Gender and obstructive sleep apnea syndrome, part 2: mechanisms.

Epidemiologic studies have reported that obstructive sleep apnea syndrome (OSAS) is a common disorder affecting about four percent of adult males and two percent of adult females. This difference in OSAS prevalence suggests that the female gender may reduce the risk of sleep breathing disorders in adults. We review several interrelated factors that may explain the differences in risk related to gender. These include differences in obesity and the distribution of adipose tissue, upper-airway anatomy, upper-airway muscle function, control of ventilation, the effect of sex hormones and leptin. The gender related protective effect decreases in females who are postmenopausal and not on hormone replacement therapy.

[1]  R. Grunstein,et al.  Association of serum leptin with hypoventilation in human obesity , 2002, Thorax.

[2]  E. Bixler,et al.  Prevalence of sleep-disordered breathing in women: effects of gender. , 2001, American journal of respiratory and critical care medicine.

[3]  J. Stradling,et al.  Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. , 1991, Thorax.

[4]  N. Collop,et al.  The upper airway resistance syndrome. , 1999, Chest.

[5]  A. Malhotra,et al.  Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome. , 2001, The Journal of clinical endocrinology and metabolism.

[6]  A. J. Block,et al.  Sleep-disordered breathing and oxygen desaturation in obese patients. , 1981, Chest.

[7]  J. Weil,et al.  Progesterone for outpatient treatment of Pickwickian syndrome. , 1975, Annals of internal medicine.

[8]  C. Shapiro,et al.  Breathing and oxygenation during sleep are similar in normal men and normal women. , 1985, The American review of respiratory disease.

[9]  T. Rabben,et al.  Sleep apnoea syndrome treated with oestradiol and cyclic medroxyprogesterone , 1991, The Lancet.

[10]  L. Melton,et al.  Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women. , 2000, Metabolism: clinical and experimental.

[11]  W. Cook,et al.  Indices of severity of obstructive sleep apnea syndrome do not change during medroxyprogesterone acetate therapy. , 1989, Chest.

[12]  R. Schwab.  Sex differences and sleep apnoea , 1999, Thorax.

[13]  C. O'Donnell,et al.  Upper airway collapsibility: the importance of gender and adiposity. , 2000, American journal of respiratory and critical care medicine.

[14]  C. Dulberg,et al.  A comparison of men and women with occlusive sleep apnea syndrome. , 1988, Chest.

[15]  P. L. Smith,et al.  Leptin, obesity, and respiratory function. , 2000, Respiration physiology.

[16]  B. Jabbari,et al.  Effects of medroxyprogesterone acetate in obstructive sleep apnea. , 1986, Chest.

[17]  K. Strohl,et al.  Size and mechanical properties of the pharynx in healthy men and women. , 1992, The American review of respiratory disease.

[18]  J. Weil,et al.  Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome. , 1975, The American journal of medicine.

[19]  M. Legato,et al.  Gender-specific aspects of obesity. , 1997, International journal of fertility and women's medicine.

[20]  D. White,et al.  Influence of gender on waking genioglossal electromyogram and upper airway resistance. , 1995, American journal of respiratory and critical care medicine.

[21]  P. Cistulli,et al.  Effect of testosterone administration on upper airway collapsibility during sleep. , 1994, American journal of respiratory and critical care medicine.

[22]  J. Appelberg,et al.  Ventilatory response to CO2 in patients with snoring, obstructive hypopnoea and obstructive apnoea. , 1997, Clinical physiology.

[23]  L. Moore,et al.  Combined effects of female hormones and metabolic rate on ventilatory drives in women , 1989 .

[24]  P. L. Smith,et al.  Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. , 1991, The American review of respiratory disease.

[25]  N J Douglas,et al.  Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects. , 1998, American journal of respiratory and critical care medicine.

[26]  A. Bachour,et al.  Sleep-related disordered breathing during pregnancy in obese women. , 2001, Chest.

[27]  W. C. Ball,et al.  Topics in clinical medicine: serious complications and sudden death in the Pickwickian syndrome. , 1970, The Johns Hopkins medical journal.

[28]  K. Flegal,et al.  Increasing Prevalence of Overweight Among US Adults: The National Health and Nutrition Examination Surveys, 1960 to 1991 , 1994 .

[29]  A. Malhotra,et al.  Upper airway muscle responsiveness to rising PCO(2) during NREM sleep. , 2000, Journal of applied physiology.

[30]  J. Després,et al.  Obesity in Canada: a descriptive analysis. Canadian Heart Health Surveys Research Group. , 1997, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[31]  K. Lam,et al.  Serum leptin and vascular risk factors in obstructive sleep apnea. , 2000, Chest.

