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Physical activity is not related to risk of early menopause in a large prospective study

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Physical activity is not related to risk of early menopause in a large prospective study

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Study question: Is physical activity associated with incident early menopause? Summary answer: Physical activity is not associated with incident early menopause. What is known already: Lifestyle factors such as physical activity may influence menopause timing, but results from prior research are inconsistent. Study design, size, duration: We evaluated the association between physical activity and the occurrence of early natural menopause in a prospective cohort study, the Nurses' Health Study II. Women were followed prospectively from 1989 to 2011. Participants/materials, setting, methods: Our analysis included 107 275 women who were premenopausal at baseline. Menopause status was self-reported biennially. Time per week participating in specific activities was reported approximately every 4 years and used to calculate metabolic task hours per week (MET h/week). We used Cox proportional hazards model to evaluate the association between physical activity and incidence of natural menopause before age 45 years while controlling for potential confounding factors. Main results and the role of chance: There were 2 786 study members who experienced menopause before the age of 45. After adjustment for age, smoking and other factors, we observed no association between adulthood physical activity and early menopause. For example, compared to women reporting <3 MET h/week, the hazard ratio for women in the highest category (≥42 MET h/week) of cumulatively-averaged total physical activity was 0.89 (95% confidence interval: 0.76-1.04; P-trend: 0.26). Neither moderate nor strenuous activity in adolescence and young adulthood were related to risk. The relation of physical activity and early menopause did not vary across strata of body mass index or smoking status. Limitations, reasons for caution: Physical activity and menopausal status were self-reported, but repeated assessment of physical activity and prospective report of menopause status likely reduce the potential for non-differential misclassification. While the majority of our study participants were white, it is unlikely that the physiological relation of activity and early menopause varies by ethnicity. Wider implications of the findings: Findings from our large prospective study do not support an important association between physical activity and early menopause. Study funding/competing interest(s): This project was supported by UM1CA176726 and R01HD078517 from the National Institutes of Health, Department of Health and Human Services. No competing interests are declared. Trial registration number: N/A.

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... Cigarette smoking has multiple effects on hormone secretion, mainly mediated by the pharmacological action of nicotine and by toxins such as thiocyanate (Kapoor and Jones 2005). It has been shown that women who smoke are more likely to experience menopause between 1 and 2 years earlier than non-smokers ( Moderate physical activity has been associated with later age at natural menopause (Schoenaker et al 2014) in some studies, while others observed no association for either adolescence or adulthood physical activity (Zhao et al 2018). ...
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Chapter
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In a cohort of 19,731 Norwegian postmenopausal women, the authors analyzed relations between the age at natural menopause and all-cause mortality. A total of 18,533 women died during the 37 years of follow-up from 1961 to 1997. An inverse relation was found between the age at menopause and the all-cause mortality rate (p = 0.003). The strength of the association was moderate, however, with 1.6% (95% confidence interval: 0.6, 2.7) reduced mortality per 3 years' increase in age at menopause. The impact appeared to be stronger in women with an attained age of less than 70 years (3.7% reduction in risk) than in women aged 80 years or more (1.0%). The inverse relation could not be explained by extreme mortality rates in women with very early (<40 years) or late (>55 years) menopause or by possible confounding variables like birth cohort, place of residence, occupational category (own or husband's occupation), body mass index, age at menarche, and first and last delivery or parity. The smoking prevalence was low in the underlying population, and the use of hormone replacement therapy was very rare. The authors conclude that age at natural menopause is inversely related to all-cause mortality.
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In a cross-sectional study of 157 Turkish women attending outpatient clinics of a university hospital during April-May 2003, association between various subject characteristics and menopause timing was investigated. Characteristics were self-reported by women aged 45-60. Of the lifestyle factors, sun exposure, physical activity, food intake and dressing with headscarf were obtained as recalled average lifelong practices up to time of menopause. Cox proportional hazard modeling was used, censoring for hysterectomy, oopherectomy and HRT use. Median age at natural menopause was 52 years. In multivariate analysis, earlier natural menopause was associated with low level of lifelong sun exposure (HR=6.381, 95% CI: 2.996-13.588, p< or =0.0001), heavy physical activity (HR=2.335, 95% CI: 1.305-4.177, p=0.0043), current calcium supplement use (HR=3.191, 95% CI: 1.361-7.485, p=0.0076), diagnosis of hypertension (HR=2.002, 95% CI: 1.186-3.378, p=0.0093), not owning a house (HR=3.002, 95% CI: 1.148-7.852, p=0.0250) and longer years on oral contraceptives (HR=1.085, 95% CI: 1.000-1.176, p=0.0487). Engagement in farming (HR=2.043, 95% CI: 1.056-3.952, p=0.0339), height (cm) (HR=0.953, 95% CI: 0.907-0.994, p=0.0279) and fish consumption (servings/week) (HR=0.600, 95% CI: 0.375-0.960, p=0.0331) were associated with age at menopause in univariate analysis only. For n=109 women who recalled whether maternal menopausal age was <50 or > or =50, sun exposure (HR=7.221, 95% CI: 2.971-17.547, p<0.0001) was a stronger predictor of age at natural menopause than maternal menopausal age (HR=2.882, 95% CI: 1.477-5.621, p=0.0019). We identify some previously unrecognized correlates of age at natural menopause, namely self-reported lifelong sun exposure, lifelong physical activity, house-ownership, current use of calcium supplements, and lifelong fish consumption. These findings should be confirmed in larger studies.
