Irregular Menstrual Cycle Length Associated with Cardiovascular Disease Risk

Huijie Zhang, MD, PhD

Credit: American Heart Association

New findings from a large, prospective study of more than 58,000 women found that irregular menstrual cycles were significantly associated with increased risks of cardiovascular disease (CVD) independent of other risk factors over a 12-year period.¹

The analysis indicated that both long (≥35 days) or short (≤21 days) menstrual cycles were associated with a higher risk of CVD and atrial fibrillation compared to normal menstrual cycle length; however, the data showed no significant associations between menstrual cycle length and regularity with stroke and heart failure.

“The association between menstrual cycle characteristics and adverse cardiovascular outcomes remains unclear,” Huijie Zhang, MD, PhD, chief physician and professor at Nanfang Hospital of Southern Medical University, said in a statement.² “Considering the increasing prevalence of heart disease – with 45% of women in Western countries affected – and related mortality, there is a need to explore these risk factors.”

A regular menstrual cycle length, lasting between 22 and 34 days, over a woman’s reproductive life, reflects normal functioning of the hypothalamic-pituitary-ovarian axis and is a vital sign of overall health in women. Irregular menstrual cycles are common endocrine disorders, with approximately 20% of women experiencing cycles of varying lengths. Literature has linked irregular cycles with insulin resistance, metabolic disturbances, hyperandrogenism, and chronic inflammation, and hormonal fluctuations of the menstrual cycle with a higher risk for arrhythmia.

However, the link between menstrual cycle characteristics with CVD and cardiovascular mortality is limited, requiring data from large, prospective studies to fill these gaps in knowledge. Using data from the UK Biobank (2006 - 2010), investigators analyzed menstrual cycle length to determine associations with overall CVD and specific CVD events in women. All female participants in the UK Biobank were asked to self-report their current menstrual cycle length and regularity, with an irregular cycle defined as a cycle length of ≤21 days or a cycle length of ≥35 days.

The main outcomes of the study included the incidence of CVD events, as well as incident CHD, myocardial infarction, heart failure, atrial fibrillation, and stroke. At the time of analysis, health outcomes data were available until November 2020. The analysis included health data from a total of 58,056 women, after exclusions for those who had reached menopause.

During a median follow-up period of 12 years, a total of 1,6223 cardiovascular events were recorded among the participants, including 827 incident CHD events, 199 myocardial infarctions, 271 strokes, 174 heart failure events, and 393 atrial fibrillations. The analysis found the cumulative incidence of CVD was higher among women with irregular menstrual cycles than those with regular menstrual cycles (adjusted hazard ratio [HR], 1.19; 95% CI, 1.07 - 1.31).

Moreover, women with menstrual cycle length ≤21 days had a 29% higher risk of CVD events (HR, 1.29 [95% CI, 1.11 - 1.50]), including CHD, heart attack, atrial fibrillation, stroke, and heart failure, compared with normal menstrual cycles. Women with longer menstrual cycles at ≥35 days experienced an 11% higher risk of CVD events (HR, 1.11 [95% CI, 0.98 - 1.56]), compared with regular-length menstrual cycles.

Regarding subtypes of cardiovascular outcomes, the analysis found women with irregular menstrual cycles were significantly associated with higher risks of atrial fibrillation (HR, 1.40; 95% CI, 1.14 - 1.72) in the multivariable-adjusted model, but not incident CHD, myocardial infarction, heart failure, and stroke. Shorter menstrual cycles were associated with a 38% higher risk of atrial fibrillation and longer menstrual cycles were associated with a 30% higher risk of atrial fibrillation, compared with regular-length menstrual cycles. The models additionally found those with short menstrual cycles had a significantly higher likelihood of CHD and myocardial infarction than those with normal cycles (adjusted HRs, 1.41 [95% CI, 1.16 - 1.72] and 1.69 [95% CI, 1.13 - 2.52]), but the results were not significant in women with long cycles.

Increased risks of CVD remained statistically significant after further adjustment for other risk factors, including age, ethnicity, body mass index, smoking status, drinking status, physical activity, baseline cholesterol levels, history of high blood pressure or type 2 diabetes, history of oral contraceptive use or hormone replacement therapy, and family history of heart disease or stroke.

Zhang and colleagues stressed the need to raise awareness that individuals with irregular menstrual cycle patterns may be more likely to develop heart disease and could experience adverse cardiovascular health consequences.

“These findings have important public health implications for the prevention of atrial fibrillation and heart attack among women and highlight the importance of monitoring menstrual cycle characteristics throughout a woman’s reproductive life,” Zhang said.²

References

1. Huang C, Lin B, Yuan Y, et al. Associations of Menstrual Cycle Regularity and Length With Cardiovascular Diseases: A Prospective Study From UK Biobank [published online ahead of print, 2023 May 24]. J Am Heart Assoc. 2023;e029020. doi:10.1161/JAHA.122.029020
2. HeartNews. Long or short menstrual cycles linked to higher risk of CVD including atrial fibrillation. EurekAlert! May 24, 2023. Accessed May 25, 2023. https://www.eurekalert.org/news-releases/989933.