[32]  J. Weil,et al.  Impaired oxygenation during sleep in excessive polycythemia of high altitude: improvement with respiratory stimulation. , 1978, Sleep.

[33]  R. Millman,et al.  Body fat distribution and sleep apnea severity in women. , 1995, Chest.

[34]  P. Cistulli,et al.  Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women. , 1994, Thorax.

[35]  D. White,et al.  Influence of testosterone on breathing during sleep. , 1986, Journal of applied physiology.

[36]  Ian Marshall,et al.  Neck soft tissue and fat distribution: comparison between normal men and women by magnetic resonance imaging , 1999, Thorax.

[37]  A. Malhotra,et al.  Airway mechanics and ventilation in response to resistive loading during sleep: influence of gender. , 2000, American journal of respiratory and critical care medicine.

[38]  Daniel J Buysse,et al.  Sleep–Related Breathing Disorders in Adults: Recommendations for Syndrome Definition and Measurement Techniques in Clinical Research , 2000 .

[39]  D. White,et al.  Upper airway muscle activity in normal women: influence of hormonal status. , 1998, Journal of applied physiology.

[40]  D. White,et al.  Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. , 1996, American journal of respiratory and critical care medicine.

[41]  A. R. Frisancho.  Anthropometric Standards for the Assessment of Growth and Nutritional Status , 1990 .

[42]  N. Zamel,et al.  Pharyngeal cross-sectional area in normal men and women. , 1986, Journal of applied physiology.

[43]  J. Shepard,et al.  Localization of upper airway collapse during sleep in patients with obstructive sleep apnea. , 1990, The American review of respiratory disease.

[44]  D. Bliwise.  Do patients with obstructive sleep apnea have thick necks? , 1991, The American review of respiratory disease.

[45]  J. Remmers,et al.  Induction of the obstructive sleep apnea syndrome in a woman by exogenous androgen administration. , 1984, The American review of respiratory disease.

[46]  D. White,et al.  Hypoxic ventilatory response during sleep in normal premenopausal women. , 2015, The American review of respiratory disease.

[47]  L. Moore,et al.  Increased HVR in pregnancy: relationship to hormonal and metabolic changes. , 1987, Journal of applied physiology.

[48]  P. Hanly,et al.  Impact of menopause on the prevalence and severity of sleep apnea. , 2001, Chest.

[49]  Progressive changes in airway resistance during sleep. , 1996, Journal of applied physiology.

[50]  D. White,et al.  Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). , 1992, The Journal of clinical investigation.

[51]  A. Malhotra,et al.  Genioglossal activation in patients with obstructive sleep apnea versus control subjects. Mechanisms of muscle control. , 2001, American journal of respiratory and critical care medicine.

[52]  E. Onal,et al.  Diaphragmatic and genioglossal electromyogram responses to CO2 rebreathing in humans. , 1981, Journal of applied physiology: respiratory, environmental and exercise physiology.

[53]  J. Després,et al.  Obesity in Canada: a descriptive analysis. Canadian Heart Health Surveys Research Group. , 1997, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[54]  A I Pack,et al.  Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. , 1995, American journal of respiratory and critical care medicine.

[55]  N J Douglas,et al.  Influence of age and gender on upper airway resistance in NREM and REM sleep. , 2001, Journal of applied physiology.

[56]  C. Guilleminault,et al.  Upper airway resistance syndrome is a distinct syndrome. , 2000, American journal of respiratory and critical care medicine.

[57]  J. Rowley,et al.  Influence of gender on upper airway mechanics: upper airway resistance and Pcrit. , 2001, Journal of applied physiology.

[58]  D. Keefe,et al.  Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study. , 1999, Menopause.

[59]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[60]  V. Hoffstein,et al.  Lung volume-related changes in the pharyngeal area of obese females with and without obstructive sleep apnoea. , 1989, The European respiratory journal.

[61]  R. Mcevoy,et al.  Ventilatory decline after hypoxia and hypercapnia is not different between healthy young men and women. , 2000, Journal of applied physiology.

[62]  D. Rapoport,et al.  Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep. , 2001, Chest.

[63]  B. Ferguson.  Pharyngeal fat in obstructive sleep apnea , 1994 .

[64]  A. Jordan,et al.  Genioglossus muscle activity at rest and in response to brief hypoxia in healthy men and women. , 2002 .

[65]  M. Badr,et al.  Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep. , 2000, Journal of applied physiology.

