Aina Emaus

17-beta-Estradiol in relation to age at menarche and adult obesity in premenopausal women

BACKGROUND We hypothesize that premenopausal endogenous estradiol may be associated with age at menarche and adult overweight and obesity, potentially contributing to breast cancer risk. METHODS We assessed age at menarche by questionnaire among 204 healthy Norwegian women, aged 25-35 years. Measures of body composition included body mass index (BMI, kg/m(2)), waist circumference (WC, cm), waist-to-hip ratio (WHR) and fat percentage dual energy X-ray absorptiometry, (DEXA). Daily salivary 17-beta-estradiol (E(2)) concentrations were collected throughout one entire menstrual cycle and assessed by radioimmunoassay (RIA). Linear regression analyses and linear mixed models for repeated measures were used and potential confounding factors and effect modifiers were tested. RESULTS Among women with an early age at menarche (< or =12 years), the overall mean salivary E(2) concentration increased by 3.7 pmol/l (95% confidence interval, 1.8-5.7 pmol/l) with each 9.8 cm (1 SD) increase in WC, which represents a 20.7% change in the mean for the total group. Among the same early maturers, a 1 SD (0.06) change in WHR was directly associated with a 24.0% change in mean E(2) concentration for the total group. CONCLUSIONS Our findings support the hypothesis that early age at menarche, together with adult overweight and obesity, result in high levels of 17-beta-estradiol throughout the menstrual cycle.

Does a variation in self-reported physical activity reflect variation in objectively measured physical activity, resting heart rate, and physical fitness? Results from the Tromsø study

Aims: To study the association between self-reported physical activity (PA) and objectively measured PA, resting heart rate, and physical fitness. Methods: During 2007—08, 5017 men and 5607 women aged 30—69 years attended the sixth survey of the Tromsø study. Self-reported PA during leisure-time and work were assessed and resting heart rate was measured. In a sub-study, the activity study, PA (Actigraph LLC) and physical fitness (VO2max) were objectively measured among 313 healthy men and women aged 40—44 years. Results: Self-reported leisure PA was significantly correlated with VO2max (ml/kg/min) (women 0.40, p < 0.001, men 0.44 p < 0.001) and moderate-to-vigorous PA (>2000 counts/min) (women 0.28, p < 0.01, men 0.25, p < 0.01). The intra-class correlation coefficient between self-reported leisure PA and overall PA (counts/min) measured by accelerometer was 0.62 (95% CI 0.51, 0.71) for women and 0.59 (95% CI 0.47, 0.69) for men, and for VO2max the intra-class correlation coefficient was 0.86 (95% CI 0.81, 0.90) for both sexes. Among all participants, an inverse dose—response relationship was observed between self-reported leisure PA and resting heart rate for both men and women (p < 0.0001). More women than men met the international recommendations of 10,000 step counts/day (27% vs. 22%) and the recommendation of at least 30 minutes/day of moderate-to-vigorous intensities (30% vs. 22 %). Conclusions: The Tromsø physical activity questionnaire has acceptable validity and provides valid estimates of high-intensity leisure activity. However, these results underscore the need for collecting objectively PA measurements in large epidemiological studies.

Physical activity and lung cancer prevention.

Since lung cancer is among the cancers with the highest incidence and has the highest mortality rate of cancer worldwide, the means of reducing its impact are urgently needed. Emerging evidence shows that physical activity plays an etiological role in lung cancer risk reduction. The majority of studies support the fact that total and recreational physical activity reduces lung cancer risk by 20-30% for women and 20-50% for men, and there is evidence of a dose-response effect. The biological mechanisms operating between physical activity and lung cancer are likely complex and influenced by many factors including inherited or acquired susceptibility genes, gender, smoking, and other environmental factors. Several plausible biological factors and mechanisms have been hypothesized linking physical activity to reduced lung cancer risk including: improved pulmonary function, reduced concentrations of carcinogenic agents in the lungs, enhanced immune function, reduced inflammation, enhanced DNA repair capacity, changes in growth factor levels and possible gene-physical activity interactions. Future research should target the possible subgroup effects and the biologic mechanisms that may be involved.

