Search

Objective: This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women., Methods: The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography-tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders., Results: The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7-77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) ( p  = 0.002 and p  < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol ( p  = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) ( p  = 0.024, p  = 0.003 and p  < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C ( p  = 0.024)., Conclusions: In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

Cardiovascular disease (CVD) is the leading cause of death in women aged 65 years and older. Sex hormones have been implicated as having a critical role in the evolution of CVD, with the focus mainly on estrogens in women. Available data also indicate that low testosterone blood levels may be detrimental to cardiovascular function in women. At blood concentrations considered normal for premenopausal women, testosterone has favorable effects on blood vessel function (relaxation and contraction), much of which is determined by the endothelial cells that line the inside of blood vessels. Testosterone enhances endothelium-dependent and independent brachial artery vasodilation and has an acute systolic blood pressure-lowering effect in postmenopausal women. Advantageous effects of testosterone in animal models have been seen for myocardial function and cardiac electrical signaling. Human data are mainly limited to observational and mechanistic studies, which mostly demonstrate beneficial effects of testosterone on cardiovascular health. Few studies of testosterone use in women, with cardiovascular endpoints as primary outcomes, have been published.

Objective: The Practitioner's Toolkit for Managing the Menopause, developed in 2014, provided an accessible desk-top tool for health-care practitioners caring for women at midlife. To ensure the Toolkit algorithms and supporting information reflect current best practice, the Toolkit has been revised in accordance with the published literature., Methods: A systematic search for guidelines, position and consensus statements pertaining to the menopause and published after 2014 was undertaken, and key recommendations extracted from the Clinical Practice Guidelines determined to be the most robust by formal evaluation. The peer-reviewed literature was further searched for identified information gaps., Results: The revised Toolkit provides algorithms that guide the clinical assessment and care of women relevant to menopause. Included are the reasons why women present, information that should be ascertained, issues that may influence shared decision-making and algorithms that assist with determination of menopausal status, menopause hormone therapy (MHT) and non-hormonal treatment options for symptom relief. As clear guidelines regarding when MHT might be indicated to prevent bone loss and subsequent osteoporosis in asymptomatic women were found to be lacking, the Toolkit has been expanded to support shared decision-making regarding bone health., Conclusions: The 2023 Toolkit and supporting document provide accessible desk-top information to support health-care providers caring for women at midlife.The Toolkit has been endorsed by the International Menopause Society, Australasian Menopause Society, British Menopause Society, Endocrine Society of Australia and Jean hailes for Women's Health.

Refugee and asylum seeker women face a variety of health challenges. However, little is known globally about health problems in these women at midlife and beyond, including menopausal symptoms, sexual dysfunctions and pelvic floor disorders. This scoping review aimed to understand these neglected health issues with respect to prevalence and risk factors. Eight databases were searched in August 2022 without the limit of publication year. Data were analyzed narratively. A total of 10 reports from seven studies were included with 945 women living in Australia, Canada, the USA and Pakistan. Three reports were addressing menopause, seven addressed sexual dysfunctions and one addressed pelvic floor disorders. There were no data regarding menopause symptoms; however, perceptions of menopause varied widely across studies. Few studies reported a high prevalence of sexual dysfunctions and pelvic organ prolapses, but none of them used a validated questionnaire. Taboos and cultural factors, lack of knowledge and education, lack of family support, language insufficiency and financial problems were common barriers to not seeking care for these health issues. This review demonstrates lack of evidence of these neglected health issues in refugee and asylum seeker women at midlife, and further studies with validated questionnaires and larger samples are warranted.

Objective: This study aims to explore the associations between sex hormones and cognitive performance in older women., Methods: Associations between sex hormones, sex hormone binding globulin (SHBG) and cognitive performance were examined in women aged at least 70 years, without dementia and not using medications that influence sex hormones. Linear and generalized linear regression models included age, body mass index, education, smoking, alcohol, living circumstances, diabetes, hypertension, depression and impaired renal function., Results: The included 5511 women had a median (interquartile range) age of 73.9 (71.6-77.6) years. No associations were found for estrone, estradiol, testosterone or dehydroepiandrosterone and cognitive performance. SHBG concentrations above quartile 1 (Q1) were significantly inversely associated with processing speed (Q2, β = -0.94, 95% confidence interval [CI] - 1.64 to -0.24, p  = 0.009; Q3, β = -0.82, 95% CI -1.53 to -0.10, p  = 0.025; and Q4, β = -0.95, 95% CI -1.70 to -0.20, p  = 0.013)., Conclusions: Sex hormones were not associated with cognitive performance. The finding that low SHBG is associated with better processing speed warrants further investigation. The null findings for the sex hormones establish a firm baseline to confidently explore the association between sex hormones and longitudinal cognitive performance in this population., Trial Registration: International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and ClinicalTrials.gov (NCT01038583).

