This project is designed to examine sleep and circadian effects on the neuroendocrine dynamics of the reproductive axis. Protocol 290A is designed to deterine: 1) the effects of age and physiologic hormone replacement on the frequency of pulsatile GnRH secretion (as assessed by p ulsatile LH and/or FAS); 2) the effects of hormone replacement on sleep architecture in older and younger PMW; and 3) the interrelationships between sleep and GnRH or LH secrtetion as a function of age. To date, 17 subjects have been completed this complex 3-month protocol. At baseline, subjects were studied at night both asleep and awake. Results indicate that there is a sleep-related decrease in the frequency of pulastile FAS (and, by inference, GnRH) secretion in PMW which is not altered with aging. Further studies will need to address any additional effects of gonadal steroids on this interrelationship between sleep and the GnRH pulse generator. Preliminary analysis indicates that estrogen decreases mean LH, FSH and FAS in PMW in the absence of changes in GnRH pulse frequency while estrogen + progesterone results in further decreases in mean levels and a decrease in GnRH frequency. Sensitivity of sex steroids negative feedback is preserved in older PMW. Protocol 0290B examined the circadian rhythm of LH, FSH and FAS in younger and older PMW. Twenty-two subjects have been studied and results indicatre that there is no circadian rhythm of LH, FSH or FAS in younger or older PMW despite the persistence of normal rhythms of cortisol and TSH. Protocol 290B2 was designed to determine whether true circadian rhythms of LH secretory dynamics occur in women in the early follicular phase as had been suggested by less controlled studies, to begin to address the question of whether reproductive circadian rhythms are lost early or are dependent on the hormonal environment. Twelve studies have been approved for this protocol and 7 studies have been completed.