Endogenous Circadian Regulation of Female Reproductive Hormones

Context: Studies suggest that female reproductive hormones are under circadian regulation, although methodological differences have led to inconsistent findings. Objective: To determine whether circulating levels of reproductive hormones exhibit circadian rhythms. Design: Blood samples were collected across ∼90 consecutive hours, including 2 baseline days under a standard sleep-wake schedule and ∼50 hours of extended wake under constant routine (CR) conditions. Setting: Intensive Physiological Monitoring Unit, Brigham and Women's Hospital. Participants: Seventeen healthy premenopausal women (22.8 ± 2.6 years; nine follicular; eight luteal). Interventions: Fifty-hour CR. Main Outcome Measures: Plasma estradiol (E2), progesterone (P4), LH, FSH, SHBG, melatonin, and core body temperature. Results: All hormones exhibited significant 24-hour rhythms under both standard sleep-wake and CR conditions during the follicular phase (P < 0.05). In contrast, only FSH and SHBG were significantly rhythmic during the luteal phase. Rhythm acrophases and amplitudes were similar between standard sleep-wake and CR conditions. The acrophase occurred in the morning for P4; in the afternoon for FSH, LH, and SHBG; and during the night for E2. Conclusions: Our results confirm previous reports of ∼24-hour rhythms in many female reproductive hormones in humans under ambulatory conditions but demonstrate that these hormones are under endogenous circadian regulation, defined as persisting in the absence of external time cues. These results may have important implications for the effects of circadian disruption on reproductive function.