title: A gonadotropin-releasing hormone agonist model demonstrates that nocturnal hot flashes interrupt objective sleep.
abstract: OBJECTIVE
  Sleep interruption is often reported by women with hot flashes and night sweats (or vasomotor symptoms, VMS). Although women report that VMS awaken them, polysomnography (PSG) studies have not consistently supported this contention.
  
  
  METHODS
  We mimicked menopause using a gonadotropin-releasing hormone agonist (GnRHa) to investigate whether VMS increase awakenings and wake after sleep onset (WASO). VMS, serum estradiol, and at-home PSGs (two pretreatment, two posttreatment) were measured before and after 4 weeks on GnRHa. Regression models were used to determine the effect of increasing VMS frequency on awakenings and WASO, as measured objectively and subjectively.
  
  
  METHODS
  Twenty-nine healthy women (mean 27.3 y).
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Depot GnRHa (leuprolide 3.75-mg).
  
  
  RESULTS
  Serum estradiol was rapidly and uniformly suppressed on GnRHa. Persistent VMS were reported by 69% of women. The number of nighttime VMS correlated directly with the degree of sleep disturbance. Each additional reported nighttime VMS was associated with a 62% increase from baseline in PSG-measured WASO (P = 0.007), a 3% increase in awakenings (P = 0.05), and 6% increase in %N1 sleep (P = 0.02). Nighttime VMS were also associated with increased perceived WASO (312%; P = 0.02), awakenings (16%; P = 0.007), Insomnia Severity Index (P = 0.03), and Pittsburgh Sleep Quality Index (P = 0.03) scores, and decreased perceived sleep efficiency (P = 0.01). Objectively recorded nighttime VMS correlated with PSG-measured WASO (rs = 0.45, P = 0.02).
  
  
  CONCLUSIONS
  This menopause model demonstrates that nighttime vasomotor symptoms correlate with increased sleep fragmentation. These findings are consistent with a specific contribution of vasomotor symptoms to polysomnography-measured sleep interruption suggesting that nighttime vasomotor symptoms interrupt sleep in the setting of menopause.
authors.affiliation: Women's Hormones and Aging Research Program, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA ; Department of Psychosocial Oncology and Palliative Care Medicine, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA ; Center for Women's Mental Health, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Hadine
authors.initials: H
authors.lastname: Joffe
authors.forename: Sybil
authors.initials: S
authors.lastname: Crawford
authors.forename: Nicole
authors.initials: N
authors.lastname: Economou
authors.forename: Semmie
authors.initials: S
authors.lastname: Kim
authors.forename: Susan
authors.initials: S
authors.lastname: Regan
authors.forename: Janet E
authors.initials: JE
authors.lastname: Hall
authors.forename: David
authors.initials: D
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D019584:Hot Flashes / Q000150:complications*; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012893:Sleep Wake Disorders / Q000209:etiology*; D055815:Young Adult
chemical_list: D004970:Estrone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide
keywords: Menopause; awakenings; hot flashes; polysomnography; wake time after sleep onset