Obstructive sleep apnea is a disorder with a strong male predominance. One possible explanation could be an effect of female hormones on pharyngeal dilator muscle activity. Therefore, we determined the level of awake genioglossus electromyogram (EMGgg) and upper airway resistance in 12 pre- and 12 postmenopausal women under basal conditions and during the application of an inspiratory resistive load (25 cmH2O . l-1 . s). In addition, a subgroup of eight postmenopausal women were studied a second time after 2 wk of combined estrogen and progesterone replacement in standard doses. Peak phasic and tonic genioglossus activity, expressed as a percentage of maximum, were highest in the luteal phase of the menstrual cycle (phasic 23.9 +/- 3.8%, tonic 10.2 +/- 1.0%), followed by the follicular phase (phasic 15.5 +/- 2.2%, tonic 7.3 +/- 0.8%), and were lowest in the postmenopausal group (phasic 11.3 +/- 1.6%, tonic of 5.0 +/- 0.6), whereas upper airway resistance did not differ. There was a weak but significant positive correlation between progesterone levels and both peak phasic (P < 0.05) and tonic (P < 0.01) EMGgg. Finally, there was a significant increase in EMGgg in the postmenopausal group restudied after hormone therapy. In conclusion, female hormones (possibly progesterone) have a substantial impact on upper airway dilator muscle activity.