Objective: We investigated whether estrone and sex hormone binding globulin (SHBG) concentrations are associated with lipid concentrations in older postmenopausal women., Methods: This was a cross-sectional study of 6358 Australian women, aged 70-95 years, recruited between 2010 and 2014. Associations between estrone and SHBG and lipid concentrations were examined in participants not using medications that influence estrogen concentrations or lipid-lowering therapy. Linear regression models included age, body mass index, smoking, alcohol consumption, renal function and diabetes, with the lowest quartile (Q1) as the reference for estrone and SHBG., Results: The study included 3231 participants with median age of 74.0 (interquartile range 71.7-77.9) years. Estrone concentration Q3 and Q4 were positively associated with high-density lipoprotein cholesterol (HDL-C) ( p  = 0.017 and p  = 0.046, respectively). Inverse associations were seen for estrone Q4 with total cholesterol ( p  = 0.018), Q2 and Q4 with non-HDL-C ( p  = 0.045 and p  = 0.002, respectively) and Q3 and Q4 with triglycerides ( p  = 0.030 and p  = 0.001, respectively). For SHBG, Q2, Q3 and Q4 were positively associated with HDL-C (all p  < 0.001), and inversely with non-HDL-C (all p  = 0.001) and triglycerides (all p  < 0.001)., Conclusions: Estrone and SHBG are associated with lipid concentrations in older women. SHBG, but not estrone, may provide additional clinical predictive utility for the assessment of cardiometabolic disease risk in older women.

The clinical effects of testosterone in women have expanded from the field of androgen excess to consideration of testosterone action and the consequences of depletion and replacement. This article is not a comprehensive review of the vast and increasing literature in this field. Rather, it summarizes some of what is known of testosterone in women that the author elected to highlight in a plenary lecture and is hopefully informative, but not to be considered conclusive.

This review was conducted to explore the association between endogenous testosterone blood concentrations and cognitive performance among community dwelling postmenopausal women. We searched Ovid MEDLINE, EMBASE, PsycINFO and Web of Science databases for observational studies with at least 100 postmenopausal participants. The results were categorized by study design, reporting of total or free testosterone and risk of bias assessments, narratively. Ten of the 26 articles retrieved for full-text review met the inclusion criteria, six provided cross-sectional data, seven provided longitudinal data and one provided case-control data. Cognitive performance tests differed between studies. Eight studies measured testosterone by immunoassay, one by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and one did not specify their methodology. Eleven different cognitive domains were tested by 37 different instruments. Irrespective of the study design, the findings were inconsistent and inconclusive. Both positive and inverse associations were reported for each of global cognition and immediate and delayed verbal recall. The majority of studies reported no association between total or free testosterone and cognitive performance. Although this review did not demonstrate an association between testosterone and cognitive performance in postmenopausal women, the findings should be considered inconclusive due to the imprecision of testosterone measurement and the methodological heterogeneity of the included studies.

