title: Menopausal hormone therapy and sleep-disordered breathing: evidence for a healthy user bias.
abstract: OBJECTIVE
  Observational studies suggest that menopausal hormone therapy protects against sleep-disordered breathing, but such findings may be biased by a "healthy user effect." When the Women's Health Initiative Study reported in 2002 that estrogen-progestin therapy increases heart disease risk, many women discontinued hormone therapy. We investigate healthy user bias in the association of hormone therapy with sleep-disordered breathing in the Sleep in Midlife Women Study.
  
  
  METHODS
  A total of 228 women aged 38 to 62 years were recruited from the Wisconsin Sleep Cohort Study. They underwent polysomnography to measure apnea-hypopnea index, at home semiannually from 1997 to 2006, and in the sleep laboratory every four years (n = 1828 studies). Hormone therapy was recorded monthly. Linear models with empirical standard errors regressed logarithm of apnea-hypopnea index on hormone use with a pre- or post-July 2002 interaction, adjusting for menopause and age.
  
  
  RESULTS
  The association of hormone therapy and sleep-disordered breathing was heterogeneous (P < .01); apnea-hypopnea index among users was 15% lower in the early period (95% confidence interval, -27% to -1%), but similar to nonusers in the late.
  
  
  CONCLUSIONS
  Hormone therapy was negatively associated with sleep-disordered breathing only until the Women's Health Initiative results were publicized. Hormone therapy may have been a marker for healthfulness in the early period, creating a spurious association with sleep-disordered breathing.
authors.affiliation: Department of Population Health Sciences, University of Wisconsin-Madison, Madison. Electronic address: amirer@wisc.edu.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Mirer
authors.affiliation: Department of Population Health Sciences, University of Wisconsin-Madison, Madison.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Peppard
authors.affiliation: Department of Population Health Sciences, University of Wisconsin-Madison, Madison.
authors.forename: Mari
authors.initials: M
authors.lastname: Palta
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Benca
authors.affiliation: Department of Population Health Sciences, University of Wisconsin-Madison, Madison.
authors.forename: Amanda
authors.initials: A
authors.lastname: Rasmuson
authors.affiliation: Department of Population Health Sciences, University of Wisconsin-Madison, Madison.
authors.forename: Terry
authors.initials: T
authors.lastname: Young
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology; D015982:Bias; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D020249:Hormone Replacement Therapy / Q000706:statistics & numerical data*; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D017286:Polysomnography; D012307:Risk Factors; D012891:Sleep Apnea Syndromes / Q000453:epidemiology*; D012907:Smoking / Q000453:epidemiology; D014922:Wisconsin; D016387:Women's Health
keywords: Bias (epidemiology); Estrogen replacement therapy; Menopause; Obstructive; Sleep apnea; Sleep apnea syndromes; Women's health