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Effect of Testosterone on the Apneic Threshold in Females During NREM Sleep Final Accepted Version

Abstract The hypocapnic apneic threshold (AT) is lower in females relative to males. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during NREM sleep in 8 healthy non-snoring pre-menopausal females before and after 10 to 12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 minutes with tidal volumes ranging from 175-215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%V E ) was plotted against the change in end-tidal CO 2 (P ET CO 2 ); %V E was given a value of zero during central apnea. The AT was defined as the P ET CO 2 at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression V E v. P ET CO 2 . Both the AT (39.5±2.9 mmHg v. 42.1±3.0 mmHg, p=0.002) and HPVR (0.20+0.05 %V