There is an extensive body of literature indicating that estrogen and progesterone play important regulatory roles in the circadian rhythms of hamsters and rats. However, this area has received little systematic attention in humans. This protocol is designed to study the circadian rhythms of normal women under pharmacologically controlled hormonal conditions. Normal volunteers are treated with Leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist, for three months. This treatment reversibly suppresses endogenous secretion of gonadotropins, estrogen, and progesterone, During one of these months, subjects receive estrogen replacement while they receive progesterone replacement during another month. Thus, subjects can be studied in three pharmacologically controlled hormonal conditions: the hypogonadal state, estrogen alone, and progesterone alone. In each of these conditions, the subjects' circadian rhythms are studied through the use of sleep logs, wrist activity monitors, and rectal temperature monitoring. In addition, during a 48-hour period in each of the conditions, patients are admitted for intensive evaluation that includes frequent blood sampling of prolactin, melatonin, and growth hormone, as well as a constant routine procedure designed to minimize the masking effects of sleep, light, and caloric loading on circadian rhythms. Recruitment of subjects is beginning at this time, so results are not yet available. This line of research is important because of the possible etiologic links between sleep and affective illness, and between gonadal steroids and affective illness. In addition, the protocol may elucidate the effects of hormone replacement therapy on circadian rhythms in normal women.
