Sex difference in the near-24-hour intrinsic period of the human circadian timing system - PubMed

Abstract

The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18-74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.

Conflict of interest statement

Conflict of interest statement: The authors declare a conflict of interest. The following authors declare no conflicts of interest: J.F.D., S.W.C., A.-M.C., A.J.K.P., M.Y.M., C.G., and D.-J.D. K.P.W. reports that he is a consultant for Takeda, Cephalon, and Zeo; he is the Chair of the Scientific Advisory Board and a stockholder in Zeo. J.K.W. reports that he has received investigator-initiated research funding from Respironics on a topic unrelated to the present paper. C.A.C. reports that he has received consulting fees from or served as a paid member of scientific advisory boards for Actelion, Ltd.; Bombardier, Inc.; the Boston Celtics; Cephalon, Inc.; Delta Airlines; Eli Lilly and Co.; Garda Síochána Inspectorate; Global Ground Support; Johnson & Johnson; Koninklijke Philips Electronics, NV; the Minnesota Timberwolves; the Portland Trail Blazers; Philips Respironics, Inc.; Sanofi–Aventis, Inc.; Sepracor, Inc.; Sleep Multimedia, Inc.; Somnus Therapeutics, Inc.; Vanda Pharmaceuticals, Inc.; and Zeo, Inc. He also owns an equity interest in Lifetrac, Inc.; Somnus Therapeutics, Inc.; Vanda Pharmaceuticals, Inc.; and Zeo, Inc., and he has received royalties from McGraw–Hill, the Massachusetts Medical Society/New England Journal of Medicine, the New York Times, Penguin Press, and Philips Respironics. He has received lecture fees from the Alliance for Epilepsy Research; American Academy of Sleep Medicine; Duke University School of Medicine; Mount Sinai School of Medicine; National Academy of Sciences; North East Sleep Society; Sanofi–Aventis, Inc.; Society for Obstetric Anesthesia and Perinatology; St. Luke's Roosevelt Hospital; University of Virginia Medical Center; University of Washington Medical Center; and University of Wisconsin Medical School. He has also received research prizes with monetary awards from the American Academy of Sleep Medicine and the New England College of Occupational and Environmental Medicine; clinical trial research contracts from Cephalon, Inc.; and an investigator-initiated research grant from Cephalon, Inc. His research laboratory at the Brigham and Women's Hospital has received unrestricted research and education funds and/or support for research expenses from Cephalon, Inc.; Koninklijke Philips Electronics, NV; ResMed; and the Brigham and Women's Hospital. The Harvard Medical School Division of Sleep Medicine, which C.A.C. directs, has received unrestricted research and educational gifts and endowment funds from Boehringer Ingelheim Pharmaceuticals, Inc.; Cephalon, Inc.; George H. Kidder, Esq.; Gerald McGinnis; GlaxoSmithKline; Jazz Pharmaceuticals; Lilly USA; Merck & Co., Inc.; Peter C. Farrell, PhD; Pfizer; Praxair US Homecare; ResMed; Respironics, Inc.; Sanofi–Aventis, Inc.; Select Comfort Corporation; Sepracor, Inc.; Sleep Health Centers, LLC; Somaxon Pharmaceuticals; Takeda Pharmaceuticals; Tempur-Pedic; Watermark Medical; and Zeo, Inc. The Harvard Medical School Division of Sleep Medicine Sleep and Health Education Program has received educational grant funding from Cephalon, Inc.; Takeda Pharmaceuticals; Sanofi–Aventis, Inc.; and Sepracor, Inc. C.A.C. is the incumbent of an endowed professorship provided to Harvard University by Cephalon, Inc., and holds a number of process patents in the field of sleep and/or circadian rhythms (e.g., photic resetting of the human circadian pacemaker). Since 1985, he has also served as an expert witness on various legal cases related to sleep and/or circadian rhythms.

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