Physical Activity, Heart Rate, Metabolic Profile, and Estradiol in Premenopausal Women

PURPOSE To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical activity (LPA), resting heart rate (HR), blood pressure (BP), anthropometry, and serum glucose, lipids, and insulin [Norwegian Energy Balance and Breast Cancer Aspect (EBBA) study]. E2 was measured in daily saliva samples throughout an entire menstrual cycle. A clustered metabolic risk score [z metabolic syndrome (zMS); total cholesterol-high-density lipoprotein-cholesterol (HDL-C) ratio, insulin resistance, total fat tissue, BP, and triglycerides] was defined. Linear regression and linear mixed models were used, and confounding factors were tested. RESULTS Physically active women had lower fat percentage (Ptrend = 0.003) and HRs (Ptrend = 0.003) than sedentary women. We estimated an increase in E2 of 1.27 pmol.L [95% confidence interval (CI), 0.06-2.47] for each 11.7 beats.min (1 SD) increase in HR, and this corresponds to the 7% change in mean concentration of E2 for the total group. Associations with E2 were also found for fat tissue, total cholesterol-HDL-C ratio, insulin resistance, and triglycerides. A dose-response relationship was observed among the three levels of LPA and HR and zMS (Ptrend = 0.03 for LPA; Ptrend = 0.004 for HR). Women in the highest tertile of the clustered metabolic risk score had average salivary E2profiles that were markedly higher, throughout the cycle, than those of the other groups, with a cycle peak-day difference in E2 of 22-28%. CONCLUSION LPA and HR were associated with metabolic risk score, and this score was associated with daily level of E2, pointing to important biologic mechanisms operating between a sedentary lifestyle and an increased breast cancer risk.

Duration of lactation, maternal metabolic profile, and body composition in the Norwegian EBBA I-study.

OBJECTIVE There is conflicting evidence as to whether duration of lactation may decrease the risk of subsequent development of an unfavorable maternal metabolic profile, including overweight and obesity. We hypothesized that duration of lactation is associated with a more favorable metabolic profile and healthier anthropometric measurements. SUBJECTS AND METHODS Ninety-eight parous women were studied from the Norwegian EBBAI-study (Energy Balance and Breast cancer Aspects-study), a cross-sectional study of healthy premenopausal women 25-35 years old. Historical lactation data were collected, anthropometric measurements were taken, fasting blood samples (for serum glucose, triglycerides, total cholesterol, and high-density lipoprotein cholesterol) were drawn, and women were asked to fill in a precoded food diary. RESULTS Mean time since last birth was 4.7 years, mean number of children was 1.9, mean total duration of lactation was 19 months, and average length of lactation per child was 10.3 months. Women who on average lactated for less than 10 months per child had higher mean levels of fasting serum glucose (5.2 mmol/L vs. 5.0 mmol/L, p=0.04), serum triglyceride (0.91 mmol/L vs. 0.66 mmol/L, p=0.001), and serum cholesterol (4.78 mmol/L vs. 4.32 mmol/L, p=0.004) and a higher waist-to-hip ratio (0.81 vs. 0.77, p=0.001) than women who lactated for 10 months or more per child. The inverse association between average length of lactation per child and waist-to-hip ratio persisted after adjustment for potential confounders. CONCLUSIONS These results support the hypothesis that duration of lactation may be associated with a healthier metabolic profile and healthier anthropometric measurements, especially lipid levels and waist-to-hip ratio, even years after weaning.

Adult Height, Insulin, and 17β-Estradiol in Young Women

Background: Adult height and insulin are thought to modify the development of breast cancer. However, little is known about the association between height and 17β-estradiol, a key factor in breast carcinogenesis, and whether insulin modifies such an association. Methods: Among 204 healthy women, ages 25 to 35 years, who participated in the Energy Balance and Breast Cancer Aspect I study, adult height (in centimeters) and fasting serum concentrations of insulin (pmol/L) were measured. 17β-Estradiol concentrations were measured in daily saliva samples throughout an entire menstrual cycle through RIA. Age and multivariate linear regression models were used to study the association between adult height and 17β-estradiol levels throughout an entire menstrual cycle and whether serum levels of fasting insulin may modify such an association. Results: The women had a mean age of 30.7 years, adult height of 166.9 cm, and serum insulin of 85.7 pmol/L. For each increase of one SD in insulin levels in the upper tertile of adult height, the adjusted level of 17β-estradiol increased by 3.1 pmol/L (95% confidence interval, 1.1-5.2), equivalent to a 17.3% higher mean average concentration of 17β-estradiol. Women with an adult height ≥170 cm (upper tertile) and insulin levels >101 pmol/L (upper quartile) experienced, on average, 41% higher 17β-estradiol levels throughout the entire menstrual cycle compared with women with the same adult height and insulin levels <101 pmol/L. Conclusion: Our findings support that premenopausal levels of 17β-estradiol vary in response to adult height and insulin levels, of possible importance for breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1477–83)

Ovarian hormones and reproductive risk factors for breast cancer in premenopausal women: the Norwegian EBBA-I study

