Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

Yi-Xin Wang; Mariel Arvizu; Janet W Rich-Edwards; Jennifer J Stuart; JoAnn E Manson; Stacey A Missmer; An Pan; Jorge E Chavarro

doi:10.1136/bmj.m3464

Longevity and Reproductive Aging Lifespan Health

Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

Wang YX, Arvizu M, Rich-Edwards JW, Stuart JJ, Manson JE, Missmer SA, Pan A, Chavarro JE

Published September 30, 2020 BMJ, m3464

DOI 10.1136/bmj.m3464 PMC PMC7526082

RRM Academy Synopsis

Irregular or long menstrual cycles linked to earlier deaths in nurses

In a prospective cohort of 79 505 nurses followed for 24 years, irregular or long menstrual cycles were linked to higher mortality before age 70. The link held for cycles reported in adolescence and in adulthood. It was stronger for cardiovascular deaths in adulthood.

Key Findings

Of 1975 deaths before age 70 over 1 879 769 person years, 894 were due to cancer and 172 to cardiovascular disease.
Premature mortality hazard ratios were 1.18 (1.02 to 1.37), 1.37 (1.09 to 1.73) and 1.39 (1.14 to 1.70) for the most irregular versus very regular cycles at ages 14-17, 18-22 and 29-46.
Cycles of 40 days or more, or too irregular to estimate, carried hazard ratios of 1.34 (1.06 to 1.69) and 1.40 (1.17 to 1.68) at ages 18-22 and 29-46, against 26-31 days.
Irregularity maintained from ages 14-17 to 29-46 carried a hazard ratio of 1.57 (1.32 to 1.88) against regularity maintained across the same span.
At ages 29-46, irregular cycles or no periods carried hazard ratios of 1.33 (1.09 to 1.63) for cancer death and 1.59 (1.04 to 2.45) for cardiovascular death.

Interpretation

This prospective cohort study followed participants in the Nurses’ Health Study II, who were free of diabetes, cancer and cardiovascular disease at the start. Results were adjusted for age, smoking, body mass index, diet and other factors, and they held when women with endometriosis or uterine fibroids were excluded. The authors note that most participants were white women with a shared profession and education level. The findings support larger studies of menstrual cycle pattern as an early marker of long-term health.

RRM Context

Restorative reproductive medicine treats the menstrual cycle as a vital sign. Pediatric and obstetric-gynecologic professional societies hold the same view for adolescents, as the authors note. The paper describes regular cycles as a sign of a well-working hormonal axis linking brain and ovaries. Restorative care records cycle length and regularity and looks for the cause of an irregular cycle before treating it.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years).

Design

Prospective cohort study.

Setting

Nurses' Health Study II (1993-2017).

Participants

79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years.

Main Outcome Measures

Hazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models.

Results

During 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers.

Conclusions

Irregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.

Topics

Longevity and Reproductive Aging › Lifespan Health › Cycle as a Lifespan Health Marker · Menstrual Cycle › Cycle Across the Lifespan › Cycle and General Health

Yi-Xin Wang, Mariel Arvizu, Janet W Rich-Edwards, Jennifer J Stuart, JoAnn E Manson, Stacey A Missmer, An Pan, Jorge E Chavarro

Y Wang, M Arvizu, J Rich-Edwards, Jen Stuart, Jenny Stuart, J Stuart, J Manson, S Missmer, A Pan, J Chavarro

DOI 10.1136/bmj.m3464 10.1136/bmj.m3464 Wang et al. 2020, Wang 2020

Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

Irregular or long menstrual cycles linked to earlier deaths in nurses

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Related research