An extensive body of literature indicates that estrogen, progesterone, and testosterone play important regulatory roles in the circadian rhythms of hamsters and rats. However, this area has received little systematic attention in humans. In addition, while sleep disturbance is one of the most common complaints of peri- and post-menopausal women, little is known about the effects of the hypogonadal state, or of hormone replacement, on sleep. This experiment is designed to study the circadian rhythms and sleep of male and female volunteers under pharmacologically controlled hormonal conditions. Normal volunteers are treated with Leuprolide acetate (Lupron), a gonadotropin releasing hormone (GnRH) agonist for two (men or three (women) months. The treatment temporarily suppresses the endogenous secretion of gonadotropins and gonadal steroids. In the course of Lupron treatment, hormone replacement is prescribed so that female subjects can be studies in three hormonal conditions (hypogonadal, estrogen, progesterone), while men can be studied in two (hypogonadal, testosterone). In each of these hormonal conditions, the subjects' circadian rhythms and sleep/wake cycle are studied through the use of sleep logs, wrist activity monitors, and rectal temperature monitors. In addition, during a 48-hour period in each of the conditions, subjects are admitted for intensive evaluation that includes a night of EEG-monitored sleep and a 24-hour constant routine procedure. The constant routine procedure is designed to minimize the masking effects of sleep, light, and caloric loading on circadian rhythms. During this procedure, blood samples are drawn for the measurement of TSH and melatonin. Ten men and five women have completed the study. Data analysis for the men is now being formed; more subjects are being recruited for the female study. Preliminary analysis of the male melatonin data shows no difference in the timing, duration, or amplitude of nocturnal melatonin secretion in the hypogonadal vs. the testosterone replacement conditions. There is, however, a trend (p=.07) for the duration of the nocturnal temperature trough to be prolonged in the hypogonadal state. Self- recorded sleep logs show no difference in sleep duration or in the times of sleep onset and offset between the two hormonal conditions. However, EEG recordings show a significant decrease in the amount of stage 4 sleep in the hypogonadal state (p=.05), as well as trends toward an increase in the amount of stage 3 sleep (p=.08) and a decrease in REM latency (p=.09). These data indicate that, while testosterone does not appear to regulate circadian rhythms in humans, it may play a role in sleep regulation.
