Pre-diagnostic high-sensitive C-reactive protein and breast cancer risk, recurrence, and survival.

Inflammation may initiate and promote breast cancer development, and be associated with elevated circulating levels of inflammation markers. A total of eight 130 initially healthy women, participated in the population-based Tromsø study (1994-2008). Pre-diagnostic high-sensitivity C-reactive protein (hs-CRP) was assessed. During 14.6 years of follow-up, a total of 192 women developed invasive breast cancer. These cases were followed for additional 7.2 years. Detailed medical records were obtained. We observed an overall positive dose-response relationship between pre-diagnostic hs-CRP and breast cancer risk (hazard ratio (HR) = 1.06, 95 % CI 1.01-1.11). Postmenopausal women with above median levels of hs-CRP (>1.2 mg/l) had a 1.42 (95 % CI 1.01-2.00) higher breast cancer risk compared to postmenopausal women with hs-CRP below median. Postmenopausal women, who were hormone replacement therapy non-users, and were in the middle tertile (0.8-1.9 mg/l), or highest tertile of hs-CRP (>1.9 mg/l), had a 2.31 (95 % CI 1.31-4.03) and 2.08 (95 % CI 1.16-3.76) higher breast cancer risk, respectively, compared with women in the lowest tertile. For each unit increase in pre-diagnostic hs-CRP levels (mg/l), we observed an 18 % increase in disease-free interval (95 % CI 0.70-0.97), and a 22 % reduction in overall mortality (95 % CI 0.62-0.98). Our study supports a positive association between pre-diagnostic hs-CRP and breast cancer risk. In contrast, increased pre-diagnostic hs-CRP was associated with improved overall mortality, but our findings are based on a small sample size, and should be interpreted with caution.

Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen and mammographic density phenotypes.

BACKGROUND: Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked to breast cancer development, and mammographic density is an established breast cancer risk factor. Whether there is an association between daily estradiol levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is unknown. METHODS: We assessed estradiol in daily saliva samples throughout an entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy Balance and Breast Cancer Aspects I study. DNA was genotyped using the Illumina Golden Gate platform. Mammograms were taken between days 7 and 12 of the menstrual cycle, and digitized mammographic density was assessed using a computer-assisted method (Madena). Multivariable regression models were used to study the association between SNPs in ESR1, premenopausal mammographic density phenotypes and daily cycling estradiol. RESULTS: We observed inverse linear associations between the minor alleles of eight measured SNPs (rs3020364, rs2474148, rs12154178, rs2347867, rs6927072, rs2982712, rs3020407, rs9322335) and percent mammographic density (p-values: 0.002-0.026), these associations were strongest in lean women (BMI, ≤23.6 kg/m2.). The odds of above-median percent mammographic density (>28.5 %) among women with major homozygous genotypes were 3-6 times higher than those of women with minor homozygous genotypes in seven SNPs. Women with rs3020364 major homozygous genotype had an OR of 6.46 for above-median percent mammographic density (OR: 6.46; 95 % Confidence Interval 1.61, 25.94) when compared to women with the minor homozygous genotype. These associations were not observed in relation to absolute mammographic density. No associations between SNPs and daily cycling estradiol were observed. However, we suggest, based on results of borderline significance (p values: 0.025-0.079) that the level of 17ß-estradiol for women with the minor genotype for rs3020364, rs24744148 and rs2982712 were lower throughout the cycle in women with low (<28.5 %) percent mammographic density and higher in women with high (>28.5 %) percent mammographic density, when compared to women with the major genotype. CONCLUSION: Our results support an association between eight selected SNPs in the ESR1 gene and percent mammographic density. The results need to be confirmed in larger studies.

Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies.

BACKGROUND: Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised. METHODS: We systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations. RESULTS: Eighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29-1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02-1.12) for overweight (BMI 25.0-<30.0) and 1.10 (95% CI 0.92-1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26-2.41) for pre-menopausal and 1.34 (95% CI 1.18-1.53) for post-menopausal breast cancer. For each 5 kg/m(2) increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 18%, 14%, and 29% for breast cancer mortality were observed, respectively. CONCLUSIONS: Obesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer.

