title: Heart disease risk determines menopausal age rather than the reverse.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether a harmful cardiovascular risk profile accelerates menopause.
  
  
  BACKGROUND
  Women with an early menopause are at an increased risk of cardiovascular disease. Although increased cardiovascular risk has been proposed as consequence of menopause, the alternative hypothesis, that increased premenopausal cardiovascular risk promotes early menopause, needs to be examined.
  
  
  METHODS
  We used data from the Framingham Heart Study cohort. This study started in 1948 and has followed up participants biennially since then. Women who were premenopausal at study entry and who reached natural menopause after at least two examination rounds were included in the study (n = 695). Premenopausal age-independent levels of serum total cholesterol, relative weight, blood pressure, and Framingham risk score were determined, as well as premenopausal changes in cholesterol, body weight, and blood pressure.
  
  
  RESULTS
  A higher premenopausal serum total cholesterol level was statistically significantly associated with an earlier age at menopause, as were increases in total serum cholesterol, relative weight, and blood pressure in the premenopausal period. A decrease in total serum cholesterol during premenopause was statistically significantly associated with later age at menopause. Decreasing blood pressure was associated with a later menopausal age, but this association was not statistically significant. A decrease in relative weight was associated with a significant earlier age at menopause. Each 1% higher premenopausal Framingham risk score was associated with a decrease in menopausal age of 1.8 years (95% confidence interval -2.72 to -0.92).
  
  
  CONCLUSIONS
  The findings support the view that heart disease risk determines age at menopause. This offers a novel explanation for the inconsistent findings on cardiovascular disease rate and its relationship to menopausal age and effects of hormone replacement therapy.
authors.affiliation: Julius Center for Health Sciences and Primary Care, Utrecht University, Utrecht, The Netherlands.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Kok
authors.forename: Kristel M
authors.initials: KM
authors.lastname: van Asselt
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van der Tweel
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Peter W F
authors.initials: PW
authors.lastname: Wilson
authors.forename: Peter L
authors.initials: PL
authors.lastname: Pearson
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001794:Blood Pressure; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D008593:Menopause / Q000502:physiology*; D008594:Menopause, Premature / Q000502:physiology; D008875:Middle Aged; D017697:Premenopause; D012307:Risk Factors; D012907:Smoking
chemical_list: D002784:Cholesterol