BACKGROUND Ovarian hormones, parity and length of ‘menarche-to-first birth’ time interval are known risk factors for breast cancer, yet the associations between 17β-estradiol, progesterone and these reproductive factors remain unclear. METHODS A total of 204 women (25–35 years) who participated in the Norwegian EBBA-I study collected daily saliva samples for one complete menstrual cycle, and filled in a reproductive history questionnaire. Anthropometry was measured and saliva samples were analyzed for ovarian hormones. Associations between parity, the interval and ovarian hormones, and effects of hormone-related lifestyle factors were studied in linear regression models. RESULTS Mean age was 30.7 years, and age of menarche 13.1 years. Parous women had on average 1.9 births, and age at first birth was 24.5 years. No association was observed between parity and ovarian steroids. In nulliparous women, higher waist circumference (≥77.75 cm) and longer oral contraceptive (OC) use (≥3 years) were associated with higher levels of 17β-estradiol. Short (<10 years) versus long (>13.5 years) ‘menarche-to-first birth’ interval was associated with higher overall mean (Ptrend = 0.029), 47% higher maximum peak and 30% higher mid-cycle levels of 17β-estradiol. We observed a 2.6% decrease in overall mean salivary 17β-estradiol with each 1-year increase in the interval. CONCLUSIONS Nulliparous women may be more susceptible to lifestyle factors, abdominal overweight and past OC use, influencing metabolic and hormonal profiles and thus breast cancer risk. Short time between ‘menarche-to-first birth’ is linked to higher ovarian hormone levels among regularly cycling women, suggesting that timing of first birth is related to fecundity.

Low high-density lipoprotein cholesterol may signal breast cancer risk: recent findings and new hypotheses

Increasing bodyweight among women worldwide seems to be associated with a proportional rise in the number of women developing breast cancer. It is of utmost importance to obtain reliable biomarkers that may help clinicians to identify susceptible individuals among the growing population of women with excess adiposity. Our recent studies, reviewed within this article, support that adiposity-related metabolic disorders may represent high-risk phenotypes; specifically, we conclude that a low level of high-density lipoprotein cholesterol may be a reliable marker for breast cancer risk among overweight women. We tested our hypothesis among a large number of overweight women in the Norwegian Three County Cohort and the Norwegian cross-sectional study, the Energy Balance and Breast cancer Aspects (EBBA-I) study. Future studies should explore how genetic, environmental and behavioral factors may increase the susceptibility of overweight women to breast cancer, and how we can successfully establish targeted preventive strategies.

Increased long-term recreational physical activity is associated with older age at natural menopause among heavy smokers

ObjectiveAlthough 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. MethodsWe 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. ResultsIn 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). ConclusionsAge at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.

17β-Estradiol Levels During An Entire Menstrual Cycle In Response To Adult Stature and Insulin, Of Possible Importance For Breast Cancer Risk: The EBBA-I study.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #4078 Background: The normal breast cells develop into malignant cells as a result of a complex interplay between genetic, environmental, nutritional and hormonal factors. Attained adult stature and insulin levels, risk factors for breast cancer, may also vary in response to the same factors. Thus, we hypothesize that 17β-estradiol, a key factor in the carcinogenesis of the breast, may vary in response to adult height in combination with insulin levels of possible importance of breast cancer risk. Methods: Among 204 healthy women, aged 25-35 years who participated in the Norwegian EBBA-I study, 17β-estradiol concentrations were measured in daily saliva samples throughout one entire menstrual cycle using radioimmunoassay (RIA). Attained height (cm) was measured, and serum concentrations of insulin were determined in fasting blood samples. The associations between adult height, insulin and 17β-estradiol levels throughout a menstrual cycle were studied using multivariate linear regression analyses and linear mixed models for repeated measures. Adjustments for potential confounding factors were performed. Results: A 37.2 % increase in 17β-estradiol levels was observed during the entire menstrual cycle among women with an adult height ≥170 cm (upper tertile) and insulin levels ≥ 90 pmol/L (upper tertile) compared to women with the same attained adult height, and insulin levels < 90pmol/L. The association was even more pronounced when we looked into those women with attained adult height ≥170 cm (upper tertile) and serum insulin ≥ 101 pmol/L (upper quartile) (Fig. 1). Adjustments for potential confounding factors were performed. ![][1] Conclusion: Our findings support that premenopausal levels of 17β-estradiol vary in response to adult height and insulin levels, suggesting that women who become taller are put at risk for higher estradiol levels throughout the entire menstrual cycle when their insulin levels rise, of possible importance for breast cancer risk. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4078. [1]: /embed/graphic-1.gif