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The purpose of this study was to evaluate the relationship between certain reproductive and lifestyle factors and the occurrence of early natural menopause. A case/control study was conducted on a basal population of 2510 women participating in the "Mexican Institute of Social Security health workers cohort study". Cases were defined as those women for whom natural menopause presented by age 47. Information was obtained through a self-administered questionnaire. The risk of early menopause is associated with short menstrual cycles [<26 days, OR = 3.79 (IC 95% 1.37-10.52)], a short period of oral contraceptives use [<1 year, OR = 2.63 (IC 95% 1.10-6.29)], a lower number of pregnancies [<2, OR = 1.63 (IC 95% 1.03-2.57)], low body mass index [< or =27 kg/m2, OR = 1.64 (IC 95% 1.10-2.43)], low schooling level [<6 years, OR = 3.02 (IC 95% 1.26-7.23)], smoking history [>15 cigarettes/day, OR = 2.7 (IC 95% 1.00-7.30)], and birth cohorts [> or =950, OR = 4.09 (IC 95% 2.62-6.39)]. The findings of this study suggest that both reproductive and lifestyle factors are significant elements in the occurrence of early menopause in Mexican women.
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Early onset of menopause is a risk factor for several health problems. The objective was primarily to investigate the association between early menopause and current, past active and passive smoking. A second aim was to investigate the association between coffee and alcohol consumption and early menopause. The present population-based cross-sectional study included a sub-sample of 2123 postmenopausal women born in 1940-41 who participated in the Oslo Health Study. Early menopause was defined as menopause occurring at an age of less than 45 years. We applied logistic regression analyses (crude and adjusted odds ratio (OR)) to examine the association between early menopause and selected lifestyle factors. Current smoking was significantly associated with early menopause (adj. OR, 1.59; 95% CI, 1.11-2.28). Stopping smoking more than 10 years before menopause considerably reduced the risk of early menopause (adj. OR, 0.13; 95% CI, 0.05-0.33). Total exposure to smoking (the product of number of cigarettes per day and time as a smoker) was positively related to early menopause and, at the highest doses, nearly doubled the odds (adj. OR, 1.93; 95% CI, 1.12-3.30). These data suggest a possible dose-response relationship between total exposure to smoking and early menopause, but no dose-response relationship was detected for the other variables examined. We found no significant association of coffee or alcohol consumption with early menopause. Of the lifestyle factors tested, high educational level (adj. OR, 0.50; 95% CI, 0.34-0.72) and high social participation (adj. OR, 0.60, 95% CI, 0.39-0.98) were negatively associated with early menopause. This cross-sectional study shows an association between current smoking and early menopause. The data also suggest that the earlier a woman stops smoking the more protected she is from early menopause. Early menopause was not significantly associated with passive smoking, or alcohol or coffee consumption.
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Reproductive characteristics play an aetiological role for many diseases, including reproductive cancers. They have been shown to vary internationally and nationally, but have not yet been described for the whole Swiss population. The study investigated the variability of reproductive characteristics, their patterns, and main determinants across a population-based female study population in Switzerland. Reproductive characteristics obtained from 3119 women (28-72 years) participating in the SAPALDIA cohort survey in 2001-2003 are described across birth cohorts, study areas, language regions, and levels of urbanization. Determinants of age at menopause were analysed by Cox regression. Reported median age at menarche was 13 years and median age at natural menopause was 52 years. The prevalence of nulliparity was 27%, and the fertility rate 1.6. Across birth cohorts there was a decline of menarcheal age and fertility rates, and an increase of nulliparity and age at last pregnancy. All characteristics varied across study areas, language regions, and levels of urbanization. Smoking, parity, and physical exercise were stronger predictors of earlier (<52 years) than older (>52 years) menopausal age. Reproductive events show secular and geographic variation within Switzerland. Smoking, parity and physical activity significantly predict age at natural menopause, particularly before age 52. The secular trend of earlier menarche and increased nulliparity may result in a higher risk of reproductive cancers in younger generations.
