovarian hormones in its pathogenesis. Despite the potential of hormone replacement therapy to modulate SA, the physiological mechanisms linking loss of ovarian function to SA remain unclear. Using an integrative approach, we investigated the combined effects of surgical removal of the ovaries (ovariectomy; OVX) and a 7-day moderate intermittent hypoxia protocol (IH; 30s at F i O 2 0.10, 10 cycles/h, 8 h/day) on respiratory, metabolic, cardiovascular and neuroendocrine regulation, including hypothalamic-pituitary-adrenal (HPA) axis activation and leptin levels in adult female rats. OVX increased apnoea frequency, respiratory instability and ventilatory responses to O2 (10%, 120 s) but not CO2 (5%, 10 min). However, contrary to our hypothesis, moderate IH did not worsen metabolic or cardiorespiratory dysfunction caused by OVX. OVX did not affect mean arterial pressure or heart rate but augmented weight gain and activated the HPA axis. Thus, our results indicate that OVX independently promotes apnoeas and activation of the stress axis and this is not worsened by additional exposure to moderate IH. This underscores the predominant role of ovarian hormone deficiency in SA-related pathophysiologies, highlighting menopause as a critical window for vulnerability to respiratory problems.