Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep

John D. Dingell Veterans Affairs Medical Center, and Division of Pulmonary and Critical Care Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Journal of Applied Physiology (Impact Factor: 3.06). 08/2000; 89(1):192-9.
Source: PubMed


We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25-35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21-43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (VT) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal PCO(2) (PET(CO(2))) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in VT to 155 +/- 29% (mean +/- SD) and a reduction of PET(CO(2)) by -4.72 +/- 0.57 Torr. In men, induction of a central apnea required an increase in VT to 142 +/- 13% and a reduction of PET(CO(2)) by -3.54 +/- 0.31 Torr (P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.

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Available from: Mark Babcock, Dec 15, 2015
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    • "The prevalence of obstructive sleep apnea (OSA) is more than three times greater in men than in women (Bixler et al., 2001; Young et al., 1993). The underlying phenotypical basis for this discrepancy is not well understood, although a number of broad gender-influenced physiological characteristics have been implicated, including: (1) obesity and fat distribution (Simpson et al., 2010), (2) upper airway anatomy and function (Brooks and Strohl, 1992; Mohsenin, 2001; Pillar et al., 2000), (3) ventilatory control (Jordan et al., 2005; Pillar et al., 2000), (4) hormonal status (Zhou et al., 2000) and (5) craniofacial anatomy (Lee et al., 1997). Some authors have invoked specific gender-based anatomical differences, including: (1) a longer and consequently more collapsible pharyngeal airway in men and (2) differences in mandible position (Malhotra et al., 2002; Mohsenin, 2003). "
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    ABSTRACT: Obstructive sleep apnea (OSA) is more common in men than women. Body size is greater in males (sexual dimorphism), but large body habitus is associated with OSA for both genders. We speculated that male–female phenotypical convergence (reduced sexual dimorphism via identical phenotype acquisition) occurs with OSA and tested hypotheses: (1) phenotypical features pathogenic for OSA differ between OSA and healthy subjects irrespective of gender; and (2) such characteristics exhibit phenotypical convergence. Utilizing an existing database, we calculated male–female (group average) ratios for eight anthropometric and 33 surface cephalometric variables from 104 Caucasian OSA patients [72 males; apnea–hypopnea index (events h−1): males: 42.3 ± 24.7 versus females: 42.6 ± 26.1 (P > 0.9)] and 85 Caucasian, healthy, non-OSA, community volunteers (36 males). Log-transformed data were analysed using a general linear model with post-hoc unpaired t-tests and significance at P < 0.0012 (Bonferroni multiple-comparison correction). OSA patients were older (56.9 ± 14.4 versus 38.0 ± 13.8 years), but there were no within-group gender-based age differences. All anthropometric variables (except height), plus cranial base width, mandibular breadth and retromandibular width diagonal were larger in gender-matched OSA versus healthy comparisons; thus satisfying hypothesis (1). Male–female ratios were mostly >1.0 across groups, but with no significant group × gender interactions no variable satisfied hypothesis (2). Thus, in this exploratory study, OSA patients had gender-common phenotypical differences to healthy subjects, but sexual dimorphism was preserved. Lack of complete phenotypical convergence may indicate gender-based critical phenotype-level attainment for OSA and/or gender-based OSA prevalence arises from factors other than those in this study.
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    • "If carbon dioxide levels are beneath the chemoreflex threshold, central respiratory drive and chest wall respiratory muscle activity are eliminated culminating in a central apnea. The carbon dioxide level that demarcates the point at which ventilation is abolished has been deemed the apneic threshold (Dempsey, 2005; Xie et al., 2002; Zhou et al., 2000). The absence of central drive is also coupled to a reduction in upper airway muscle activity and ultimately to partial or complete closure of the upper airway (Badr et al., 1995, 1997; Badr and Kawak, 1996). "
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    • "Behan and Wenninger (2008) showed that estrogens, progesterone and testosterone are involved in the central neural control of breathing, affecting cyclic fluctuations in ventilation during normal menstrual cycle. Additional evidence supporting the occurrence of gender-related differences in these respiratory patterns comes from studies that addressed differences between male and female subjects in the apneic threshold, carbon dioxide reserve and hypocapnic ventilatory response (Zhou et al., 2000), although these data are still controversial (Rowley et al., 2001, 2002; Tarbichi et al., 2003). At present, however, no study of acceptable size is available on gender-related differences in sleep-induced PB during exposure to high and very high altitude. "
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