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Physical activity has been consistently associated with lower risk of postmenopausal breast cancer, but its relationship with premenopausal breast cancer is unclear. We investigated whether physical activity is associated with reduced incidence of premenopausal breast cancer, and, if so, what age period and intensity of activity are critical. A total of 64,777 premenopausal women in the Nurses' Health Study II reported, starting on the 1997 questionnaire, their leisure-time physical activity from age 12 to current age. Cox regression models were used to examine the relationship between physical activity, categorized by age period (adolescence, adulthood, and lifetime) and intensity (strenuous, moderate, walking, and total), and risk of invasive premenopausal breast cancer. During 6 years of follow-up, 550 premenopausal women developed breast cancer. The strongest associations were for total leisure-time activity during participants' lifetimes rather than for any one intensity or age period. Active women engaging in 39 or more metabolic equivalent hours per week (MET-h/wk) of total activity on average during their lifetime had a 23% lower risk of premenopausal breast cancer (relative risk = 0.77; 95% confidence interval = 0.64 to 0.93) than women reporting less activity. This level of total activity is equivalent to 3.25 h/wk of running or 13 h/wk of walking. The age-adjusted incidence rates of breast cancer for the highest (> or = 54 MET-h/wk) and lowest (< 21 MET-h/wk) total lifetime physical activity categories were 136 and 194 per 100 000 person-years, respectively. High levels of physical activity during ages 12-22 years contributed most strongly to the association. Leisure-time physical activity was associated with a reduced risk for premenopausal breast cancer in this cohort. Premenopausal women regularly engaging in high amounts of physical activity during both adolescence and adulthood may derive the most benefit.
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Study question: Is adult adiposity associated with early menopause? Summary answer: Overall and abdominal adiposity were non-linearly associated with odds for early natural menopause with elevated odds observed among women who were underweight in early or mid-adulthood compared to lean-normal weight women. What is known already: High and low adiposity have been associated with reproductive function and may potentially impact timing of menopause. It is unclear whether various aspects of adiposity are associated with risk of early menopause. Study design, size, duration: Prospective cohort study that examined data from 78 759 premenopausal women from the Nurses' Health Study II who were followed from 1989 to 2011 for incidence of early natural menopause. Participants/materials, setting, methods: Participants were aged 25-42 years and premenopausal at baseline in 1989, when information on menopausal status, height and weight was reported via questionnaire. Information on menopausal status, type of menopause (natural, surgical, radiation/chemotherapy), hormone therapy use and weight was updated every two years along with information on smoking, physical activity and other behavioral and health-related factors. Multivariable logistic regression was used to estimate odds ratios for early menopause, defined as natural menopause before age 45 years, by aspects of adiposity. Main results and the role of chance: Early natural menopause was reported by 2804 participants. Body mass index (BMI) was non-linearly associated with risk for early menopause. Compared to women with BMI = 18.5-22.4 kg/m2, those with BMI < 18.5 kg/m2 had a significant 30% higher odds of early menopause (95% confidence interval (CI) = 1.08, 1.57), while women with BMIs between 25.0-29.9 kg/m2 had significant 21-30% lower odds. Odds were not higher in women with BMI ≥ 35.0 kg/m2 in fully adjusted analysis. Non-linear associations with higher odds in underweight women were also observed for age 18 and age 35 BMI, though lower odds for overweight women was only observed for age 35 BMI. Odds were highest among women with age 18 BMI < 18.5 kg/m2 reporting severe weight cycling. Limitations, reasons for caution: Though weight and early menopause status were self-reported, validation studies conducted among Nurses' Health Study participants suggest that self-reported weight is highly correlated with directly measured weight, and prospective self-reported menopausal status is highly reproducible. It is possible that underweight women may have been misclassified with an earlier age at menopause if being underweight led to amenorrhea. Wider implications of the findings: In one of the few studies to prospectively examine a variety of adiposity measures and risk for early menopause, our findings that women who were underweight in early or mid-adulthood had elevated risk for early menopause can assist in efforts to better understand the etiology of early menopause. Additional prospective research is needed to understand how low adiposity may physiologically impact timing of menopause. Study funding/competing interest(s): This study was conducted with funding from NIH UM1CA176726 and R01HD078517. The authors declare no conflicts of interest. Trial registration number: Not applicable.
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Menopause before age 45 affects roughly 5%-10% of women and is associated with higher risk of adverse health conditions. Smoking may increase early menopause risk; however, evidence is inconsistent, and data regarding smoking amount, duration, cessation and patterns over time and risk are scant. We used data from the Nurses' Health Study II of 116,429 nurses from 1989 through 2011 and Cox proportional hazards models to estimate hazard ratios (HR) adjusting for confounders. Compared to never-smokers, current smokers had a HR of 1.90 (95% CI: 1.71, 2.11); former smokers had a HR of 1.10 (95% CI: 1.00, 1.21). Increased risks were observed among women reporting current smoking with a HR = 1.72 (95% CI: 1.36, 2.18) for 11-15 pack-years; HR = 1.72 (95% CI: 1.38, 2.14) for 16-20 pack-years; and HR = 2.42 (95% CI: 2.11, 2.77) for >20 pack-years. Elevated risk was observed in former smokers reporting 11-15 (HR = 1.29, 95% CI: 1.07-1.55), 16-20 (HR = 1.42, 95% CI: 1.13, 1.79) or >20 pack-years (HR = 1.54, 95% CI: 1.23, 1.93). Women who smoked ≤10 cigarettes/day but quit by age 25 had comparable risk to never-smokers (HR = 1.03, 95% CI: 0.91, 1.17). A dose-response relation between smoking and early natural menopause risk, and reduced risk among quitters, may provide insights into the mechanisms of cigarette smoking on reproductive health.
