Is obstructive sleep apnea associated with cortisol levels? A systematic review of the research evidence

Abstract

The pathophysiology of obstructive sleep apnea (OSA) has been associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis; however a relationship between OSA and altered cortisol levels has not been conclusively established. We conducted a systematic review using the PRISMA Guidelines based on comprehensive database searches for (1) studies of OSA patients compared to controls in whom cortisol was measured and (2) studies of OSA patients treated with continuous positive airway pressure (CPAP) in whom cortisol was measured pre and post treatment. Five electronic databases were searched along with the reference lists of retrieved studies. The primary outcomes were (1) differences in cortisol between OSA and control subjects and (2) differences in cortisol pre-post CPAP treatment. Sampling methodology, sample timing and exclusion criteria were evaluated. Fifteen studies met the inclusion criteria. Heterogeneity of studies precluded statistical pooling. One study identified differences in cortisol between OSA patients and controls. Two studies showed statistically significant differences in cortisol levels pre-post CPAP. The majority of studies were limited by assessment of cortisol at a single time point. The available studies do not provide clear evidence that OSA is associated with alterations in cortisol levels or that treatment with CPAP changes cortisol levels. Methodological concerns such as infrequent sampling, failure to match comparison groups on demographic factors known to impact cortisol levels (age, body mass index; BMI),and inconsistent control of variables known to influence HPA function may have limited the results.

Sleep apnoea and the hypothalamic–pituitary–adrenal axis in men and women: effects of continuous positive airway pressure

“…Methodological limitations such as single blood draws, lack of a control group, failure to match comparison groups (e.g. by age and body mass index (BMI)) and inadequate control of variables known to affect HPA function may be the underlying factors of these inconsistent findings [13].…”

“…Furthermore, studies on the association between cortisol levels and sleep apnoea have focused mainly on obese middle-aged male populations, whereas data in nonobese men as well as women are lacking [13]. Obesity is the strongest risk factor for sleep apnoea, but also a known HPA axis modulator, and thus a possible confounder of the association between sleep apnoea and HPA axis activity [11].…”

“…Given the above limitations, it is no surprise that studies on the effects of continuous positive airway pressure (CPAP) treatment on HPA axis activity have yielded inconsistent findings [8,10,11,[13][14][15][16][17]. In addition, most of the CPAP studies have been confounded by methodological limitations such as lack of a control group at baseline, or a placebo control group, as well as a small sample size.…”

Association of salivary-assessed oxytocin and cortisol levels with time of night and sleep stage

“…She also suggests that oxytocin may have an etiological role in the development of psychiatric disorders, including depression, anxiety, and autism spectrum disorders, which are characterized by sleep disturbances (Hollander et al 2003;Panksepp 2006). Cortisol has been proposed as implicated in other sleep disorders, such as obstructive sleep apnea (Tomfohr et al 2012) and insomnia (Bonnet and Arand 2010). These biomarkers may thus be important for investigating the etiology and maintenance of these sleep disorders.…”

Sleep disordered breathing and autonomic function in overweight and obese children and adolescents

“…Cortisol is the primary human glucocorticoid product of the HPA axis and it is thereby expected that cortisol levels would be higher in patients with OSA. Literature linking HPA function and OSA in adults has been conflicting [19], and data from children is scarce.…”