Original ArticleImpact of sleep-disordered breathing on metabolic dysfunctions in patients with polycystic ovary syndrome
Introduction
Polycystic ovary syndrome (PCOS) is one of the most prevalent (5–10%) gynecological conditions in premenopausal women [1], [2]. It is characterized by anovulation, hyperandrogenism, insulin resistance (IR), obesity, and polycystic ovaries [3], [4]. The pathogenesis of PCOS is multifactorial, with IR and compensatory hyperinsulinemia being the key factors. Insulin plays a direct role by acting synergistically with luteinizing hormone (LH) to stimulate androgen secretion from theca cells [5]. It also exerts an indirect effect by decreasing the sex hormone-binding globulin (SHBG) production from the liver, further enhancing androgen levels. This androgenic milieu inhibits the selection of dominant follicles, resulting in accumulation of dysfunctional cystic follicles in the ovary and anovulation [6], [7], [8].
Though the clinical presentation of most of these patients shows oligomenorrhea, hirsutism, and obesity, it is the metabolic dysfunctions that can have far-reaching, serious consequences. Several studies have shown that women with PCOS are prone to metabolic disorders such as glucose intolerance, type II diabetes mellitus (DM), hypertension, dyslipidemia, and cardiovascular diseases such as hypertension, stroke, and coronary artery disease (CAD) [9], [10], [11], [12], [13], [14], [15]. A recent addition to this list of health risks is obstructive sleep apnea (OSA), which has been reported to be higher in women with PCOS in comparison to the general population [6].
Sleep-disordered breathing (SDB) is characterized by repeated episodes of partial or complete cessation of breathing for ≥10 s during sleep. It constitutes a spectrum of disorders of varying severity with intermittent snoring as the mildest and obesity hypoventilation syndrome as the most severe. Heavy snoring, upper airway resistance syndrome, and mild/moderate/severe OSA lie between these two extremes [16]. Prevalence of SDB in women increases with age and body mass index (BMI), and has been reported to be between 2% and 9% [17], [18].
The pathogenesis of SDB involves a number of interrelated mechanisms such as anatomically small upper airway and abnormal respiratory control mechanism. The risk of OSA is increased as a function of both total body mass and its distribution. The quantity of visceral fat appears to correlate highly with OSA [19]. Testosterone hormone has also been shown to be a contributory factor in the development of SDB [20]. However, estrogen and progesterone are found to be protective [21].
SDB has several adverse outcomes on the cardiovascular system with increased prevalence of hypertension, CAD, ischemic heart disease (IHD), and stroke. It is also associated with increased prevalence of IR, glucose intolerance, type II DM, and dyslipidemia [22], [23], [24], [25].
The overall prevalence of both SDB and PCOS in general population is similar, ranging from 2% to 10%. Both of these conditions have very similar metabolic and cardiovascular complications, indicating a close association between the two.
We hypothesized that SDB is an independent risk factor contributing to the metabolic dysfunctions in women having PCOS. To test this hypothesis, we decided to study the impact of SDB on metabolic dysfunctions in patients with PCOS.
Section snippets
Methods
This was a cross-sectional study in which 50 women with PCOS attending the gynecology outpatient department and reproductive endocrinology clinic of Vardhaman Mahavir Medical College (VMMC) and Safdarjung Hospital were randomly selected.
PCOS was defined by the Rotterdam criteria, that is, the presence of any two of the following three features: (1) chronic oligomenorrhea (six or fewer spontaneous menses per year); (2) biochemical or clinical evidence of hyperandrogenism; and (3) polycystic
Results
Fifty women with PCOS participated in this study. On the basis of the PSG findings, 33 (66%) women were diagnosed with SDB. Demographic and clinical characteristics of women with PCOS and SDB (group 1) as well as women having PCOS without SDB (group 2) are shown in Table 1. BMI and waist circumference of women in group 1 were significantly higher than those in group 2 (P <0.001 in both). Further, 81.8% of women in group 1 and only 17.6% of women in group 2 had a waist circumference >88 cm,
Discussion
This study was undertaken with the aim of determining the effect of SDB on the metabolic dysfunctions seen in patients with PCOS. In this study, we have shown that there are several anthropometric and metabolic parameters that are significantly deranged in the patients having PCOS with SDB compared with those who do not have SDB.
Hyperandrogenemia is a hallmark and diagnostic criterion for PCOS. Its manifestation may be biochemical in the form of raised free testosterone and DHEAS levels, and
Conflict of interest
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2014.06.023.
Acknowledgements
We thank Dr Ayan Jha, Scientist Grade C, ICMR, New Delhi, for help in statistical analysis and Miss Shalu Soni for her secretarial help. Our gratitude extends to the colleagues at VMMC and Safdarjung Hospital and, most importantly, to our patients for their co-operation.