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The aim of this study was to evaluate the reproducibility and validity of a 61-item semiquantitative food frequency questionnaire used in a large prospective study among women. This form W88 administered twice to 173 particIpants at an interval of approximate'y one year (1980-1981), and four one-week diet records for each subject were collected during that period. Intraclass correlation coeffidents for nutrient intakes estimated by the one-week diet records (range = 0.41 for total Vitamin A without supplements to 0.79 for Vitamin B, with supplements) were similar to those computed from the questionnaire (range = 0.49 for total Vitamin A without 8upplements to 0.71 for sucrose), indicating that these methods were generally comparable with respect to reproducibility. With the exception of sucrose and total carbohydrate, nutilent Intakes from the diet records tended to correlate more strongly with those computed from the questionn&re after adjustment for total caloric Intake. Correlation coefficients between the mean calorie-adjusted intakes from the four one-week diet records and those from the questionna ire completed after the diet records ranged from 0.36 for Vitamin A without supplements to 0.75 for vitamin C with supplements. Overall, 48% of 8ubjects n the lowest quintile of calorie-Adjusted intake computed from the diet records were also in the lowest questionnaire quintile, and 74% were in the lowest one of two questionnaire quintiles. SImilarly, 49% of those in the highest diet record quintile were also in the highest questionnaire quintile, and 77% were In the highest one or two questionnafre quintiles. These data indicate that a simple self-administered dietary questionnaire can provide u8efuI information about indMdual nutrient intakes over a one-year penod.
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Early menopause, the cessation of ovarian function prior to age 45, affects 5-10% of Western women and is associated with an increased risk of adverse health outcomes. Literature suggests that high vegetable protein intake may prolong female reproductive function. We evaluated the relation of long-term intake of vegetable protein, animal protein, and specific protein-rich foods with incidence of early natural menopause in the Nurses' Health Study II cohort. Women included in analyses (n = 85,682) were premenopausal at baseline (1991) and followed until 2011 for onset of natural menopause. Protein intake was assessed via food frequency questionnaire. In Cox proportional hazard models adjusting for age, smoking, body mass index, and other factors, women in the highest quintile of cumulatively-averaged vegetable protein intake (median: 6.5% of calories) had a significant 16% lower risk of early menopause compared to women in the lowest quintile (3.9% of calories; 95% confidence interval: 0.73-0.98; P-trend: 0.02). Intakes of specific foods including pasta, dark bread and cold cereal were also associated with lower risk (P < 0.05). Conversely, animal protein intake was unrelated to risk. High consumption of vegetable protein, equivalent to 3-4 servings per day of protein-rich foods, is associated with lower incidence of early menopause in US women.
Article
Background: Early menopause, defined as the cessation of ovarian function before the age of 45 y, affects ∼10% of women and is associated with higher risk of cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk factors for early menopause have been identified, but emerging data suggest that high vitamin D intake may reduce risk. Objective: We evaluated how intakes of vitamin D and calcium are associated with the incidence of early menopause in the prospective Nurses’ Health Study II (NHS2). Design: Intakes of vitamin D and calcium from foods and supplements were measured every 4 y with the use of a food-frequency questionnaire. Cases of incident early menopause were identified from all participants who were premenopausal at baseline in 1991; over 1.13 million person-years, 2041 women reported having natural menopause before the age of 45 y. We used Cox proportional hazards regression to evaluate relations between intakes of vitamin D and calcium and incident early menopause while accounting for potential confounding factors. Results: After adjustment for age, smoking, and other factors, women with the highest intake of dietary vitamin D (quintile median: 528 IU/d) had a significant 17% lower risk of early menopause than women with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95); P-trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246 mg/d) compared with the lowest (median: 556 mg/d) was associated with a borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76, 1.00; P-trend = 0.03). Associations were stronger for vitamin D and calcium from dairy sources than from nondairy dietary sources, whereas high supplement use was not associated with lower risk. Conclusions: Findings suggest that high intakes of dietary vitamin D and calcium may be modestly associated with a lower risk of early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations, other dairy constituents, and early menopause are warranted.