A factor analysis approach to examining relationships among ovarian steroid concentrations, gonadotrophin concentrations and menstrual cycle length characteristics in healthy, cycling women.

STUDY QUESTION: How are ovarian steroid concentrations, gonadotrophins and menstrual cycle characteristics inter-related within normal menstrual cycles? SUMMARY ANSWER: Within cycles, measures of estradiol production are highly related to one another, as are measures of progesterone production; however, the two hormones also show some independence from one another, and measures of cycle length and gonadotrophin concentrations show even greater independence, indicating minimal integration within cycles. WHAT IS KNOWN ALREADY: The menstrual cycle is typically conceptualized as a cohesive unit, with hormone levels, follicular development and ovulation all closely inter-related within a single cycle. Empirical support for this idea is limited, however, and to our knowledge, no analysis has examined the relationships among all of these components simultaneously. STUDY DESIGN, SIZE, DURATION: A total of 206 healthy, cycling Norwegian women participated in a prospective cohort study (EBBA-I) over the duration of a single menstrual cycle. Of these, 192 contributed hormonal and cycle data to the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects provided daily saliva samples throughout the menstrual cycle from which estradiol and progesterone concentrations were measured. FSH and LH concentrations were measured in serum samples from three points in the same menstrual cycle and cycle length characteristics were calculated based on hormonal data and menstrual records. A factor analysis was conducted to examine the underlying relationships among 22 variables derived from the hormonal data and menstrual cycle characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Six rotated factors emerged, explaining 80% of the variance in the data. Of these, factors representing estradiol and progesterone concentrations accounted for 37 and 13% of the variance, respectively. There was some association between measures of estradiol and progesterone production within cycles; however, cycle length characteristics and gonadotrophin concentrations showed little association with any measure of ovarian hormone concentrations. LIMITATIONS, REASONS FOR CAUTION: Our summary measures of ovarian hormones may be imprecise in women with extremely long or short cycles, which could affect the patterns emerging in the factor analysis. Given that we only had data from one cycle on each woman, we cannot address how cycle characteristics may covary within individual women across multiple cycles. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are generalizable to other healthy populations with typical cycles, however, may not be applicable to cycles that are anovulatory, extreme in length or otherwise atypical. The results support previous findings that measures of estradiol production are highly correlated across the cycle, as are measures of progesterone production. Estradiol and progesterone concentrations are associated with one another, furthermore. However factor analysis also revealed more complex underlying patterns in the menstrual cycle, highlighting the fact that gonadotrophin concentrations and cycle length characteristics are virtually independent of ovarian hormones. These results suggest that despite integration of follicular and luteal ovarian steroid production across the cycle, cycle quality is a multi-faceted construct, rather than a single dimension. STUDY FUNDING/COMPETING INTEREST(S): The EBBA-I study was supported by a grant from the Norwegian Cancer Society (49 258, 05087); Foundation for the Norwegian Health and Rehabilitation Organizations (59010-2000/2001/2002); Aakre Foundation (5695-2000, 5754-2002) and Health Region East. The current analyses were completed under funding from the National Institutes of Health (K12 ES019852). No competing interests declared.

Prevalence and population structure of Staphylococcus aureus nasal carriage in healthcare workers in a general population. The Tromsø Staph and Skin Study.

Healthcare workers (HCWs) may be a reservoir for Staphylococcus aureus transmission to patients. We examined whether HCW status is associated with S. aureus nasal carriage and population structure (spa types) in 1302 women (334 HCWs) and 977 men (71 HCWs) aged 30-69 years participating in the population-based Tromsø Study in 2007-2008. Multivariable logistic regression models were used. While no methicillin-resistant S. aureus (MRSA) was isolated, overall, 26·2% of HCWs and 26·0% of non-HCWs were S. aureus nasal carriers. For women overall and women residing with children, the odds ratios for nasal carriage were 1·54 [95% confidence interval (CI) 1·09-2·19] and 1·86 (95% CI 1·14-3·04), respectively, in HCWs compared to non-HCWs. Moreover, HCWs vs. non-HCWs had a 2·17 and 3·16 times higher risk of spa types t012 and t015, respectively. This supports the view that HCWs have an increased risk of S. aureus nasal carriage depending on gender, family status and spa type.

