Elsevier

Sleep Medicine

Volume 15, Issue 12, December 2014, Pages 1547-1553
Sleep Medicine

Original Article
Impact of sleep-disordered breathing on metabolic dysfunctions in patients with polycystic ovary syndrome

https://doi.org/10.1016/j.sleep.2014.06.023Get rights and content

Highlights

  • There is a strong association between polycystic ovary syndrome (PCOS) and sleep-disordered breathing (SDB).

  • The metabolic abnormalities in PCOS correlate with the severity of SDB.

  • PCOS patients with SDB have more severe features of hyperandrogenism.

  • PCOS patients with metabolic dysfunctions and hirsutism should be screened for SDB.

Abstract

Background

Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder among women in the reproductive age group. These women are prone to develop sleep-disordered breathing (SDB) and metabolic disorders. SDB is also associated with metabolic dysfunctions. We hypothesized that SDB is an independent risk factor contributing to metabolic dysfunctions in women with PCOS.

Methods

Prospective cross-sectional study in which 50 women with PCOS and not on any treatment were selected. They were divided into two groups: Group 1 - PCOS with SDB and Group 2 - PCOS without SDB.

Results

Thirty-three (66%) women with PCOS had SDB. Women in Group 1 had significantly higher systolic blood pressure (SBP) (P = 0.002); diastolic blood pressure (DBP) (P = 0.044); fasting blood sugar (P = 0.006), triglyceride levels (P = 0.014) and mean Ferriman-Gallwey score (P = 0.028). The HDL was significantly lower in group 1 (P = 0.006). In group 1, 42.4% of women had metabolic syndrome (P < 0.001). Excessive daytime sleepiness (EDS) was significantly higher in Group 1 (P = 0.04). Respiratory distress index significantly correlated positively with waist circumference (r = 0.551, P < 0.001), SBP (r = 0.455, P = 0.001), DBP (r = 0.387, P = 0.006), FBS (r = 0.524, P = 0.000), homeostatic model assessment (r = 0.512, P = 0.000), triglycerides (r = 0.384, P = 0.006), free testosterone (r = 0.390, P = 0.005), and negatively with HDL (r = –0.555, P < 0.001).

Conclusion

Women with PCOS and SDB had significantly increased metabolic abnormalities as well as more severe hyperandrogenism. Women with PCOS who have metabolic abnormalities or severe hyperandrogenism should undergo an overnight PSG.

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.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

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)

  • TasaliE. et al.

    Polycystic ovary syndrome and obstructive sleep apnea

    Sleep Med Clin

    (2008)
  • HuangA. et al.

    Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institute of Health 1990 criteria

    Fertil Steril

    (2010)
  • EhrmannD.A.

    Medical progress: polycystic ovary syndrome

    N Engl J Med

    (2005)
  • FranksS.

    Polycystic ovary syndrome

    N Engl J Med

    (1995)
  • GuzickD.S.

    Polycystic ovary syndrome

    Obstet Gynecol

    (2004)
  • LegroR.S.

    Diagnostic criteria in polycystic ovary syndrome

    Semin Reprod Med

    (2003)
  • Forrester-DumontK. et al.

    Hyperandrogenism does not influence metabolic parameters in adolescent girls with PCOS

    Int J Endocrinol

    (2012)
  • VgontzasA.N. et al.

    Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance

    J Clin Endocrinol Metab

    (2001)
  • NestlerJ.E. 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)
  • Diamanti-KandarakisE. et al.

    A survey of the polycystic ovary syndrome in the Greek Island of Lesbos: hormonal and metabolic profile

    J Clin Endocrinol Metab

    (1999)
  • DunaifA.

    Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus

    Am J Med

    (1995)
  • EhrmannD.A. et al.

    Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome

    Diabetes Care

    (1999)
  • LegroR.S. et al.

    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

    (1999)
  • ReavenG.M.

    Banting lecture 1988: role of insulin resistance in human disease

    Diabetes

    (1988)
  • ReavenG.M.

    Insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension: parallels between human disease and rodent models

    Diabetes Care

    (1991)
  • ZavaroniI. et al.

    Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance

    N Engl J Med

    (1989)
  • American Academy of Sleep Medicine

    International classification of sleep disorders: diagnostic and coding manual

    (2005)
  • YoungT. et al.

    The occurrence of sleep-disordered breathing among middle aged adults

    N Engl J Med

    (1993)
  • KimJ. et al.

    Prevalence of sleep disordered breathing in middle aged Korean men and women

    Am J Respir Crit Care Med

    (2004)
  • ShinoharaE. et al.

    Visceral fat accumulation as an important risk factor for obstructive sleep apnoea syndrome in obese subjects

    J Intern Med

    (1997)
  • LiuK. et al.

    Sleep apnea and neuroendocrine function

    Sleep Med Clin

    (2007)
  • BixlerE.O. et al.

    Prevalence of sleep disordered breathing in women: effects of gender

    Am J Respir Crit Care Med

    (2001)
  • PeppardP.E. et al.

    Prospective study of the association of sleep disordered breathing and hypertension

    N Engl J Med

    (2000)
  • RedlineS. et al.

    Obstructive sleep apnea–hypopnea and incident stroke: the Sleep Heart Health Study

    Am J Respir Crit Care Med

    (2010)
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