Article
A heterogeneous disorder, premature menopause is not an uncommon entity, affecting approximately 1% of women younger than 40 years. Multisystem implications are recognized as sequelae to the premature deprivation of ovarian steroids, posing unique health-related challenges in this population. An integrated management approach that addresses both the physical and psychological health concerns and the overall well-being of this relatively chronologically young population is paramount. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
A prospective study was conducted in Takayama, Gifu, Japan, to evaluate the association between diet and the onset of menopause. A total of 1,130 female residents aged 35-54 years who were premenopausal and completed a validated semiquantitative food frequency questionnaire in 1992 were contacted by mail with a follow-up questionnaire in 1998 to update information on menopause. Onset of menopause was defined as a woman's age at the last menstrual period prior to stopping menstruation for 12 months. During the 6-year study period, 296 women experienced natural menopause. The Cox proportional hazards model was used to estimate hazard ratios of the onset of menopause after controlling for age, total energy, body mass index, years of smoking, and age at which regular menstrual cycle began. The authors found that green and yellow vegetable intake was significantly inversely associated with the 6-year incidence of menopause (hazard ratio = 0.71, 95% confidence interval: 0.54, 0.95 for the highest vs. lowest tertile of intake, p for trend = 0.02). Association of carotene intake with the incidence of menopause was of borderline significance (hazard ratio = 0.78, 95% confidence interval: 0.59, 1.04, p for trend = 0.07).
Article
Objective: The menopausal transition is associated with an increase in risk for cardiovascular disease; however, whether variability in reproductive aging relates to cardiovascular risk factors in the premenopausal period has not been studied. Methods: In a multiethnic sample of 951 healthy, regularly cycling women aged 25 to 45 years (mean [SD] age, 35.2 [5.5] y), we examined antimüllerian hormone (AMH), a validated marker of ovarian reserve, in relation to the overall number of cardiometabolic risk factors, calculated as the sum of the five components of metabolic syndrome (triglycerides ≥150 mg/dL; high-density lipoprotein <50 mg/dL; homeostasis model assessment of insulin resistance ≥2.6; waist circumference equal to or higher than race-specific cutoff; and hypertensive [vs normotensive] status), and in relation to each of these risk factors individually. Results: In age-adjusted models, results showed that the number of cardiometabolic risk factors was 52.1% higher among women with low versus high AMH levels and 46.0% higher among women with mid versus high AMH levels. In addition, results showed that low and mid levels of AMH (vs high) were associated with an increase in risk with respect to high-density lipoprotein (odds ratio [OR], 1.814; 95% CI, 1.211-2.718 and OR, 1.568; 95% CI, 1.083-2.269, respectively), waist circumference (OR, 2.012; 95% CI, 1.380-2.934 and OR, 1.881; 95% CI, 1.333-2.654, respectively), and hypertensive status (OR, 2.373; 95% CI, 1.095-5.143 and OR, 2.052; 95% CI, 0.976-4.314, respectively) outcomes. Associations, however, attenuated when body mass index was covaried (Ps > 0.05). Conclusions: Cross-sectional evidence suggests that having a greater ovarian reserve is associated with having a healthier cardiometabolic risk factor profile. Future longitudinal studies are needed to determine whether this association may be mediated by body mass index.
Article
Although physical activity modulates the hypothalamic-pituitary-ovarian axis, the few studies that have investigated whether physical activity is associated with age at natural menopause have yielded mixed results. We set out to determine whether physical activity is associated with the timing of natural menopause in a large cohort of California women overall and by smoking history. We investigated the association between long-term physical activity (h/wk/y) and age at natural menopause among 97,945 women in the California Teachers Study. Multivariable Cox proportional hazards regression methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The impact of cigarette smoking (never smoker, former light smoker, former heavy smoker, current light smoker, and current heavy smoker) as an effect modifier was evaluated. In a multivariable model adjusted for body mass index at age 18 years, age at menarche, race/ethnicity, and age at first full-term pregnancy, increased physical activity was statistically significantly associated with older age at natural menopause (Ptrend = 0.005). Higher body mass index at age 18 years (Ptrend = 0.0003) and older age at menarche (Ptrend = 0.0003) were also associated with older age at natural menopause. Hispanic ethnicity (vs non-Hispanic whites; HR, 1.17; 95% CI, 1.09-1.26), current smokers (vs never smokers; HR, 1.68; 95% CI, 1.60-1.75 for current light smokers; HR, 1.38; 95% CI, 1.33-1.44 for current heavy smokers), and older age at first full-term pregnancy (HR≥29, 2+ full-term pregnancies vs HR<29, 2+ full-term pregnancies, 1.10; 95% CI, 1.06-1.14) were associated with earlier age at natural menopause. Upon stratification by smoking history, increased physical activity was statistically significantly associated with older age at natural menopause among heavy smokers only (HRhighest quartile vs HRlowest quartile, 0.88; 95% CI, 0.81-0.97; Ptrend = 0.02 for former heavy smokers; HRhighest quartile vs HRlowest quartile, 0.89; 95% CI, 0.80-0.99; Ptrend = 0.04 for current heavy smokers). Age at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.
