Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) published evidence-based recommendations for cancer prevention focusing on body weight, physical activity, and diet. Our aim is to evaluate whether adherence to the WCRF/AICR recommendations could reduce endometrial cancer risk. We used data from a multicentric, Italian hospital-based case–control study (1992–2006) including 454 endometrial cancer cases and 908 age-matched controls. Adherence to the WCRF/AICR recommendations was measured using a score (range: 0–7) based on seven components: body mass index (BMI), physical activity and five dietary items; higher scores indicated higher adherence. Odds ratios (OR) were estimated by multiple (adjusted) conditional logistic regression models including terms for major confounders and energy intake. Adherence to the WCRF/AICR recommendations was inversely related to endometrial cancer risk (OR = 0·42, 95 % confidence interval (CI) 0·30, 0·61 for the highest compared with the lowest score quartile), with a significant trend of decreasing risk with increasing adherence. An inverse association was also observed for a score including only dietary recommendations (OR = 0·67, 95 % CI 0·46, 0·96 for the highest compared with the lowest score tertile). In stratified analyses, the association was stronger among women with a normal weight, those who were older, and consequently those in post-menopause, and those with ≥ 2 children. In conclusion, high adherence to the WCRF/AICR recommendations has a favourable role in endometrial cancer risk, which is not fully explained by body weight.

This study aimed to investigate the association between diet and the risk of breast, endometrial and ovarian cancer in the UK Women’s Cohort Study. A total of 35 372 women aged 35–69 years were enrolled between 1995 and 1998 and completed a validated 217-item FFQ. The individual foods were collapsed into sixty-four main food groups and compared using Cox proportional models, adjusting for potential confounders. Hazard ratio (HR) estimates are presented per portion increase in food items. After approximately 18 years of follow-up, there were 1822, 294 and 285 cases of breast, endometrial and ovarian cancer, respectively. A high consumption of processed meat and total meat was associated with an increased risk of breast and endometrial cancer. High intake of tomatoes (HR 0·87, 99 % CI 0·75, 1·00) and dried fruits (HR 0·60, 99 % CI 0·37, 0·97) was associated with a reduced risk of breast and endometrial cancer, respectively. Mushroom intake was associated with a higher risk of ovarian cancer (HR 1·57, 99 % CI 1·09, 2·26). Subgroup analysis by pre- or postmenopausal cancer further demonstrated an association between processed meat intake and both postmenopausal breast cancer and endometrial cancer. Intake of dried fruits was associated with a reduced risk of postmenopausal endometrial cancer (HR 0·55, 99 % CI 0·31, 0·98). Our findings suggest that while some foods may trigger the risk of these cancers, some foods may also be protective; supporting the call for further randomised controlled trials of dietary interventions to reduce the risk of cancer among pre- and postmenopausal women.

Due to increased longevity, women can expect to live more than one-third of their lives in a post-menopausal state, which is characterised by low circulating levels of oestrogen and progesterone. The aim of this review is to provide insights into current knowledge of the effect of female hormones (or lack of female hormones) on skeletal muscle protein turnover at rest and in response to exercise. This review is primarily based on data from human trials. Many elderly post-menopausal women experience physical disabilities and loss of independence related to sarcopenia, which reduces life quality and is associated with substantial financial costs. Resistance training and dietary optimisation can counteract or at least decelerate the degenerative ageing process, but lack of oestrogen in post-menopausal women may reduce their sensitivity to these anabolic stimuli and accelerate muscle loss. Tendons and ligaments are also affected by sex hormones, but the effect seems to differ between endogenous and exogenous female hormones. Furthermore, the effect seems to depend on the age, and as a result influence the biomechanical properties of the ligaments and tendons differentially. Based on the present knowledge oestrogen seems to play a significant role with regard to skeletal muscle protein turnover. Therefore, oestrogen/hormonal replacement therapy may counteract the degenerative changes in skeletal muscle. Nevertheless, there is a need for greater insight into the direct and indirect mechanistic effects of female hormones before any evidence-based recommendations regarding type, dose, duration and timing of hormone replacement therapy can be provided.

