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

Abstract

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/m 2 , 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 : http://www.clinicaltrials.gov . Unique identifier: NCT 00000554.

Early age at menarche and metabolic cardiovascular risk factors: mediation by body composition in adulthood

“…On the other hand, we did not observe an association between age at menarche and other metabolic cardiovascular risk factors, such as HDL-cholesterol and C-reactive protein, unlike other studies 6 , 16 , 17 , 46 . This may have occurred because we evaluated women at younger age (30 years) than the previous studies.…”

A Systematic Literature Review of Factors Affecting the Timing of Menarche: The Potential for Climate Change to Impact Women’s Health

“…Cardiovascular disease [94], including increased carotid artery intima-media thickness (an indicator of cardiac age and a risk factor for cardiovascular disease) [95] was associated with early menarche. Another study found that either early or late menarche was associated with higher risk of adverse cardiovascular disease outcomes [96], perhaps indicating that being either early or late with regards to menarche puts a strain on cardiovascular development.…”

Modern dietary pattern is prospectively associated with earlier age at menarche: data from the CHNS 1997–2015

“…Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, PR China. 4 Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, PR China. 5 Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.…”

“…Early age at menarche is a risk factor for insulin resistance [ 1 ], type 2 diabetes [ 2 , 3 ], cardiovascular diseases [ 4 ] and hormone-related cancers [ 5 – 7 ]. Data from previous studies have consistently pointed to the fact that there appears to be a trend towards earlier attainment of menarche among Chinese girls [ 8 , 9 ].…”