Long, irregular menstrual cycles may predict premature mortality
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Women reporting consistently long or irregular menstrual cycles are more likely to die of cancer or cardiovascular disease compared with women who report regular menses, according to data published in The BMJ.
“Our findings suggest that menstrual cycle characteristics throughout a woman’s life course are important markers of her overall health status,” Jorge E. Chavarro, MD, ScD, associate professor of nutrition, epidemiology and medicine at the Harvard T.H. Chan School of Public Health and Harvard Medical School, told Healio. “Moreover, our findings suggest that the relation of long or irregular cycles with premature mortality is not restricted to women with overweight or obesity, polycystic ovary syndrome or other conditions known to affect menstrual bleeding patterns.”
Irregular menstrual cycles have been linked to increased risk for type 2 diabetes, and some studies suggest an increased risk for CVD, but an association with premature mortality has not been assessed in a large study with long-term follow-up, according to study researcher JoAnn E. Manson, MD, DrPH, FACE, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of medicine and the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School.
“It was surprising there was a substantial association between irregular and long menstrual cycles and increased risk for premature death that persisted after adjusting for BMI, physical activity [and] lifestyle factors and after excluding women who had hirsutism and clear signs of PCOS,” Manson told Healio. “It seemed to go beyond that; however, we do know that regular cycles are a marker of good health. To have regular menstrual cycles through reproductive years means you have good functioning of the hypothalamic-pituitary-gonadal axis. Clinicians should always ask about menstrual cycle regularity during reproductive years and consider incorporating this information as a vital sign.”
Nurses’ Health Study data
Chavarro and colleagues analyzed data from 79,505 premenopausal women participating in the Nurses’ Health Study II without CVD, cancer or diabetes at baseline, who reported the usual length and regularity of their menstrual cycles at age 14 to 17 years and 18 to 22 years (recalled in baseline questionnaires in 1989), and again at age 29 to 46 years in questionnaires completed in 1993 (mean baseline age, 38 years). Cycle regularity was reported as very regular (within 3-4 days), regular (within 5-7 days), usually irregular, and always irregular or no periods. Cycle length was reported as 21 days or less, 21 to 25 days, 26 to 31 days, 32 to 39 days, 40 to 50 days, or more than 50 days or too irregular to estimate.
Primary outcomes were all-cause and cause-specific premature mortality during 24 years of follow-up, defined as death before age 70 years, estimated using Cox proportional hazards models.
Researchers observed 1,975 premature deaths before age 70 years during follow-up, including 894 from cancer and 172 from CVD.
Irregular cycles, higher risk
Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up vs. women who reported very regular cycles in the same age ranges. The crude cumulative incidence of premature death was higher among women reporting irregular or long menstrual cycles vs. those with regular or short cycles. The mortality rate per 1,000 person-years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23, respectively, for cycle characteristics at age 14 to 17 years; 1 and 1.37, respectively, for cycle characteristics at age 18 to 22 years; and 1 and 1.68, respectively, for cycle characteristics at age 29 to 46 years.
Compared with women reporting a very regular menstrual cycle, women were more likely to die before age 70 years when reporting always have an irregular or no period at age 14 to 17 years (HR = 1.18; 95% CI, 1.02-1.37), age 18 to 22 years (HR = 1.37; 95% CI, 1.09-1.73) and age 29 to 46 years (HR = 1.39; 95% CI, 1.14-1.7).
Similarly, in fully adjusted models, women who reported a usual cycle length of 40 days or more or too irregular to estimate from age 18 to 22 years and 29 to 46 years had HRs for premature death during follow-up of 1.34 (95% CI, 1.06-1.69) and 1.4 (95% CI, 1.17-1.68), respectively, compared with women reporting a cycle length of 26 to 31 days in the same age range.
“When the effect of changes in menstrual cycle patterns across the reproductive life span was tested, the risk of premature mortality was strongest among women who consistently reported long or irregular cycles,” the researchers wrote.
Researchers noted that the higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers.
Menses as vital sign
“What our findings indicate is that primary care providers — and not only providers of reproductive health services — should be aware of women’s menstrual cycle characteristics and include them as a vital sign when evaluating women’s overall health status,” Chavarro said. “While there is a substantial body of literature linking menstrual cycle characteristics and conditions associated with long or irregular cycles to a number of major chronic diseases, data linking menstrual cycle characteristics to premature mortality is still scarce. Additional research addressing this particular issue would be helpful.”
Manson said the findings show disruption of normal menstrual cycling may reflect hormonal and metabolic perturbations.
“We are not suggesting that the less frequent, irregular or longer menstrual cycles are cause for early death,” Manson said. “This is a marker for some of these perturbations in hormones and metabolism.”
For more information:
JoAnn Manson, MD, DrPH, FACE, can be reached at Harvard Medical School, 900 Commonwealth Ave., Third Floor, Boston, MA 02215; email: jmanson@rics.bwh.harvard.edu.
Perspective
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Mary Jane Minkin, MD, FACOG
This study by Wang and colleagues reports data collected during the Nurses’ Health Study II examining the effects of menstrual cycle regularity and length on premature mortality. Like the first Nurses’ Health Study, it is a prospective cohort study of very reliable participants. The findings of the first Nurses’ Health Study was the largest and earliest study that showed the effects of estrogen therapy on the development of cardiovascular disease among postmenopausal women.
The current study is an elaborate analysis, reviewing potential confounding variables, and shows that women with significant menstrual irregularity and long menstrual cycles are at a significantly higher risk for premature death, particularly from CV causes, before age 70 years. The additional risk factor of smoking further increases that risk. The plausible explanation is that these women, even if not diagnosed with classical polycystic ovary syndrome, may well be hyperandrogenic and hyperinsulinemic, raising their CV risks.
The authors correctly suggest that the menstrual cycle should be considered an important vital sign throughout women’s lives. Primary care providers have started to consider pregnancy complications, such as preeclampsia and diabetes, as germane to women’s subsequent health. Impressing on young women that these histories suggest risk factors for premature death could improve compliance with smoking cessation, increasing physical activity, nutritional improvements and weight reduction, and continuing medical follow-up for other CV risk factors.
One could also hope that a focus such as this study’s could also encourage primary care providers to attend to the significant risk factor of premature menopause as a major risk for the development of CVD.
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