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Brief Wake Episodes Modulate Sleep-Inhibited Luteinizing Hormone Secretion in the Early Follicular Phase

Reproductive Endocrine Unit (J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; and Neuroendocrine Lab (J.P.S., G.S.R.), Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Janet E. Hall, M.D., Reproductive Endocrine Unit, Bartlett Hall Extension 5, Massachusetts General Hospital, 50 Fruit Street, Boston, Massachusetts 02114. E-mail: jehall{at}partners.org.

To determine the influence of sleep, sleep stage, and time of day on the dynamics of pulsatile LH secretion in the early follicular phase (EFP) of the menstrual cycle, 11 normal women underwent simultaneous polysomnographic monitoring of sleep and measurement of LH in frequent sampling studies during a 40-h protocol that consisted of one night of normal sleep and one night of sleep deprivation followed by an afternoon nap.

The interpulse interval of LH was longer during sleep than wake whether it occurred at night or during the day (P < 0.002), implying a decrease in GnRH pulse frequency associated with sleep in the EFP. LH pulse amplitude was greater during sleep than wake (P < 0.001) and greater pulse amplitudes were associated with longer interpulse intervals during sleep (P < 0.005), but not wake. An interaction between sleep and time of day was observed for mean LH, with lower mean LH levels during sleep than wake at night (P < 0.02), but not during the day.

Wakefulness was more likely to be associated with an LH pulse than were stages I/II, III/IV (slow wave), or rapid eye movement sleep (P < 0.005). In addition, the probability of wakefulness within the sleep episode increased 5–15 min before the onset of LH pulses (relative to randomly selected nonpulse LH; P < 0.05), suggesting that wakefulness was the primary event.

In the absence of sleep, there was an effect of time of day on mean LH (P < 0.02) and LH pulse amplitude (P < 0.03), with greatest values seen during the evening.

In conclusion, in the EFP, inhibition of LH pulse frequency is related to sleep rather than time of day. During periods of sleep, LH pulses occur most commonly in association with brief awakenings, suggesting that interruptions from sleep allow escape from the inhibitory effect of sleep on pulsatile GnRH secretion. A separate effect of time of day on LH pulse dynamics in the absence of sleep was also observed with evening augmentation of LH pulse amplitude and mean level; however, additional studies will be required to determine whether this represents a true circadian effect.

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