Irregular menstrual cycles linked to premature mortality risk

Published 06 October 2020

Irregular and long menstrual cycles in adolescence and adulthood have been associated with a greater risk of premature mortality than regular cycles in a large cohort study. The associations were found strongest for deaths from cardiovascular disease.

The Nurses’ Health Study, which has been turning out prospective observational data since 1976 on risk factors for chronic diseases in women, has now in its second incarnation, added a little more to the growing body of evidence linking menstrual cycle irregularity with long-term health and mortality. Dysfunctional periods, as evident in PCOS, for example, have long been linked to an increased likelihood of coronary heart disease and other chronic conditions.

Now, the latest Nurses’ Health Study of nearly 80,000 women has established an association between irregular and long menstrual cycles in adolescence and adulthood and an increased chance of dying early.(1) A higher mortality risk before age 70 is stronger for cardiovascular disease than for cancer and other causes, and slightly stronger among current smokers.

The results are observational so cannot establish cause, say the authors, who nevertheless cite the large number of participants with a high follow-up rate - over almost a quarter of a century – as the strengths of the study. The authors add that their results demonstrate the need for including menstrual cycle characteristics throughout the reproductive lifespan in any assessment of women’s general health status.

Data on 79,505 premenopausal women (average age 38 years) taking part in the Nurses’ Health Study II were included, none of them with a history of cardiovascular disease, cancer, or diabetes. Throughout the follow-up participants reported usual length and regularity of menstrual cycles at three age points (14-17, 18-22 and 29-46). Reported cycle regularity ranged from very regular (within 3-4 days) to always irregular and no periods. Cycle length ranged from 21 days or less to more than 50 days (or too irregular to estimate), with 26-31 days reported by the majority (75%) of women with a regular cycle.

Information on lifestyle, body weight, smoking status and other factors such as self-reported height and race were gathered at baseline.

Results showed that 1975 premature deaths occurred during follow-up, including 894 from cancer and 172 from cardiovascular disease. Mortality rates were higher among women who always experienced irregular menstrual cycles than those reporting very regular cycles (ages 14-17 hazard ratio 1.18; ages 18-22 HR 1.37; and ages 29-46, HR 1.39).

Similarly, women who reported a usual cycle length of 40 days or more at ages 18-22 and 29-46 were more likely to die prematurely than participants who reported a usual cycle length of 26-31 days in the same age ranges.

Overall, this association between early death and cycle length/regularity was strongest in association with cardiovascular disease.

Compared with women who reported very regular menstrual cycles, those with irregular cycles or no periods were more likely to suffer from conditions which included hypertension (13.2% vs 6.2%) and a family history of diabetes (19.4% vs 15.8%). Similar results were observed among women with a usual long cycle length (40 days or more) or cycles too irregular to estimate when compared with women with a normal cycle length.

Despite a prevalence of higher BMI among women with disrupted cycles (28 vs 25), the authors found no evidence that modifying this or other lifestyle and psychological factors affected mortality outcomes. Instead, they suggest that a disrupted hormonal environment, smoking and possibly oral contraceptive use are more likely mechanisms underlying the association.

1 Wang Yi-Xin, Arvizu M, Rich-Edwards J, et al. Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study; BMJ 2020; doi:10.1136/bmj.m3464


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