Staphylococcus aureus nasal carriage is associated with serum 25-hydroxyvitamin D levels, gender and smoking status. The Tromsø Staph and Skin Study.

Vitamin D induces the expression of antimicrobial peptides with activity against Staphylococcus aureus. Thus, we studied the association between serum 25-hydroxyvitamin D (25(OH)D) and S. aureus nasal colonization and carriage. Nasal swabs, blood samples and clinical data from 2,115 women and 1,674 men, aged 30-87 years, were collected in the Tromsø Staph and Skin Study 2007-08, as part of the population-based sixth Tromsø Study. Multivariate logistic regression analyses were stratified by recognized risk factors for S. aureus carriage: sex, age and smoking. In non-smoking men, we observed a 6.6% and 6.7% decrease in the probability of S. aureus colonization and carriage, respectively, by each 5 nmol/l increase in serum 25(OH)D concentration (P < 0.001 and P = 0.001), and serum 25(OH)D > 59 nmol/l and ≥75 nmol/l as thresholds for ~30% and ~50% reduction in S. aureus colonization and carriage. In non-smoking men aged 44-60 years, the odds ratio for S. aureus colonization was 0.44 (95% confidence interval, 0.28-0.69) in the top tertile of serum 25(OH)D versus the bottom tertile. In women and smokers there were no such associations. Our study supports that serum vitamin D is a determinant of S. aureus colonization and carriage.

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 17ß-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 17ß-estradiol. Short (<10 years) versus long (>13.5 years) 'menarche-to-first birth' interval was associated with higher overall mean (P(trend) = 0.029), 47% higher maximum peak and 30% higher mid-cycle levels of 17ß-estradiol. We observed a 2.6% decrease in overall mean salivary 17ß-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.

Body fat, energy balance and estradiol levels: a study based on hormonal profiles from complete menstrual cycles.

BACKGROUND: Female fecundity is regulated by nutritional status. Although widely cited, this hypothesis is not strongly supported by empirical data from non-obese, healthy women of reproductive age. METHODS: Healthy, reproductive aged women (n = 141) from Southern Poland collected daily morning saliva samples for one complete menstrual cycle. Levels of 17-beta-estradiol were analyzed by radioimmunoassay. Anthropometric measurements, including body fat percentage, were taken randomly with respect to phase of the menstrual cycle. Energy balance was specified based on changes in body fat percentage from the beginning to the end of the observation period. RESULTS: Women with very low and high body fat had significantly lower levels of E2 compared with women with low and average body fat. In women of very low to average body fat, a 10% increase in body fat was associated with a 5-7 pmol/l increase in estradiol levels. The association between fat percentage and E2 was even stronger in women with positive energy balance, who also showed significant differences between body fat groups in estradiol profiles across whole the menstrual cycle. No such relationship was found in women with negative energy balance. CONCLUSIONS: In healthy women, we found a non-linear association between body fat and estradiol levels. Both very low and high body fat was associated with decreased estradiol levels. The relationship between estradiol and body fat was strongly influenced by women's energy balance.

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.

The effect of exercise on fatigue and physical functioning in breast cancer patients during and after treatment and at 6 months follow-up: A meta-analysis.

Breast cancer is the leading cause of cancer in women worldwide. Exercise interventions may improve physical and psychological factors during and after active breast cancer treatment. The aim of this systematic review was to assess the current knowledge regarding the efficacy of physical exercise with respect to fatigue and self-reported physical functioning. Systematic searches in Cochrane Library, Medline, Embase, Cinahl, PsycINFO, AMED and PEDro. After assessing the quality of the studies, we identified 25 randomized controlled trials that included 3418 breast cancer patients. An increase in physical functioning and a decrease in fatigue were observed after a physical exercise intervention, with an SMD of 0.27 (0.12, 0.41) and -0.32 (-0.49, - 0.14), respectively. There were slightly higher improvements in physical functioning and fatigue when the patients received the intervention after adjuvant breast cancer treatment. The 6-month follow-up data showed a small favourable difference for the physical exercise group for both physical functioning and fatigue. This systematic review found that an exercise intervention program can produce short-term improvements in physical functioning and can reduce fatigue in breast cancer patients. However, more studies are needed to confirm the time-dependent observations in this study.

