Gender Differences in the Context of Obstructive Sleep Apnea and Metabolic Diseases.

Fátima O Martins,Sílvia V Conde

doi:10.3389/fphys.2021.792633

Abstract

The relationship between obstructive sleep apnea (OSA) and endocrine and metabolic disease is unequivocal. OSA, which is characterized by intermittent hypoxia and sleep fragmentation, leads to and exacerbates obesity, metabolic syndrome, and type 2 diabetes (T2D) as well as endocrine disturbances, such as hypothyroidism and Cushing syndrome, among others. However, this relationship is bidirectional with endocrine and metabolic diseases being considered major risk factors for the development of OSA. For example, polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, is significantly associated with OSA in adult patients. Several factors have been postulated to contribute to or be critical in the genesis of dysmetabolic states in OSA including the increase in sympathetic activation, the deregulation of the hypothalamus-pituitary axis, the generation of reactive oxygen species (ROS), insulin resistance, alteration in adipokines levels, and inflammation of the adipose tissue. However, probably the alterations in the hypothalamus-pituitary axis and the altered secretion of hormones from the peripheral endocrine glands could play a major role in the gender differences in the link between OSA-dysmetabolism. In fact, normal sleep is also different between men and women due to the physiologic differences between genders, with sex hormones such as progesterone, androgens, and estrogens, being also connected with breathing pathologies. Moreover, it is very well known that OSA is more prevalent among men than women, however the prevalence in women increases after menopause. At the same time, the step-rise in obesity and its comorbidities goes along with mounting evidence of clinically important sex and gender differences. Metabolic and cardiovascular diseases, seen as a men's illness for decades, presently are more common in women than in men and obesity has a higher association with insulin-resistance-related risk factors in women than in men. In this way, in the present manuscript, we will review the major findings on the overall mechanisms that connect OSA and dysmetabolism giving special attention to the specific regulation of this relationship in each gender. We will also detail the gender-specific effects of hormone replacement therapies on metabolic control and sleep apnea.

Highlights

Obstructive sleep apnea (OSA), the most common sleep disorder, is characterized by disturbances in sleep patterns namely arousals, snoring, and recurrent episodes of cessation of breathing airflow or airflow reduction leading to excessive daytime somnolence, difficulty in concentrating, or headaches
obstructive sleep apnea (OSA) severity is classified based on the apnea-hypopnea index (AHI) and oxygen desaturation levels, which are measured in a polysomnography study
In the first report on sleep disorder prevalence, published in the 1990s and based on the Wisconsin Cohort Study (WSCS), sleep-disordered breathing prevalence characterized as an AHI of 5 or higher was described to be 9% for women and 24% for men (Young et al, 1993)

Summary

INTRODUCTION

Obstructive sleep apnea (OSA), the most common sleep disorder, is characterized by disturbances in sleep patterns namely arousals, snoring, and recurrent episodes of cessation of breathing airflow (apnea) or airflow reduction (hypopnea) leading to excessive daytime somnolence, difficulty in concentrating, or headaches. This idea was first supported by a study in mice submitted to CIH in where CSN denervation prevented the development of CIH-induced fasting hyperglycemia and hepatic glucose output (Shin et al, 2014) Supporting this link between the CB, dysmetabolism, and OSA, several studies demonstrated that the CB has a key role in the control of peripheral insulin sensitivity and glucose homeostasis since: (1) CSN resection prevents and reverses insulin resistance, glucose intolerance and dyslipidemia, which are pathological dysmetabolic characteristics, in hypercaloric diet rats (Ribeiro et al, 2013; Sacramento et al, 2017, 2018); (2) CSN resection prevents and normalizes the overactivation of the sympathetic nervous system associated with the intake of hypercaloric diets in rats (Ribeiro et al, 2013; Sacramento et al, 2017; Cracchiolo et al, 2019); and (3) CB activity is increased in animal models of metabolic syndrome and diabetes (Ribeiro et al, 2013; Dos Santos et al, 2018; Cracchiolo et al, 2019) and in prediabetic patients (Cunha-Guimaraes et al, 2020). Nutritional and behavioral treatments to achieve weight loss have been seen as beneficial in improving respiratory function (Pasquali et al, 1988) and metabolic abnormalities (Muscelli et al, 1997) with a higher extent for men than women (Newman et al, 2005)

CONCLUSION

Findings

DATA AVAILABILITY STATEMENT