Age at Menarche and Risk of Cardiovascular Disease Outcomes: Findings From the National Heart Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation

J Am Heart Assoc. 2019 Jun 18;8(12):e012406. doi: 10.1161/JAHA.119.012406. Epub 2019 Jun 5.


Background Previous studies have reported an association between the timing of menarche and cardiovascular disease ( CVD ). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events ( MACE ). Methods and Results A total of 648 women without surgical menopause undergoing coronary angiography for suspected ischemia in the WISE (Women's Ischemia Syndrome Evaluation) study were evaluated at baseline and followed for 6 years (median) to assess major adverse CVD outcomes. MACE was defined as the first occurrence of all-cause death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization. Age at menarche was self-reported and categorized (≤10, 11, 12, 13, 14, ≥15 years) with age 12 as reference. Total estrogen time and supra-total estrogen time were calculated. Cox regression analysis was performed adjusting for CVD risk factors. Baseline age was 57.9 ± 12 years (mean ± SD ), body mass index was 29.5 ± 6.5 kg/m2, total estrogen time was 32.2 ± 8.9 years, and supra-total estrogen time was 41.4 ± 8.8 years. MACE occurred in 172 (27%), and its adjusted regression model was J-shaped. Compared with women with menarche at age 12 years, the adjusted MACE hazard ratio for menarche at ≤10 years was 4.53 (95% CI 2.13-9.63); and at ≥15 years risk for MACE was 2.58 (95% CI , 1.28-5.21). Conclusions History of early or late menarche was associated with a higher risk for adverse CVD outcomes. These findings highlight age at menarche as a potential screening tool for women at risk of adverse CVD events. Clinical Trial Registration URL : . Unique identifier: NCT00000554.

Keywords: cardiovascular disease outcomes; estrogen; menarche; risk factors; women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Aged
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology*
  • Child
  • Coronary Angiography
  • Female
  • Heart Diseases / complications
  • Heart Diseases / epidemiology*
  • Humans
  • Menarche*
  • Middle Aged
  • Myocardial Ischemia / complications
  • Myocardial Ischemia / diagnostic imaging
  • Prospective Studies
  • Risk Assessment

Associated data