Irregular menstrual cycles linked to risk of cancer in later life


Irregular and long menstrual cycles in early life have been associated with a statistically significant greater risk of developing certain cancers than regular cycles in a large cohort study. The associations were found strongest for obesity-related cancers.

Obesity-related cancers must now be included in the list of long-term health consequences of dysfunctional periods, say the authors of the latest report from the long-running Nurses’ Health Study II.(1) Based on data from nearly 79,000 women, the results show that those who experience irregular or long cycles in early life have a statistically significantly higher risk of developing cancer in mid-adulthood – especially (obesity-related) endometrial and colorectal cancers. Cycle irregularity, as evident in PCOS for example, has long been linked to an increased likelihood of coronary heart disease and other chronic conditions.

This latest study provides yet more evidence that long-term health and mortality is indeed linked to menstrual cycle irregularity, a condition experienced by up to one in five women of reproductive age. Just over a year ago, Focus on Reproduction reported on findings from the same ongoing Nurses’ Health Study II showing an association between irregular and long menstrual cycles and increased odds of early death.(2) The authors of this new investigation say the association with increased cancer risk may now warrant targeted screening of women aged 29-46 years who experience long or irregular menstrual cycles.

An association has been identified in previous research between breast and endometrial cancer risks and long and irregular menstrual cycles (or with a diagnosis of PCOS), with lower odds of being diagnosed with the former but a higher risk for the latter. However, epidemiological studies have primarily focused on the relationships of cycle characteristics or PCOS with risk of gynaecological (and not other) cancers, and a comprehensive evaluation of the association between menstrual length and irregularity with cancer development is still lacking.

In an attempt to address this, the authors of this 20-plus year follow-up study (1989 to 2015) assessed the link, throughout the reproductive lifespan, between long and irregular menstrual cycles and cancers (total invasive cancer, obesity-related and non-obesity related).

Data were included from the Nurses’ Health Study II on 78,943 premenopausal women in the US none of whom had a history of cancer. Participants reported usual length and regularity of menstrual cycles at three age points (14-17, 18-22 and 29-46). Their reported menstrual cycle regularity ranged from very regular (within 3 days) to always irregular or no period; cycle length ranged from 21 days or less to more than 50 days (or too irregular to estimate).

Results during follow-up showed 5794 cancer cases as reported through questionnaires and confirmed via medical records. The commonest cancers diagnosed (66% of all cases) were pre/post-menopausal breast, endometrial, melanoma and thyroid.

Women who reported irregular menstrual cycles at age 29-46 years had a 11% higher risk of total cancer and 23% higher odds of obesity-related cancer than those in the same age group who reported very regular cycles.

Of obesity-related cancers specifically (n = 2743), the association among women at age 29-46 years with irregular/long cycles was strongest for endometrial cancer (HR 1.39); and at age 14-17 years the association was strongest for colorectal (HR=1.36). Women who reported irregular cycles at both these time points had a 24% increased cancer risk during follow-up which was driven by obesity-related cancers, particularly endometrial. Similarly, a switch from regular to irregular cycles was associated with a higher risk for obesity-related cancers, particularly postmenopausal breast cancer but a lower risk was observed for non-obesity-related cancers.

The results are observational only so cannot establish causation, but the authors suggest they may stem from the hormonal crosstalk of sex steroids, insulin, and insulin-like growth factors. Despite the high prevalence of overweight/obesity in women reporting long/irregular cycles, BMI did not modify the effect. Indeed, the relationship between long menstrual cycles/irregularity and cancer persisted after adjustment for BMI and a range of other factors including lifestyle, and was not statistically significant for different BMI levels, smoking status or clinical signs of excess androgens.

Instead, the authors say the associations between cancer and menstrual cycles may reflect a shared hormonal environment between obesity and irregular cycles.

1. Wang S, Wang Y, Sandoval-Insausti H, et al. Menstrual cycle characteristics and incident cancer: a prospective cohort study. Human Reprod 2021; doi.org/10.1093/humrep/deab251
2. See https://www.focusonreproduction.eu/article/News-in-Reproduction-cycles



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