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.Anthropolog

Evidence-based interventions in dementia: A pragmatic cluster-randomised trial of an educational intervention to promote earlier recognition and response to dementia in primary care (EVIDEM-ED)

Background: The National Dementia Strategy seeks to enhance general practitioners' diagnostic and management skills in dementia. Early diagnosis in dementia within primary care is important as this allows those with dementia and their family care networks to engage with support services and plan for the future. There is, however, evidence that dementia remains under-detected and sub-optimally managed in general practice. An earlier unblinded, cluster randomised controlled study tested the effectiveness of educational interventions in improving detection rates and management of dementia in primary care. In this original trial, a computer decision support system and practice-based educational workshops were effective in improving rates of detecting dementia although not in changing clinical management. The challenge therefore is to find methods of changing clinical management. Our aim in this new trial is to test a customised educational intervention developed for general practice, promoting both earlier diagnosis and concordance with management guidelines.Design/Method: The customised educational intervention combines practice-based workshops and electronic support material. Its effectiveness will be tested in an unblinded cluster randomised controlled trial with a pre-post intervention design, with two arms; normal care versus the educational intervention. Twenty primary care practices have been recruited with the aim of gaining 200 patient participants. We will examine whether the intervention is effective, pragmatic and feasible within the primary care setting. Our primary outcome measure is an increase in the proportion of patients with dementia who receive at least two dementia-specific management reviews per year. We will also examine important secondary outcomes such as practice concordance with management guidelines and benefits to patients and carers in terms of quality of life and carer strain.Discussion: The EVIDEM-ED trial builds on the earlier study but the intervention is different in that it is specifically customised to the educational needs of each practice. If this trial is successful it could have implications for the implementation of the National Dementia Strategy

Physical activity and risk of cancer in middle-aged men

A prospective study was carried out to examine the relationship between physical activity and incidence of cancers in 7588 men aged 40–59 years with full data on physical activity and without cancer at screening. Physical activity at screening was classified as none/occasional, light, moderate, moderately-vigorous or vigorous. Cancer incidence data were obtained from death certificates, the national Cancer Registration Scheme and self-reporting on follow-up questionnaires of doctor-diagnosed cancer. Cancer (excluding skin cancers) developed in 969 men during mean follow-up of 18.8 years. After adjustment for age, smoking, body mass index, alcohol intake and social class, the risk of total cancers was significantly reduced only in men reporting moderately-vigorous or vigorous activity; no benefit seen at lesser levels. Sporting activity was essential to achieve significant benefit and was associated with a significant dose-response reduction in risk of prostate cancer and upper digestive and stomach cancer. Sporting (vigorous) activity was associated with a significant increase in bladder cancer. No association was seen with colo-rectal cancer. Non-sporting recreational activity showed no association with cancer. Physical activity in middle-aged men is associated with reduced risk of total cancers, prostate cancer, upper digestive and stomach cancer. Moderately-vigorous or vigorous levels involving sporting activities are required to achieve such benefit.   http://www.bjcancer.com © 2001 Cancer Research Campaig

The use and interpretation of anthropometric measures in cancer epidemiology: A perspective from the world cancer research fund international continuous update project

Anthropometric measures relating to body size, weight and composition are increasingly being associated with cancer risk and progression. Whilst practical in epidemiologic research, where population-level associations with disease are revealed, it is important to be aware that such measures are imperfect markers of the internal physiological processes that are the actual correlates of cancer development. Body mass index (BMI), the most commonly used marker for adiposity, may mask differences between lean and adipose tissue, or fat distribution, which varies across individuals, ethnicities, and stage in the lifespan. Other measures, such as weight gain in adulthood, waist circumference and waist-to-hip ratio, contribute information on adipose tissue distribution and insulin sensitivity. Single anthropometric measures do not capture maturational events, including the presence of critical windows of susceptibility (i.e., age of menarche and menopause), which presents a challenge in epidemiologic work. Integration of experimental research on underlying dynamic genetic, hormonal, and other non-nutritional mechanisms is necessary for a confident conclusion of the overall evidence in cancer development and progression. This article discusses the challenges confronted in evaluating and interpreting the current evidence linking anthropometric factors and cancer risk as a basis for issuing recommendations for cancer prevention

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/m2), waist circumference (WC, cm), waist-to-hip ratio (WHR) and fat percentage dual energy X-ray absorptiometry, (DEXA). Daily salivary 17-b-estradiol (E2) 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 (12 years), the overall mean salivary E2 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 E2 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-b-estradiol throughout the menstrual cycle.AnthropologyHuman Evolutionary Biolog

Introducing willingness-to-pay for noise changes into transport appraisal: an application of benefit transfer.

Numerous research studies have elicited willingness-to-pay values for transport-related noise, however, in many industrialised countries including the UK, noise costs and benefits are still not incorporated into appraisals for most transport projects and policy changes (Odgaard et al, 2005; Grant-Muller et al, 2001). This paper describes the actions recently taken in the UK to address this issue, comprising: primary research based on the city of Birmingham; an international review of willingness-to-pay evidence; development of values using benefit transfers over time and locations; and integration with appraisal methods. Amongst the main findings are: that the willingness-to-pay estimates derived for the UK are broadly comparable with those used in appraisal elsewhere in Europe; that there is a case for a lower threshold at 1 45dB(A)Leq,18hr1 rather than the more conventional 55dB(A); and that values per dB(A) increase with the noise level above this threshold. There are significant issues over the valuation of rail versus road noise, the neglect of non-residential noise and the valuation of high noise levels in different countries. Conclusions are drawn regarding the feasibility of noise valuation based on benefit transfers in the UK and elsewhere, and future research needs in this field are discussed

Risk of testicular germ-cell tumours in relation to childhood physical activity

The US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case–control study of testicular germ-cell tumours (TGCTs) enrolled participants and their mothers in 2002–2005. Hours of sports or vigorous childhood physical activity per week were ascertained for three time periods; 1st–5th grades, 6th–8th grades and 9th–12th grades. Son- and mother-reports were analysed separately and included 539 control son–mother pairs and 499 case son–mother pairs. Odds ratios and 95% confidence intervals were produced. The analysis of the sons' responses found no relationship between childhood physical activity and TGCT, while the mothers' analysis found an inverse association, which was solely due to nonseminoma. Future studies should seek to validate responses further using recorded information sources such as school records

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 17β-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, 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