Irregular periods: an emerging cardiovascular risk factor in women

Dr Charlotte Nélis, medical gynecologist in Aix-en-Provence and ambassador for the Agir pour le Cœur des femmes endowment fund, comments on an article recently published in the American journal JAMA* on this new marker of cardiovascular risk in women: irregular periods.

The menstrual cycle runs from the first day of menstruation to the first day of the following period. It is defined as long if it lasts more than 35 days. It is considered regular if menstruation occurs every month, give or take a few days. Long menstrual cycles are known to be associated with more cardiovascular risk factors, such as hypercholesterolemia, hypertension and type II diabetes. But few data have studied the impact of cycle length and regularity on the occurrence of arterial events.
An American study published in 2022 in the journal JAMA suggests this hypothesis. This cohort study included over 80,000 nurses between 1993 and 2017. They all completed a questionnaire describing their cycles, excluding periods of pregnancy and use of oral contraception. The average age of the women in the study was 37. 9.1% of them reported irregular cycles; 13.9% long cycles of over 32 days. It should be noted that patients with irregular cycles had a higher BMI (body mass index) than women with regular cycles, more hypercholesterolemia and more hypertension. Over 24 years of prospective follow-up, 1816 (2.3%) women developed a first arterial cardiovascular event: coronary pathology, myocardial infarction or stroke.

Statistical analysis of the study showed that :
- Women with irregular cycles or a period without menstruation had a greater risk of developing a cardiovascular event after the age of 50 than women with regular cycles.
- Women with long cycles of 40 days or more had a greater risk of developing a cardiovascular event after age 50 than women with a normal cycle length of 26 to 31 days.
- Women with regular cycles during adolescence, which become irregular after age 29, have an increased risk of cardiovascular events.
The most common cardiovascular risk factors in these associations were hypercholesterolemia, chronic hypertension and type II diabetes.

The strengths of this study are the long follow-up time in a large cohort of women, and the analysis including cardiovascular risk factors.
On the other hand, this study did not take into account any gynecological diagnoses that might be at the origin of menstrual cycle disorders, such as polycystic ovary syndrome (PCOS) or premature ovarian failure, although these two pathologies are now known to be at greater cardiovascular risk. Furthermore, 23% of patients had not completed the questionnaire at all the ages requested, and were therefore excluded. Finally, no information on non-oral hormonal contraception was provided.

TAKE HOME MESSAGE: Irregular or long cycles should be investigated not only for gynaecological pathology, but also for associated cardiovascular risk factors. It remains to be seen whether treatment of these menstrual disorders reduces the increased risk of cardiovascular events evoked in this study.

*Menstrual Cycle Regularity and Length Across the Reproductive Lifespan and Risk of Cardiovascular Disease, Yi-Xin Wang et al, JAMA 2022

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