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

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.