Chronic intermittent hypoxia-induced hypertension: the impact of sex hormones

Abstract

Obstructive sleep apnea, a common form of sleep-disordered breathing, is characterized by intermittent cessations of breathing that reduce blood oxygen levels and contribute to the development of hypertension. Hypertension is a major complication of obstructive sleep apnea that elevates the risk of end-organ damage. Premenopausal women have a lower prevalence of obstructive sleep apnea and cardiovascular disease than men and postmenopausal women, suggesting that sex hormones play a role in the pathophysiology of sleep apnea-related hypertension. The lack of protection in men and postmenopausal women implicates estrogen and progesterone as protective agents but testosterone as a permissive agent in sleep apnea-induced hypertension. A better understanding of how sex hormones contribute to the pathophysiology of sleep apnea-induced hypertension is important for future research and possible hormone-based interventions. The effect of sex on the pathophysiology of sleep apnea and associated intermittent hypoxia-induced hypertension is of important consideration in the screening, diagnosis, and treatment of the disease and its cardiovascular complications. This review summarizes our current understanding of the impact of sex hormones on blood pressure regulation in sleep apnea with a focus on sex differences.

Keywords: estrogens; hypertension; sleep apnea; sympathetic nervous system; testosterone.

Figure 1.

Effects of testosterone (T) on the mechanisms of CIH hypertension. CIH generates hypoxia and reoxygenations leading to increased oxidative stress, generation of RAS-mediated angiotensin II, vascular dysfunction, and autonomic imbalance that leads to hypertension. Bold arrows show pathophysiological mechanisms driving CIH hypertension in an intersystem (CNS, renal, cardiovascular, and respiratory) interplay. Testosterone’s effects on CIH hypertension are shown in the boxes. Created with BioRender. CIH, chronic intermittent hypoxia; CNS, central nervous system; RAS, renin-angiotensin system. The numbers indicate references.

Figure 2.

Ovarian hormones (estrogen and progesterone) protect intact/premenopausal females from CIH hypertension by interfering with ROS generation and oxidative stress, preserving vascular function, attenuating angiotensin II (ANG II) effects and exaggerated sympathoactivation. Bold arrows illustrate pathophysiological mechanisms driving CIH hypertension in an intersystem (CNS, renal, cardiovascular, and respiratory) interplay. Dashed arrows show the interferences of estrogen (E₂) and progesterone (PG) on the mechanisms of CIH to protect intact/premenopausal females from CIH hypertension. Created with BioRender. CIH, chronic intermittent hypoxia; CNS, central nervous system; ROS, reactive oxygen species. The numbers indicate references.