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

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.

SUBMITTER: Wang YX

PROVIDER: S-EPMC7526082 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Wang Yi-Xin YX Arvizu Mariel M Rich-Edwards Janet W JW Stuart Jennifer J JJ Manson JoAnn E JE Missmer Stacey A SA Pan An A Chavarro Jorge E JE

BMJ (Clinical research ed.) 20200930

<h4>Objective</h4>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).<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>Nurses' Health Study II (1993-2017).<h4>Participants</h4>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, a ...[more]

PMID: 32998909

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Project description:BackgroundLocal inflammation plays an important role in normal folliculogenesis and ovulation, and conditions of chronic systemic inflammation, such as obesity and polycystic ovarian syndrome, can disrupt normal follicular dynamics.ObjectiveThis study aimed to determine the association between systemic inflammation, as measured by C-reactive protein levels, and menstrual cycle length.Study designThis study was a secondary analysis using data from Time to Conceive, a prospective time-to-pregnancy cohort study. The association between cycle length and C-reactive protein was analyzed using multivariable linear mixed and marginal models adjusted for age, race, education, body mass index, time since oral contraceptive use, alcohol, smoking, caffeine consumption, and exercise. Time to Conceive enrolled women aged 30 to 44 years with no history of infertility who were attempting to conceive for <3 months. Serum C-reactive protein levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months.ResultsMain outcome measures included menstrual cycle length and follicular and luteal phase lengths. Multivariable analysis included 1409 cycles from 414 women. There was no linear association between C-reactive protein levels and menstrual cycle length. However, compared with <1 mg/L, a C-reactive protein level >10 mg/L was associated with >3 times the odds (adjusted odds ratio, 3.7; 95% confidence interval, 1.67-8.11) of long cycles (defined as ≥35 days). When evaluating follicular phase length, a C-reactive protein level of >10 mg/L was associated both with follicular phases that were 1.7 (95% confidence interval, 0.23-3.09) days longer and with >2 times the odds of a long follicular phase (adjusted odds ratio, 2.2; 95% confidence interval, 1.05-4.74).ConclusionThere is a potential pathophysiological association between systemic inflammation and menstrual cycle changes. Further studies are needed to determine if systemic inflammation alters the menstrual cycle or if long menstrual cycles are a marker for elevated systemic inflammation.

Project description:BackgroundMenstrual cycle characteristics are linked to reproductive function and long-term health outcomes. This study aimed to evaluate menstrual cycle patterns, characterized by regularity and length, and associated factors among women in the Korea Nurses' Health Study.MethodsA total of 9335 premenopausal women aged 22-45 years were included in this cross-sectional study. Regularity and length of menstrual cycles were self-reported, and their associations with reproductive, lifestyle, and occupational factors were examined using binomial and multinomial logistic regression models. Adjusted least-square means of menstrual distress, depressive symptoms, stress, fatigue, anxiety, and sleep problems were estimated according to menstrual cycle characteristics using generalized linear models.ResultsTwenty-one percent of nurses reported having irregular menstrual cycles (variability > 7 days). Ten percent, 64%, and 26% had menstrual cycle length of < 26, 26-31, and 32-50 days, respectively. Variability and length of cycles decreased with age and increased with age at menarche. Parous women showed low tendency of irregular cycles. Women with body mass index (BMI) > 25 kg/m2 had higher odds of irregular (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.40-2.03) and long cycles (OR 1.31; 95% CI 1.08-1.58) than those with BMI 18.5- < 23 kg/m2. Irregular cycles were less common in women performing vigorous physical activity, but more common in those with prolonged standing or frequent heavy lifting at work. Frequent rotating night shift was associated with irregular cycles among nulliparous women. Levels of menstrual and premenstrual distress, depressive symptoms, perceived stress, physical and mental fatigue, anxiety, and sleep problems were higher in women with irregular cycles than in those with regular cycles (p < 0.001, each).ConclusionsThe study suggests that irregular and long menstrual cycles are associated with reproductive, lifestyle, and occupational factors; also with menstrual distress and perceived health status. Our findings contribute to a better understanding of potential risk factors for menstrual dysfunction, and thus, may help improve women's health.

Project description:BACKGROUND:There is increasing information characterizing menstrual cycle length in women, but less information is available on the potential differences across lifestyle variables. OBJECTIVE:This study aimed to describe differences in menstrual cycle length, variability, and menstrual phase across women of different ages and BMI among a global cohort of Flo app users. We have also reported on demographic and lifestyle characteristics across median cycle lengths. METHODS:The analysis was run based on the aggregated anonymized dataset from a menstrual cycle tracker and ovulation calendar that covers all phases of the reproductive cycle. Self-reported information is documented, including demographics, menstrual flow and cycle length, ovulation information, and reproductive health and diseases. Data from women aged ?18 years and who had logged at least three cycles (ie, 2 completed cycles and 1 current cycle) in the Flo app were included (1,579,819 women). RESULTS:Of the 1.5 million users, approximately half (638,683/1,579,819, 40.42%) were aged between 18 and 24 years. Just over half of those reporting BMIs were in the normal range (18.5-24.9 kg/m2; 202,420/356,598, 56.76%) and one-third were overweight or obese (>25 kg/m2; 120,983/356,598, 33.93%). A total of 16.32% (257,889/1,579,819) of women had a 28-day median cycle length. There was a higher percentage of women aged ?40 years who had a 27-day median cycle length than those aged between 18 and 24 years (22,294/120,612, 18.48% vs 60,870/637,601, 9.55%), but a lower percentage with a 29-day median cycle length (10,572/120,612, 8.77% vs 79,626/637,601, 12.49%). There were a higher number of cycles with short luteal phases in younger women, whereas women aged ?40 years had a higher number of cycles with longer luteal phases. Median menstrual cycle length and the length of the follicular and luteal phases were not remarkably different with increasing BMI, except for the heaviest women at a BMI of ?50 kg/m2. CONCLUSIONS:On a global scale, we have provided extensive evidence on the characteristics of women and their menstrual cycle length and patterns across different age and BMI groups. This information is necessary to support updates of current clinical guidelines around menstrual cycle length and patterns for clinical use in fertility programs.

Dataset Information

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

Publications

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

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