Article
Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if self-reported early menopause (menopause at an age <46 y) identifies women as at risk for future coronary heart disease or stroke. The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46 y) and future coronary heart disease and stroke was assessed in 2,509 women (ages 45-84 y; 987 white, 331 Chinese, 641 black, and 550 Hispanic) from the Multi-ethnic Study Atherosclerosis who were free of cardiovascular disease at baseline. Of 2,509 women, 693 (28%) reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank P = 0.008 and P = 0.0158). In models adjusted for age, race/ethnicity, Multi-ethnic Study Atherosclerosis site, and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (hazard ratio, 2.08; 95% CI, 1.17-3.70; and hazard ratio, 2.19; 95% CI, 1.11-4.32, respectively). Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors.
Article
Physical activity has many health benefits. Although greater activity has been related to lower postmenopausal breast cancer risk, important details remain unclear, including type, intensity, and timing of activity and whether the association varies by subgroups. Within the prospective Nurses' Health Study, we assessed the associations of specific and total activity, queried every 2 to 4 years since 1986, with breast cancer risk. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Activity was measured as hours of metabolic equivalent task values (MET-h). During 20 years of follow-up (1986-2006), 4782 invasive breast cancer cases were documented among 95 396 postmenopausal women. Compared with less than 3 MET-h/wk (<1 h/wk walking), women engaged in higher amounts of recent total physical activity were at lower breast cancer risk (≥27 MET-h/wk [approximately 1 h/d of brisk walking]: HR, 0.85; 95% CI, 0.78-0.93; P < .001 for trend). Compared with women who were least active at menopause and through follow-up (<9 MET-h/wk [approximately 30 minutes of walking at an average pace on most days of the week]), women who increased activity were at lower risk (<9 MET-h/wk at menopause and ≥9 MET-h/wk during follow-up: HR, 0.90; 95% CI, 0.82-0.98). Among specific activities modeled simultaneously, brisk walking was associated with lower risk (per 20 MET-h/wk [5 h/wk]: HR, 0.91; 95% CI, 0.84-0.98). The association with total activity did not differ significantly between estrogen and progesterone receptor-positive and -negative tumors (P = .65 for heterogeneity). Our findings suggest that moderate physical activity, including brisk walking, may reduce postmenopausal breast cancer risk and that increases in activity after menopause may be beneficial.
Article
To review and summarize current evidence on the health consequences of premature menopause and early menopause. We reviewed existing literature and combined graphically some results from the Mayo Clinic Cohort Study of Oophorectomy and Aging. Premature menopause or early menopause may be either spontaneous or induced. Women who experience premature menopause (before age 40 years) or early menopause (between ages 40 and 45 years) experience an increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other sequelae. The risk of adverse outcomes increases with earlier age at the time of menopause. Some of the adverse outcomes may be prevented by estrogen treatment initiated after the onset of menopause. However, estrogen alone does not prevent all long-term consequences, and other hormonal mechanisms are likely involved. Regardless of the cause, women who experience hormonal menopause and estrogen deficiency before reaching the median age of natural menopause are at increased risk for morbidity and mortality. Estrogen treatment should be considered for these women, but may not eliminate all of the adverse outcomes.
Article
The aim of this study was to evaluate the reproducibility and validity of a 61-item semiquantitative food frequency questionnaire used in a large prospective study among women. This form was administered twice to 173 participants at an interval of approximately one year (1980-1981), and four one-week diet records for each subject were collected during that period. Intraclass correlation coefficients for nutrient intakes estimated by the one-week diet records (range = 0.41 for total vitamin A without supplements to 0.79 for vitamin B6 with supplements) were similar to those computed from the questionnaire (range = 0.49 for total vitamin A without supplements to 0.71 for sucrose), indicating that these methods were generally comparable with respect to reproducibility. With the exception of sucrose and total carbohydrate, nutrient intakes from the diet records tended to correlate more strongly with those computed from the questionnaire after adjustment for total caloric intake. Correlation coefficients between the mean calorie-adjusted intakes from the four one-week diet records and those from the questionnaire completed after the diet records ranged from 0.36 for vitamin A without supplements to 0.75 for vitamin C with supplements. Overall, 48% of subjects in the lowest quintile of calorie-adjusted intake computed from the diet records were also in the lowest questionnaire quintile, and 74% were in the lowest one of two questionnaire quintiles. Similarly, 49% of those in the highest diet record quintile were also in the highest questionnaire quintile, and 77% were in the highest one or two questionnaire quintiles. These data indicate that a simple self-administered dietary questionnaire can provide useful information about individual nutrient intakes over a one-year period.