Physical activity improves the metabolic risk profiles in men and women: the Tromsø Study.

BACKGROUND: Because physical activity may affect risk of certain chronic diseases, we wanted to examine the effects of leisure time physical activity on the metabolic profiles. METHODS: In a population-based cohort study, 5220 men and 5869 women, aged 20 to 49 years at entry, took part in 2 surveys (1979-1980 and 1986-1987) with repeated assessments of self-reported leisure time activity. Measurements of body mass index (measured as the weight in kilograms divided by the square of the height in meters [BMI]) and levels of serum triglyceride, total cholesterol (total C), and high-density lipoprotein cholesterol (HDL-C) were studied in relation to 4 levels of physical activity. RESULTS: There was a dose-response relationship between serum lipid levels and BMI, and levels of physical activity in both sexes after adjustments for potential confounders. Differences in BMI and serum lipid levels between sedentary and sustained exercising groups were consistently more pronounced after 7 years than at baseline, especially in the oldest age group. Men reporting sustained very hard exercising compared with sedentary men had lower total C concentrations (5.65 mmol/L vs 6.21 mmol/L [218 mg/dL vs 240 mg/dL]), triglyceride levels (1.34 mmol/L vs 1.85 mmol/L [118 mg/dL vs 164 mg/dL] ), total C/HDL-C ratios by 19.0%, and BMI (23.9 kg/m2 vs 25.7 kg/m2), and higher HDL-C levels (1.52 mmol/L vs 1.36 mmol/L [59 mg/dL vs 52 mg/dL]). The combined sustained hard and very hard exercising group of women compared with sedentary women had lower total C concentrations (5.70 mmol/L vs 5.90 mmol/L [220 mg/ dL vs 228 mg/dL]), triglyceride levels (1.03 mmol/L vs 1.18 mmol/L [91 mg/dL vs 104 mg/dL]), total C/HDL-C ratios by 7.5%, BMI (23.1 kg/m2 vs 23.6 kg/m2), and higher HDL-C levels (1.73 mmol/L vs 1.66 mmol/L [67 mg/dL vs 64 mg/ dL]). An increase in leisure time activity over the 7 years improved metabolic profiles, whereas a decrease worsened them in both sexes. CONCLUSIONS: Sustained high levels and change from sedentary to higher levels of physical activity relative to sedentary men and women improved the metabolic risk profiles in both sexes. The differences observed are sufficiently large to have a beneficial effect in the prevention of certain chronic diseases.

Increase in weight in all birth cohorts in a general population: The Tromsø Study, 1974-1994.

BACKGROUND: Obesity is a risk factor for a number of chronic diseases. Few longitudinal studies have examined changes in body mass index (BMI [calculated as weight in kilograms divided by the square of the height in meters]). OBJECTIVE: To investigate the changes in mean BMI and the prevalence of obesity in a large cohort examined several times during a 20-year period. METHODS: Mean BMI, the percentage of subjects with low BMI (<20 kg/m(2)), and the percentage who were obese (BMI > or =30 kg/m(2)) were determined in a large population of men and women who were examined up to 4 times during a 20-year period (1974-1994/1995). In a longitudinal design, we observed 3541 men who attended all 4 screenings (1974-1994/1995) and 4993 women who attended the last 3 screenings (1979/1980-1994/1995). RESULTS: The age- (25-49 years) and sex-adjusted mean BMI increased 1 kg/m(2) in men from 1974 to 1994/1995 and 0.9 kg/m(2)in women from 1979/1980 to 1994/1995. In the last survey, subjects aged 25 to 85 years were included. In most age groups, the mean BMI exceeded 25 kg/m(2) and the prevalence of obesity was 10% or higher in men and women aged 45 years or older. In the longitudinal analysis, the mean BMI in men aged 20 to 49 years increased 2.0 kg/m(2) during 20 years of observation and increased 2.4 kg/m(2)in women aged 20 to 49 years during 15 years of observation. The increase in BMI was larger in younger men than in older men. CONCLUSIONS: Body mass index increased in every examined birth cohort (1925-1964) during the 15- to 20-year observation period. Primary prevention of further increased body weight should be a priority.

Assessments of physical activity and cancer risk.