Carotenoids are found in abundance in fruit and vegetables, and may be involved in the positive association of these foods with bone health. This study aimed to explore the associations of dietary carotenoid intakes and plasma concentrations with bone density status and osteoporotic fracture risk in a European population. Cross-sectional analyses (n 14 803) of bone density status, using calcaneal broadband ultrasound attenuation (BUA) and longitudinal analyses (n 25 439) of fracture cases were conducted on data from the prospective European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of middle-aged and older men and women. Health and lifestyle questionnaires were completed, and dietary nutrient intakes were derived from 7-d food diaries. Multiple regression demonstrated significant positive trends in BUA for women across quintiles of dietary α-carotene intake (P=0·029), β-carotene intake (P=0·003), β-cryptoxanthin intake (P=0·031), combined lutein and zeaxanthin intake (P=0·010) and lycopene intake (P=0·005). No significant trends across plasma carotenoid concentration quintiles were apparent (n 4570). The Prentice-weighted Cox regression showed no trends in fracture risk across dietary carotenoid intake quintiles (mean follow-up time 12·5 years), except for a lower risk for wrist fracture in women with higher lutein and zeaxanthin intake (P=0·022); nevertheless, inter-quintile differences in fracture risk were found for both sexes. Analysis of plasma carotenoid data (mean follow-up time 11·9 years) showed lower hip fracture risk in men across higher plasma α-carotene (P=0·026) and β-carotene (P=0·027) quintiles. This study provides novel evidence that dietary carotenoid intake is relevant to bone health in men and women, demonstrating that associations with bone density status and fracture risk exist for dietary intake of specific carotenoids and their plasma concentrations.

The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.

The relation between inflammation deriving from diet and endometrial cancer risk has not yet been investigated. In this study, we explored the association between the dietary inflammatory index (DII) and endometrial cancer risk in an Italian case–control study. Cases comprised 454 patients with incident, histologically confirmed carcinoma of the endometrium, and controls comprised 908 subjects admitted to the same network of hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. DII scores were computed on the basis of dietary intake assessed using a reproducible and valid seventy-eight-item FFQ. OR were calculated through logistic regression models conditioned on age and study centre and adjusted for recognised confounding factors, including total energy intake. Women with the most pro-inflammatory diet had a higher risk for endometrial cancer compared with women with the most anti-inflammatory diet (ORQuartile 4 v. 1 1·46; 95 % CI 1·02, 2·11; Ptrend=0·04). A pro-inflammatory diet may increase the risk for endometrial cancer.

Objective: To study the implications of hormone replacement therapy (HRT) treatment in the pathogenesis of Reinke's oedema (via a possible pseudo-hypothyroidism effect), and also to study why the disease affects a predominantly post-menopausal female population.

Design: Prospective case series study.

Setting: Two teaching hospitals and two district general hospitals in Scotland, UK.

Subjects: Thirty-three patients diagnosed with Reinke's oedema who presented in the out-patient department before or after treatment.

Results: Thyroid function tests were normal in all but two cases. Only three patients were receiving HRT treatment.

Conclusions: The study produced no evidence to support a relationship between HRT treatment and the pathogenesis of Reinke's oedema; this supports previous studies which concluded that thyroid function was not related to the development of Reinke's oedema. Some new ideas regarding hormonal factors in Reinke's oedema are discussed.

Objectives: The purpose of the study is to reassess the cost-effectiveness of hormone replacement therapy (HRT) based on new medical evidence found in the Women's Health Initiative (WHI). Within a model framework using an individual state transition model, the cost-effectiveness of 50- to 60-year-old women with menopausal symptoms is assessed based on a societal perspective in Sweden.

Methods: The model has a 50-year time horizon divided into a cycle length of 1 year. The model consists of the following disease states: coronary heart disease, stroke, venous thromboembolic events, breast cancer, colorectal cancer, hip fracture, vertebral fracture, and wrist fracture. An intervention is modeled by its impact on the disease risks during and after the cessation of therapy. The model calculates costs and quality-adjusted life years (QALYs) with and without intervention. The resulting cost per QALY gained is compared with the value of a QALY gained, which is set to SEK 600,000. The model requires data on clinical effects, risks, mortality rates, quality of life weights, and costs valid for Sweden.

Results: The cost-effectiveness ratios are estimated at approximately SEK 10,000, which is below the threshold value of cost-effectiveness. On the condition that HRT increases the quality of life weight more than 0.013 units, the therapy is cost-effective.

Conclusions: In conclusion, given the new evidence in WHI, there is still a high probability that HRT is a cost-effective strategy for women with menopausal symptoms.