[66]  A. Grassino,et al.  Load compensation in obese patients during quiet tidal breathing. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[67]  Y. Honda,et al.  Analysis of pressure profile in the occluded airway obtained at the beginning of inspiration in steady state hypercapnia. , 1981, The American review of respiratory disease.

[68]  Kathryn A. Lee,et al.  TESTOSTERONE REPLACEMENT IN HYPOGONADAL MEN: EFFECTS ON OBSTRUCTIVE SLEEP APNOEA, RESPIRATORY DRIVES, AND SLEEP , 1985, Clinical endocrinology.

[69]  E. Sforza,et al.  Upper airway collapsibility and cephalometric variables in patients with obstructive sleep apnea. , 2000, American journal of respiratory and critical care medicine.

[70]  D. White,et al.  Influence of testosterone on ventilation and chemosensitivity in male subjects. , 1985, Journal of applied physiology.

[71]  P. L. Smith,et al.  Female gender exacerbates respiratory depression in leptin-deficient obesity. , 2001, American journal of respiratory and critical care medicine.

[72]  Daniel J Buysse,et al.  Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. , 1999, Sleep.

[73]  J. Després,et al.  Correlation between cardiovascular disease risk factors and simple anthropometric measures. Canadian Heart Health Surveys Research Group. , 1997, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[74]  P. Hanly,et al.  Gender differences in the polysomnographic features of obstructive sleep apnea. , 2000, American journal of respiratory and critical care medicine.

[75]  M Partinen,et al.  Women and the obstructive sleep apnea syndrome. , 1988, Chest.

[76]  B. Blanksby,et al.  CO2 sensitivity changes during the menstrual cycle. , 1989, Journal of applied physiology.

[77]  D. White,et al.  Hypercapnic ventilatory response in sleeping adults. , 2015, The American review of respiratory disease.

[78]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[79]  E D Robin,et al.  Extreme obesity associated with alveolar hypoventilation--a Pickwickian Syndrome. 1956. , 1956, Obesity research.

[80]  D. White,et al.  Sexual influence on the control of breathing. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[81]  J. Manfreda,et al.  The use of health-care resources in obesity-hypoventilation syndrome. , 2001, Chest.

[82]  J. Trinder,et al.  Gender differences in airway resistance during sleep. , 1997, Journal of applied physiology.

[83]  L. Moore,et al.  Progestin and estrogen reduce sleep-disordered breathing in postmenopausal women. , 1989, Journal of applied physiology.

[84]  M. Kryger,et al.  Breathing during sleep in normal pregnant women. , 1986, The American review of respiratory disease.

[85]  J. Weil,et al.  Effects of progesterone on chemosensitivity in normal men. , 1978, The Journal of laboratory and clinical medicine.

[86]  V. Somers,et al.  Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea. , 2000, American journal of physiology. Heart and circulatory physiology.

[87]  M. Kryger,et al.  Gender and obstructive sleep apnea syndrome, part 1: Clinical features. , 2002, Sleep.

[88]  A A Lowe,et al.  The relationship between obesity and craniofacial structure in obstructive sleep apnea. , 1995, Chest.

[89]  J. A. Scott,et al.  Influence of sex and age on duration and frequency of sleep apnea events. , 2000, Sleep.

[90]  J. Skatrud,et al.  Effect of induced hypocapnic hypopnea on upper airway patency in humans during NREM sleep. , 1997, Respiration physiology.

[91]  H. Kimura,et al.  Sex differences in awake ventilatory drive and abnormal breathing during sleep in eucapnic obesity. , 1988, Chest.

[92]  A. Miller,et al.  In-hospital mortality in the Pickwickian syndrome. , 1974, The American journal of medicine.

[93]  V. Mohsenin,et al.  Gender differences in the expression of sleep-disordered breathing : role of upper airway dimensions. , 2001, Chest.

[94]  G. Man,et al.  Hypercapnic ventilatory response in patients with and without obstructive sleep apnea: do age, gender, obesity, and daytime PaCO(2) matter? , 2000, Chest.

[95]  D. White,et al.  Pharyngeal resistance in normal humans: influence of gender, age, and obesity. , 1985, Journal of applied physiology.

[96]  P. L. Smith,et al.  Leptin prevents respiratory depression in obesity. , 1999, American journal of respiratory and critical care medicine.

[97]  R. Chervin,et al.  Upper Airway Sleep-Disordered Breathing in Women , 1995, Annals of Internal Medicine.

[98]  L. Findley,et al.  Oxyhemoglobin saturation during sleep in subjects with and without the obesity-hypoventilation syndrome. , 1985, Chest.