The determinants of the apnea threshold during NREM sleep in normal subjects

James A. Rowley, Xusong S. Zhou, Michael P. Diamond, M. Safwan Badr

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Study Objective: To determine whether (1) postmenopausal women have a higher apnea threshold than premenopausal women and men and (2) hormone replacement therapy would decrease the apnea threshold in postmenopausal women. Design: Protocol #1: Analysis of a prospectively collected database of 55 subjects who had undergone an apnea-threshold protocol. Protocol #2: Intervention study: apnea threshold compared in 6 postmenopausal women before and after 30 days of replacement therapy with progestin and estrogen. Setting: Research sleep laboratory. Participants: Healthy volunteers aged 18 to 65 years without evidence of sleep-disordered breathing. Interventions: Hypocapnia was induced via nasal mechanical ventilation for 3 minutes during stable non-rapid eye movement sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending upon the magnitude of the hypocapnia. The change in end-tidal CO2 at the apnea threshold was defined as the change in end-tidal CO2 associated with the apnea closest to the last hypopnea. Measurements and Results: The change in the end-tidal CO2 at the apnea threshold was highest in the premenopausal women (4.6±0.6 mm Hg), with no difference between the postmenopausal women (3.1±0.5 mm Hg) and men (3.4±0.7 mm Hg). Determinants of the change in end-tidal CO 2 at the apnea threshold included sex and menopause status. Hormone replacement therapy increased the change in end-tidal CO2 at the apnea threshold from 2.9±0.4 mm Hg to 4.8±0.4 mm Hg (P<.001). Conclusions: These data support the hypothesis that estrogens and progestins positively influence the apnea threshold and control of breathing during non-rapid eye movement sleep.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
Issue number1
StatePublished - Jan 1 2006
Externally publishedYes


  • Aging
  • Body mass index
  • Control of breathing
  • Hypocapnia
  • Upper airway resistance

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)


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