References (49)
- et al.
Polycystic ovary syndrome and obstructive sleep apnea
Sleep Med Clin
(2008) - et al.
Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institute of Health 1990 criteria
Fertil Steril
(2010) Medical progress: polycystic ovary syndrome
N Engl J Med
(2005)Polycystic ovary syndrome
N Engl J Med
(1995)Polycystic ovary syndrome
Obstet Gynecol
(2004)Diagnostic criteria in polycystic ovary syndrome
Semin Reprod Med
(2003)- et al.
Hyperandrogenism does not influence metabolic parameters in adolescent girls with PCOS
Int J Endocrinol
(2012) - et al.
Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance
J Clin Endocrinol Metab
(2001) - et al.
Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptors and using inositolglycan mediators as the signal transduction system
J Clin Endocrinol Metab
(1998) - et al.
A survey of the polycystic ovary syndrome in the Greek Island of Lesbos: hormonal and metabolic profile
J Clin Endocrinol Metab
(1999)
Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus
Am J Med
Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome
Diabetes Care
Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective controlled study in 254 affected women
J Clin Endocrinol Metab
Banting lecture 1988: role of insulin resistance in human disease
Diabetes
Insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension: parallels between human disease and rodent models
Diabetes Care
Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance
N Engl J Med
International classification of sleep disorders: diagnostic and coding manual
The occurrence of sleep-disordered breathing among middle aged adults
N Engl J Med
Prevalence of sleep disordered breathing in middle aged Korean men and women
Am J Respir Crit Care Med
Visceral fat accumulation as an important risk factor for obstructive sleep apnoea syndrome in obese subjects
J Intern Med
Sleep apnea and neuroendocrine function
Sleep Med Clin
Prevalence of sleep disordered breathing in women: effects of gender
Am J Respir Crit Care Med
Prospective study of the association of sleep disordered breathing and hypertension
N Engl J Med
Obstructive sleep apnea–hypopnea and incident stroke: the Sleep Heart Health Study
Am J Respir Crit Care Med
Cited by (32)
Nonalcoholic fatty liver disease and obstructive sleep apnea in women with polycystic ovary syndrome
2022, Fertility and SterilityCitation Excerpt :Evidence for an increase in the risk of OSA among women with PCOS has been confirmed in more recent studies. In a prospective cross-sectional study of 50 women with PCOS, the prevalence of OSA was high at 66% (92). In this study, women with PCOS who had OSA were more likely to have obesity and had significantly higher glucose and TG levels and a higher prevalence of metabolic syndrome than women with PCOS without OSA.
Role of obstructive sleep apnea in metabolic risk in PCOS
2021, Current Opinion in Endocrine and Metabolic ResearchCitation Excerpt :Hyperandrogenism, a cardinal feature of PCOS [39] can predispose to OSA via effects on neural control of breathing [40] and upper airway mechanics [41]. High androgen levels in PCOS have been associated with increased risk for OSA in some [20,26,42] but not all studies [24]. In addition, low progesterone and low estrogen concentrations can possibly contribute to this risk because low levels might increase frequency of apneic events in women across a broad age spectrum [43,44].
Effect of Prunus dulcis and Salvia hispenica in the management of polycystic ovary syndrome in Wistar rats
2020, Journal of Taibah University Medical SciencesSexual dimorphism of cardiopulmonary regulation in the arcuate nucleus of the hypothalamus
2017, Respiratory Physiology and NeurobiologyCitation Excerpt :This study was conducted using questionnaires to ascertain the level of SDB and daytime sleepiness, however the physiological consequences of SDB were not be determined. To do so another study by a Chatterjee et al., evaluated cardiovascular and metabolic parameters in patients with polycystic ovary disease with (33 patients) and without SDB (17 patients; (Chatterjee et al., 2014). The presence of SDB (using questionnaires and polysomnography studies) indicted a worsening of cardiovascular parameters and metabolic status in these patients.
Obstructive sleep apnea and polycystic ovary syndrome: cause or association?
2017, Sleep MedicineObesity may be the common pathway for sleep-disordered breathing in women with polycystic ovary syndrome
2016, Sleep MedicineCitation Excerpt :Furthermore, this study is a first of its kind in the Indian population who are genetically more susceptible to metabolic disorders leading to formulation of an Indian standardization of normal and abnormal criteria for defining BMI [35]. The presence of more severe metabolic dysfunction in patients of PCOS with SDB as shown by the authors in their previous study [51] makes them especially vulnerable to developing long-term cardiovascular complications. To summarize, we found in this study that SDB was much more prevalent in PCOS patients, which was associated with increased levels of FT. The testosterone levels correlated positively with the RDI and waist circumference.