Article
The reproducibility and validity of self-administered questionnaires on physical activity and inactivity were examined in a random (representative) sample of the Nurses' Health Study II cohort and a random sample of African-American women in that cohort. Repeat questionnaires were administered 2 years apart. Past-week activity recalls and 7-day activity diaries were the referent methods; these instruments were sent to participants four times over a 1-year period. The 2-year test-retest correlation for activity was 0.59 for the representative sample (n = 147) and 0.39 for the African-American sample (n = 84). Correlations between activity reported on recalls and that reported on questionnaire were 0.79 and 0.83 for the representative and African-American samples, respectively. Correlations between activity reported in diaries and that reported on questionnaire were 0.62 and 0.59, respectively. Test-retest coefficients for inactivity were 0.52 and 0.55, respectively. Correlations between inactivity reported in diaries and that reported on questionnaire were 0.41 and 0.44, respectively. The simple, short questionnaires on activity and inactivity used in the Nurses' Health Study II are reasonably valid measures for epidemiological research.
Article
To investigate possible social, lifestyle-related and biological predictors of early menopause in middle-aged women, followed prospectively for 11 years. A prospective, population-based, cohort follow-up, observational study. Glostrup Hospital, Copenhagen, Denmark. A total of 493 female subjects, all aged 40 years at baseline, and divided into three groups according to self-reported menopausal age (40-45, 46-51, 51+ years), after 12 months of amenorrhoea. Women having had medical or surgical interventions to influence menopausal state were excluded. Body mass index, glucose, insulin, lipids, creatinine, uric acid, thyroid-stimulating hormone (TSH), lung function tests (forced VC, FEV1, peak flow), blood pressure; a self-administered questionnaire with questions on psychosocial variables, lifestyle, and self-rated health. An early menopausal age correlated in an univariate way with impaired lung function, increased smoking habits and low social class (in childhood or present), as well as with a feeling of tiredness, all measured at the baseline investigation. On the contrary, a later menopausal age correlated with higher serum insulin and uric acid levels. In multiple regression analysis, with menopausal age as the dependent variable, it was found that smoking habits (number of years smoking) was inversely (P < 0.001), and insulin as well as uric acid were positively (P < 0.05) correlated with menopausal age. Females who smoke run an increased risk of early menopause, whereas relative hyperinsulinaemia is independently associated with later menopause. At the age of 40 years, high insulin levels in females might be just a marker for normal female sex hormone physiology, not for insulin resistance, as seen in postmenopausal female subjects. Early menopause might be useful as a potential model of premature ageing.
Article
A prospective study was conducted in Takayama, Gifu, Japan, to evaluate the association between diet and the onset of menopause. A total of 1,130 female residents aged 35-54 years who were premenopausal and completed a validated semiquantitative food frequency questionnaire in 1992 were contacted by mail with a follow-up questionnaire in 1998 to update information on menopause. Onset of menopause was defined as a woman's age at the last menstrual period prior to stopping menstruation for 12 months. During the 6-year study period, 296 women experienced natural menopause. The Cox proportional hazards model was used to estimate hazard ratios of the onset of menopause after controlling for age, total energy, body mass index, years of smoking, and age at which regular menstrual cycle began. The authors found that green and yellow vegetable intake was significantly inversely associated with the 6-year incidence of menopause (hazard ratio = 0.71, 95% confidence interval: 0.54, 0.95 for the highest vs. lowest tertile of intake, p for trend = 0.02). Association of carotene intake with the incidence of menopause was of borderline significance (hazard ratio = 0.78, 95% confidence interval: 0.59, 1.04, p for trend = 0.07).
Article
This study assessed predictors of the onset of natural menopause in African American women. We used mailed questionnaires to collect data at baseline in 1995 and during follow-up from Black Women's Health Study participants. Cox proportional hazards regression was used to assess potential predictors-including experiences of racism-of the onset of natural menopause among 17 070 women aged 35 to 55 years and premenopausal in 1995. The hazard ratio (HR) was 1.43 for current smokers (95% confidence interval [CI] = 1.24, 1.66) and 1.21 (95% CI = 1.06, 1.38) for ex-smokers and significantly less for obese women and oral contraceptive users. Hazard ratios for most questions about racism were elevated by 10% to 30% but were not statistically significant. Earlier onset of natural menopause among African American women is strongly associated with smoking and inversely associated with body mass index and oral contraceptive use.
