title: Ovarian hormones and vascular disease.
abstract: OBJECTIVE
  Observational studies have shown benefit of hormone therapy, particularly estrogen, in women who begin treatment in the perimenopausal/early postmenopausal period, whereas randomized controlled trials of such therapy in older postmenopausal women have reported harm. These apparently paradoxical findings have led to the 'timing hypothesis' which proposes that estrogen signaling is altered in older women, converting vasoprotective to vasotoxic effects. We reviewed recent literature on age-dependent effects of hormones (particularly estrogen) on the vasculature of women and the fundamental cellular/molecular mechanisms responsible for those effects.
  
  
  RESULTS
  Observational studies have shown that early menopause is associated with adverse cardiovascular disease outcomes and that starting hormone therapy in the perimenopausal period reduces these outcomes. Mechanistic studies have shown that estrogen modulates injury-induced inflammation, growth factor expression, and oxidative stress in arteries and vascular smooth muscle cells isolated from young women but that these vasoprotective mechanisms are lost in women who are aged and/or deprived of estrogen for prolonged periods of time.
  
  
  CONCLUSIONS
  The vasoprotective effects of estrogen are age-dependent and disappear with aging and/or estrogen deprivation. Future studies designed to preserve the vasoprotective effects of estrogen in older women are needed and may lead to innovative approaches to improving women's cardiovascular health.
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA. fadihage@uab.edu
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Hage
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
mesh_terms: D000367:Age Factors; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D014652:Vascular Diseases / Q000517:prevention & control*
chemical_list: D004967:Estrogens; D004958:Estradiol