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 endtidal 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 endtidal CO2 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.