title: Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy.
abstract: OBJECTIVE
  Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy (MHT). The mechanisms mediating these effects remain unclear. Orexin A (OxA) is a neuro-peptide that regulates sleep/wakefulness, food intake and metabolism. This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study (KEEPS).
  
  
  METHODS
  KEEPS randomized women within three years of menopause to: oral conjugated equine estrogen (o-CEE, 0.45mg/day), transdermal 17β estradiol (t-E2, 50μg/day), or placebo pills and patches for four years. Plasma OxA levels were measured by enzyme immunoassays in fasting blood samples collected annually from KEEPS participants at Mayo Clinic during and three years after MHT. Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences.
  
  
  RESULTS
  During treatment, OxA levels increased more in women randomized to o-CEE compared with the other groups. Women randomized to either form of MHT demonstrated smaller increases in BMI than those on placebo. Insomnia severity decreased similarly among treatment groups. However, neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels. Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments.
  
  
  CONCLUSIONS
  Although OxA levels increased only in women randomized to o-CEE, these changes did not correlate with changes in sleep quality or BMI. The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17β-estradiol. Clinical Trial Registration for KEEPS: NCT00154180.
authors.affiliation: Mayo Graduate School, Mayo Clinic, Rochester, MN, United States.
authors.forename: Dahima
authors.initials: D
authors.lastname: Cintron
authors.affiliation: Biology Department, St. Olaf College, Northfield, MN, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Beckman
authors.affiliation: Department of Health Sciences Research (Divisions of Biomedical Statistics and Informatics), Mayo Clinic, Rochester, MN, United States; Department of Health Sciences Research (Divisions of Biomedical Statistics and Epidemiology), Mayo Clinic, Rochester, MN, United States.
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.affiliation: Department of Health Sciences Research (Divisions of Biomedical Statistics and Informatics), Mayo Clinic, Rochester, MN, United States; Department of Health Sciences Research (Divisions of Biomedical Statistics and Epidemiology), Mayo Clinic, Rochester, MN, United States.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lahr
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, MN, United States; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States.
authors.forename: Muthuvel
authors.initials: M
authors.lastname: Jayachandran
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, MN, United States; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States. Electronic address: miller.virginia@mayo.edu.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D015992:Body Mass Index; D004734:Energy Metabolism; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004967:Estrogens / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D000068797:Orexins / Q000097:blood*; D012890:Sleep; D057968:Transdermal Patch; D016896:Treatment Outcome; D055105:Waist Circumference
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D000068797:Orexins; D004958:Estradiol
keywords: 17β estradiol; Appetite; Conjugated equine estrogen; Hypocretin; KEEPS; Leptin; Sleep