Article
The aim of this study was primarily to determine the relationship between early menopause and the presence of fractures later in life, and secondly, to check for the significance of confounding factors (such as smoking habits, body mass index (BMI), weight and use of hormones). In this cross-sectional population based study, the subjects were 4725 postmenopausal women, 50-80 years of age, registered with 23 general practitioners (GPs). For the purpose of the present study, the total population was analyzed as well as the subgroup of 2757 women (the study population) with a natural menopause. Medical history questionnaire, weight, height and bone mineral density measurements were taken. Bivariate and multivariate analyses were carried out with documented fractures in three categories: during lifetime; after menopause and after age 50 years) as dependent variable and age, BMI, bone mineral density, weight, smoking habits, use of hormones and early menopause as independent variables. The total study population as well as the subgroups "early" and "normal menopause", stratified in three 10-year and in six 5-year categories, were analyzed. Results are expressed as odds ratio and 95% confidence intervals (CI). Multivariate logistic regression analysis revealed that over 70 years of age, BMD< or =0.800 ( t-score<2.5) and early menopause were the only systemic independent predictors of all three fracture categories. Comparing the subgroups normal menopause and early menopause, the early menopause group showed a statistically significant higher overall fracture rate (OR=1.5; CI 1.2-1.8). Over age 70, the difference in the prevalence of fractures reached statistical significance in each age category (OR: 1.8 and 2.1, respectively). Smoking was found to be associated with early menopause (OR=1.5; CI 1.2-1.8) but not with the presence of fractures. Height above 165 cm was found to be associated with a higher prevalence of fractures during lifetime. The present study shows that early menopause is statistically significant associated with the presence of fractures during lifetime, after age 50 years and after menopause. Especially at older age, early menopause is an important predictor of fractures.
Article
The aim of the study was to explore the influence of reproductive and dietary factors on the age at menopause. During follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort in Heidelberg (median duration 5.8 years), 1009 women experienced natural menopause. They were compared to 3798 women who did not experience menopause. Baseline dietary intake was obtained by means of validated food frequency questionnaires. Data on reproductive history and medication was collected by means of questionnaires. Cox' proportional hazard models were applied in order to identify determinants of the age at natural menopause. Increasing age at first full term pregnancy and a longer time interval until occurrences of regular menses are associated with later onset of natural menopause. Compared to never smokers, current smokers have the risk of younger age at menopause. High carbohydrate consumption and high intake of vegetable, fibre and cereal products are inversely related to the age at natural menopause. Women with higher intake of total fat, protein and meat experienced a delayed onset of natural menopause. Age at natural menopause is influenced by lifestyle and dietary factors. Further studies including biological markers are needed to clarify these associations.
Article
An association between physical activity and premenopausal breast cancer risk may be due, in part, to relationships with sex hormones or growth factors. Therefore, we assessed whether MET-h/week of total physical activity (moderate-to-vigorous intensity), walking, or vigorous physical activity, and h/week of standing or sitting were associated with plasma concentrations of several hormones. We examined levels of estrogens, androgens, progesterone, prolactin, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), IGF binding protein-3, and growth hormone (GH) in 565 premenopausal women, ages 33-52 years, from the Nurses' Health Study II (NHSII). About 87% of women had both timed follicular and luteal samples; other women had one untimed sample. In general we observed few associations between sex hormone or IGF levels and measures of physical activity or inactivity. However, free testosterone was modestly inversely associated with total physical activity (p-trend = 0.02). Luteal estradiol, free estradiol, and estrone also were inversely associated with total physical activity (p-trend = 0.10, 0.04, 0.01, respectively); however, the trend was substantially attenuated when excluding women with anovulatory cycles or irregular cycles. These cross-sectional results suggest that physical activity and inactivity have limited associations with premenopausal sex hormone and growth factor levels, except possibly luteal estrogens.
Article
Modifiable factors predicting the onset of menopause, a transition with important implications for women's health, have not been fully characterized. We evaluated the impact of dietary, lifestyle and reproductive factors on age at natural menopause and reproductive span in Chinese women. Study participants were Chinese women aged 40 to 70 who experienced natural menopause and participated in a population-based, prospective study, the Shanghai Women's Health Study (N = 33,054). Dietary intake at the baseline survey was assessed by food-frequency questionnaire. Regression (beta) coefficients, calculated by multivariable linear regression, were used to estimate the effects of dietary, lifestyle, and reproductive patterns on age at menopause and the number of reproductive years, adjusting for potential confounding factors. Early menarche, younger age at first live birth, older age at last live birth, longer duration of breast-feeding, and higher parity were associated with longer reproductive years (Ptrend < 0.01 for all). Higher body mass index at age 20, mid-life weight gain, and leisure-time physical activity during adolescence and adulthood predicted later menopause and longer reproductive span (Ptrend < 0.01 for all). Total intake of calories, fruits, and protein was positively associated with later menopause (Ptrend < 0.05 for all) and longer reproductive span (Ptrend < 0.05), except for carbohydrates (Ptre(nd) = 0.06), and long-term tea consumption predicted longer reproductive span (Ptrend = 0.03). Vegetable, fat, soy, and fiber intakes did not significantly affect reproductive span or age at menopause. Smoking was inversely associated with both early age at menopause and shorter reproductive span (Ptrend < 0.01). In addition to reproductive factors, intake of fruits and protein, smoking, tea consumption, lifetime patterns of physical activity, and weight gain influenced the onset of menopause and/or reproductive span in Chinese women.
Faculty of 1000 evaluation for Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis
  • Miller
Miller V. Faculty of 1000 evaluation for Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis. Menopause 2012;19:1081-1087.
Reproducibility and validity of self-reported menopausal status in a prospective cohort study
  • Colditz