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J Appl Physiol 94: 101-107, 2003. First published September 13, 2002; doi:10.1152/japplphysiol.00264.2002
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Vol. 94, Issue 1, 101-107, January 2003

Effect of testosterone on the apneic threshold in women during NREM sleep

X. S. Zhou1, J. A. Rowley1, F. Demirovic1, M. P. Diamond2, and M. S. Badr1

1 Sleep Research Laboratory, John D. Dingell Veterans Affairs Medical Center, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, and 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan 48201

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10-12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 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 (%VE) was plotted against the change in end-tidal CO2 (PETCO2); %VE was given a value of zero during central apnea. The AT was defined as the PETCO2 at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression VE vs. PETCO2. Both the AT (39.5 ± 2.9 vs. 42.1 ± 3.0 Torr; P = 0.002) and HPVR (0.20 ± 0.05 vs. 0.33 ± 0.11%VE/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.

control of breathing; hypocapnia; gender


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