Sex differences in phase angle of entrainment and melatonin amplitude in humans

Abstract

Studies of sex differences in the timing of human circadian rhythms have reported conflicting results. This may be because the studies conducted to date have not controlled for the masking effects of the rest activity cycle on the circadian rhythms being assessed. In the present analysis of data collected under controlled conditions, we examined sex differences in the timing of circadian rhythms while minimizing masking from behavioral and environmental factors using a constant routine (CR) protocol. All participants (28 women and 28 men paired by habitual wake time; age range, 18 30 years) maintained a regular self selected sleep wake schedule at home prior to the study. After 3 baseline days in the laboratory, participants began a CR. Women were found to have a significantly higher melatonin amplitude and lower temperature amplitude than men. While sleep timing was the same between the 2 groups, the timing of the circadian rhythms of core body temperature and pineal melatonin secretion was earlier relative to sleep time in women as compared to men. Sleep therefore occurred at a later biological time for women than men, despite being at the same clock time. Given that sleep propensity and structure vary with circadian phase and are impacted by circulating melatonin, these findings may have important implications for understanding sex differences in sleep timing and duration, diurnal preference, and the prevalence of sleep disorders such as insomnia.

Figure 1

Melatonin waveforms for women and men on CR. Upper panel: Average (± standard error) melatonin waveforms for women (black boxes) and men (open boxes). Plasma melatonin values were averaged per hour beginning at wake time on the CR for each participant. Data for all participants within each group were averaged per hour across the CR. Only those hourly bins in which at least 14 participants remained on CR (hours 0-40) were included. Lower panel: Average proportion of fitted peak melatonin values for women and men. As the normalized peak occurred at different times for each participant, the average waveform for each group has a peak that is less than 1.Vertical lines represents the habitual sleep time (solid line) and habitual wake time (dashed line). HW= Habitual Wake time.

Figure 2

Relative timing of the circadian phase markers with respect to sleep timing in women and men. Open boxes indicate the average timing of the habitual sleep episode in women (upper bar) and men (lower bar). Upward triangle indicates average (± standard error) dim light melatonin onset (DLMOn_25%). Downward triangle indicates average (± standard error) dim light melatonin offset (DLMOff_25%). Circle indicates average (± standard error) core body temperature minimum (CBT_min).