Long, Irregular Menstrual Cycles Could Signal Increased Cardiovascular Risk Later in Life

Yi-Xin Wang, MD, PhD

Having irregular or long menstrual cycles could signal a greater risk of future cardiovascular disease, according to new research from the Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital.

A retrospective cohort study of women followed in the Nurses’ Health Study II, results of the study indicate those with irregular menstrual cycles or no periods at different time intervals from the ages of 14-49 years saw their risk of cardiovascular increase by 15% or greater compared to those with very regular cycles at the same ages in multivariable-adjusted analyses.

“In our prospective cohort study, irregular and long menstrual cycle lengths across the reproductive lifespan were associated with an increased risk of CVD later in life. Furthermore, we found that only a small proportion of the relation between cycle characteristics and CVD risk was driven by hypercholesterolemia, chronic hypertension, and type 2 diabetes,” wrote investigators. “Our results suggest that menstrual cycle dysfunction may be a useful marker for identifying women who are more likely to develop CVD events later in life.”

Citing limited data on the subject, the current study was launched Led by Yi-Xin Wang, MD, PhD, a postdoctoral research fellow in nutrition at Harvard T.H. Chan School of Public Health, with the intent of exploring associations of menstrual cycle characteristics across the reproductive lifespan with the risk of cardiovascular disease, with an additional interest in estimating levels of mediation by hypercholesterolemia, chronic hypertension, and type 2 diabetes. With this in mind, Wang and colleagues from Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital, designed their research endeavor as a retrospective analysis of prospective cohort data obtained from 1993-2017 within the Nurses’ Health Study II.

As part of the Nurses’ Health Study II, women enrolled in the study reported menstrual cycle regularity and length for ages 14-17 and 18-22 years at enrollment in 1989 as well as providing updated cycle characteristics in 1993, which occurred sometime between the ages of 29 and 46 years among enrolled women. The main outcomes of the investigators’ analyses were incident cardiovascular disease events of interest, which investigators defined as fatal and nonfatal coronary heart disease and stroke.

Exposures of interest for these analyses included menstrual cycle regularity and length across reproductive lifespan. For the purpose of analysis, cycle regularity was categorized as very regular (no more than 3-4 days before or after expected), regular (within 5-7 days), usually irregular, always irregular, or no periods. Additionally, cycle length was categorized as 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, or too irregular to estimate.

From the Nurses’ Health Study II, investigators obtained data related to 80,630 women for inclusion in their analyses. This cohort had a mean age at baseline of 37.7 (SD, 4.6) years, a mean baseline BMI of 25.1 (SD, 5.6) kg/m2, and a total of 1,887,517 person-years of follow-up. Among this cohort, 1816 women developed a first cardiovascular disease event during the follow-up period.

In multivariable-adjusted analyses, results indicated irregular cycles or no periods at ages 14 to 17, 18-22, or 29-46 years had hazard ratios for CVD of 1.15 (95% CI, 0.99-1.34), 1.36 (95% CI, 1.06-1.75), and 1.40 (95% CI, 1.14-1.71), respectively, compared to women reporting very regular cycles at the same ages. Further analysis demonstrated those with a cycle length of 40 days or more or a cycle to irregular to irregular to estimate from ages 18-22 or 29-46 years had hazard ratios for CVD of 1.44 (95% CI, 1.13-1.84) and 1.30 (95% CI, 1.09-1.57), respectively, compared to women reporting a cycle of 26-31 days. In mediation analyses, investigators found development of hypercholesterolemia, chronic hypertension, and type 2 diabetes explained 5.4-13.5% of the observed associations.

“Over 24 years of follow-up, an increased rate of CVD was observed among women with greater menstrual cycle irregularity and longer menstrual cycle length in both early adulthood and mid-adulthood; similar trends were also observed for cycle characteristics in adolescence, but these were weaker than those during adulthood,” investigators added.

This study, “Menstrual Cycle Regularity and Length Across the Reproductive Lifespan and Risk of Cardiovascular Disease,” was published in JAMA Network Open.