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

Sleep. 2006 Jan;29(1):95-103. doi: 10.1093/sleep/29.1.95.


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.

MeSH terms

  • Carbon Dioxide / metabolism
  • Estrogens / therapeutic use*
  • Female
  • Hormone Replacement Therapy / methods
  • Humans
  • Male
  • Middle Aged
  • Postmenopause / physiology
  • Progesterone / therapeutic use*
  • Prospective Studies
  • Severity of Illness Index
  • Sleep Apnea, Obstructive / diagnosis*
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep Stages / physiology*


  • Estrogens
  • Carbon Dioxide
  • Progesterone