Take heed of menstrual cycle characteristics in women from start to finish of reproductive years

Irregular and longer menstrual cycles during adolescence and adulthood may be associated with a greater risk of premature death before the age of 70 years, with stronger associations between early mortality and cardiovascular disease (CVD), and smoking, according to a recent analysis of data from the long-running Nurses’ Health Study II, which ran from 1993-2017. Results are published in The BMJ.

“Regular menstrual cycles reflect normal functioning of the hypothalamic-pituitary-ovarian axis, a vital sign of women’s general health. Irregular and long menstrual cycles, often attributed to the functional disruption of the hypothalamic-pituitary-ovarian axis, are, however, common among women of reproductive age. They have been associated with greater risk of non-communicable diseases, including ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems, through mechanisms probably related to a disrupted hormonal environment (e.g., hyperinsulinemia), chronic inflammation, and metabolic disturbances (e.g., insulin resistance, dyslipidemia, and metabolic syndrome),” wrote lead author Yi-Xin Wang, PhD, Harvard T.H. Chan School of Public Health, Boston, MA, and colleagues. “Evidence linking irregular or long menstrual cycles with mortality is, however, limited.”

In their prospective cohort study, Wang and colleagues used data from the Nurses’ Health Study II—conducted from 1993-2107—from 79,505 premenopausal women (mean age: 37.7 years) with no history of CVD, cancer, or diabetes who were followed for 24 years. Participants reported the usual length and regularity of their menstrual cycles during three life periods: ages 14-17 years, 18-22 years, and 29-46 years.

Women who reported irregular cycles or no periods were more likely to have a higher BMI compared to those with very regular cycles (28.2 versus 25.0, respectively), hypertension (13.2% versus 6.2%), hypercholesterolemia (23.9% versus 14.9%), hirsutism (8.4% versus 1.8%), endometriosis (5.9% versus 4.5%), uterine fibroids (10.0% versus 7.8%), and a family history of diabetes (19.4% versus 15.8%).

During follow-up, there were 1,975 deaths before age 70 years, including 894 from cancer and 172 from CVD.

Wang and colleagues found that women who had irregular menstrual cycles had higher mortality rates during follow-up and for all three age spans compared with those who reported very regular cycles.

  • During the ages of 14-17 years, the crude mortality rate per 1,000 person-years of follow-up in women with very regular cycles was 1.05, compared with 1.23 in those who reported consistently irregular cycles (adjusted HR for premature death: 1.18; 95% CI: 1.02-1.37).
  • From ages 18-22 years, crude mortality rates per 1,000 person-years were 1.00 and 1.37, respectively (adjusted HR for premature death: 1.37; 95% CI: 1.09-1.73).
  • Finally, between ages 29-46 years, crude mortality rates per 1,000 person-years were 1.00 and 1.6 (adjusted HR for premature death: 1.39; 95% CI: 1.14-1.70).

Women with longer menstrual cycles also fared worse than those with shorter cycles. Those with a usual menstrual cycle length of 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than those who had a usual cycle length of 26-31 days during the same age ranges (HR: 1.34; 95% CI: 1.06-1.69; and HR: 1.40; 95% CI: 1.17-1.68, respectively).

Wang and fellow researchers also found that these associations were strongest for deaths related to CVD, with premature deaths associated with CVD slightly higher than those associated with cancer or death from other causes. Associations between higher mortality and long, irregular menstrual cycles were stronger among women who were current smokers.

These most recent results from Wang and colleagues support those from previous studies.

“Irregular ovarian function is not healthy for women and is associated with early death. This is consistent with other studies linking shorter reproductive lifespan and premature/early menopause to adverse health outcomes and earlier mortality,” said Stephanie S. Faubion, MD, MBA, FACP, NCMP, IF, who is Director of the Mayo Clinic Center for Women’s Health, Jacksonville, FL, and Medical Director of The North American Menopause Society.

Faubion also noted that the study has some limitations.

“Some limitations that the authors mention [are] that cycle regularity relied on the participant’s interpretation of ’irregular’ and might result in some misclassification and about one-fourth of participants didn’t fully report their menstrual cycle characteristics across the entire reproductive lifespan, potentially introducing selection bias. There could be residual confounding (other unreported or unknown factors could have influenced these results),” she told BreakingMED.

Another limitation is the study’s observational nature. Nevertheless, its strengths include a large cohort, the high follow-up rate over many years, and the inclusion of data on menstrual cycles from three different time points in participants’ reproductive lifespan.

According to Faubion, the take-home message is clear:

“Clinicians need to include menstrual cycle characteristics throughout the reproductive years as part of their general health assessment. Lifestyle measures may be helpful to help mitigate risk (e.g., weight loss, exercise),” she concluded.

  1. An analysis of data from the Nurses’ Health Study showed that irregular and long menstrual cycles during adolescence and adulthood are associated with a greater risk of early death.

  2. In women with longer and more irregular menstrual cycles throughout their lives, researchers found stronger associations between early mortality and cardiovascular disease and current smoking status.

E.C. Meszaros, Contributing Writer, BreakingMED™

This study was supported by the National Institutes of Health (NIH).

Wang received support from the NIH.

Cat ID: 191

Topic ID: 83,191,191,138,192,925