The assessment of physical activity is one of the most important methodological issues in research into physical activity and cancer risk. A sedentary Western lifestyle has been observed to influence biological mechanisms promoting development of certain types of cancer. At present the totality of evidence supports a protective effect against cancers of the colon and probably the breast, while further data concerning carcinoma of other cancers are required. Thus, physical activity represents a powerful public health measure for reducing cancer risk. Studies of the association between physical activity and cancer risk have used a great variety of methods, but have most often included work and/or leisure time activity. Questionnaires are the method most often used and various components of physical activity such as type, frequency, intensity and lifetime physical activity have been recorded. However, the measurements used when assessing physical activity have been hampered by lack of accuracy as regards validity and reliability, missing information on the various components of physical activity and sparse information of lifetime exposure, and often no repeat assessments in cohort studies. Discrepancies between studies elaborating the association between physical activity and site-specific cancer risk may be explained through real differences or lack of information on the various components of physical activity (type, intensity, duration) and incomplete information about the cancer type studied (localization, histological type). The complicated nature of the variable physical activity, combined with incomplete understanding of the pathogenesis of most cancer and lack of knowledge regarding possible biological mechanisms operating between physical activity and cancer, warrants further studies. In these studies methodological improvements in measuring physical activity, combined with inclusion of physiological markers (heart rate, energy balance, hormonal levels, etc.) reflecting the variety of physical activities performed are of particular interest. Assessing biomarkers and intermediate steps for site-specific cancer risk may give us further insight into the relation between physical activity and cancer that will be of enormous interest for public health recommendations.

Energetic factors, ovarian steroids and the risk of breast cancer.

In industrial countries, women often have excess metabolic energy due to high food consumption and low physical activity. High lifetime energy availability results in high lifetime levels of ovarian steroid hormones. Oestrogens and progesterone are hypothesized to play a crucial role in the development and prognosis of breast cancer. Epidemiological studies document the importance of physical activity and caloric limitations in reducing breast cancer risk. The risk of breast cancer is much higher in industrial countries than in developing countries, where women are characterized by lower energy intake and higher energy expenditure. It is likely, that the beneficial effects of physical activity and of negative energy balance are mediated by the reduced levels of ovarian steroids. While both weight loss and physical activity may have similar efficacy in suppressing ovarian function and, therefore, in reducing the risk of breast cancer, we suggest that it may be more advantageous for premenstrual women to achieve lifetime reduction in steroid levels by increasing their physical activity, rather than by weight loss due to caloric restriction alone.

Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

PURPOSE: The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. METHODS: Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. RESULTS: The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect modifiers, e.g., body mass index. Furthermore, data concerning carcinoma of other cancers (prostate, lung, endometrium, ovary, and testicular cancers) are required. CONCLUSION: A protective effect of physical activity on site-specific cancer risk with a dose-response association between physical activity and colon and pre- and postmenopausal breast cancer supported by identified biological mechanisms has been observed. The optimal permutation of type, intensity, duration, and frequency of physical activity across the lifespan is unclear, but it is gender, age, and site specific and supports moderate activity (>4.5 MET) more than light activities (<4.5 MET). The complicated nature of the physical activity variable, combined with lack of knowledge regarding possible biological mechanisms operating between physical activity and cancer, warrants further studies including controlled clinical randomized trials.

Higher luteal progesterone is associated with low levels of premenstrual aggressive behavior and fatigue.

Contradictory findings show both positive and negative effect of progesterone on the premenstrual mood changes in women. Here we present the study investigating this relationship on the large sample of premenstrual women. 122 healthy, reproductive age women collected daily morning saliva samples and recorded intensity scores for the mood symptoms: irritability, anger, sadness, tearfulness, insomnia, and fatigue. Saliva samples were assayed for progesterone concentrations and mood intensity scores were used to calculate behavioral indices. Women with low Aggression/Irritability and Fatigue had consistently higher progesterone levels during the luteal phase than women with high Aggression/Irritability and Fatigue. Additionally, Aggression/Irritability and Fatigue correlated negatively with maximal progesterone value during the luteal phase. Our results demonstrated a negative effect of low progesterone level on the premenstrual mood symptoms such as aggressive behavior and fatigue in healthy reproductive age women. This supports a previously proposed model of biphasic action of progesterone metabolites on mood.