Accurate and timely pregnancy diagnosis is an important component of effective herd management in dairy cattle. Predicting pregnancy from Fourier-transform mid-infrared (FT-MIR) spectroscopy data is of particular interest because the data are often already available from routine milk testing. The purpose of this study was to evaluate how well pregnancy status could be predicted in a large data set of 1,161,436 FT-MIR milk spectra records from 863,982 mixed-breed pasture-based New Zealand dairy cattle managed within seasonal calving systems. Three strategies were assessed for defining the nonpregnant cows when partitioning the records according to pregnancy status in the training population. Two of these used records for cows with a subsequent calving only, whereas the third also included records for cows without a subsequent calving. For each partitioning strategy, partial least squares discriminant analysis models were developed, whereby spectra from all the cows in 80% of herds were used to train the models, and predictions on cows in the remaining herds were used for validation. A separate data set was also used as a secondary validation, whereby pregnancy diagnosis had been assigned according to the presence of pregnancy-associated glycoproteins (PAG) in the milk samples. We examined different ways of accounting for stage of lactation in the prediction models, either by including it as an effect in the prediction model, or by pre-adjusting spectra before fitting the model. For a subset of strategies, we also assessed prediction accuracies from deep learning approaches, utilizing either the raw spectra or images of spectra. Across all strategies, prediction accuracies were highest for models using the unadjusted spectra as model predictors. Strategies for cows with a subsequent calving performed well in herd-independent validation with sensitivities above 0.79, specificities above 0.91 and area under the receiver operating characteristic curve (AUC) values over 0.91. However, for these strategies, the specificity to predict nonpregnant cows in the external PAG data set was poor (0.002-0.04). The best performing models were those that included records for cows without a subsequent calving, and used unadjusted spectra and days in milk as predictors, with consistent results observed across the training, herd-independent validation and PAG data sets. For the partial least squares discriminant analysis model, sensitivity was 0.71, specificity was 0.54 and AUC values were 0.68 in the PAG data set; and for an image-based deep learning model, the sensitivity was 0.74, specificity was 0.52 and the AUC value was 0.69. Our results demonstrate that in pasture-based seasonal calving herds, confounding between pregnancy status and spectral changes associated with stage of lactation can inflate prediction accuracies. When the effect of this confounding was reduced, prediction accuracies were not sufficiently high enough to use as a sole indicator of pregnancy status., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Aims: To describe the concentration of Zn in bulk tank milk (BTM) in a sample of New Zealand dairy farms, investigate the association between the method of Zn administration for facial eczema prophylaxis and Zn concentrations in BTM and investigate the relationship between the concentration of Zn in serum and that in BTM., Methods: Multiple BTM samples (n = 3,330) collected during milk pick-up by the milk tanker driver were stored and tested for 121 farms, in Northland (n = 50), Waikato (n = 51) and Southland (n = 20) from February to May 2017. Enrolled farms provided retrospective information on the type of Zn supplementation (if any) used for the prevention of facial eczema and the timeframe over which supplementation occurred. In addition, the concentration of Zn in serum was measured in blood samples collected from ≥15 cattle per farm for 22 farms from Northland (n = 11) and Waikato (n = 11), and compared against the concentrations of Zn in BTM on the day of blood sampling. A linear mixed model was used to model log Zn concentrations in BTM using method of Zn supplementation, region, milk fat and protein percentage, volume of milk, and frequency of milk pick-up as risk factors. A mixed logistic regression model was used to assess the relationship between Zn concentrations in BTM and the presence of cows with a concentration of Zn in serum of ≥20 µmol/L., Results: The median Zn concentration in BTM was 67.9 (min 38.9, max 146.6) µmol/L. The median range of Zn concentrations for repeated samples of BTM within farm was 22.6 µmol/L. In comparison to farms that did not use any form of Zn supplementation, farms that supplemented Zn through a slow-release capsule, oral drench, in feed or a combination of in-feed and water were associated with increased concentrations of Zn in BTM (p < 0.001). There was no difference in Zn concentrations in BTM between farms that administered Zn through the water only and farms that did not administer Zn (p = 0.22). Every 15.3 μmol/L increase in Zn concentration in BTM was associated with 2.2 times (95% CI=1.7-2.9) the odds of a cow having Zn concentration in serum ≥20 μmol/L., Conclusion and Clinical Relevance: Zn concentration in BTM is highly variable between farms, days and Zn administration method. Zn concentration in BTM content has modest potential as a way to signal whether a herd has achieved the high Zn status considered to be protective against FE.

Aims: To investigate the relationship between Zn concentrations in serum and those in milk or faeces, and to assess the ability of the Zn concentrations in milk, serum and faeces to predict intake of ZnO in dairy cattle., Method: Seventy cows from one commercial farm in the Waikato region of New Zealand received one of seven dose rates (0, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 g/100 kg bodyweight (BW)) of ZnO given by oral drench, every morning, for 7 consecutive days. Every afternoon, milk and blood samples were collected from all cows. Free-catch faecal samples were collected during the afternoon milking on 3 days throughout the trial.Linear mixed models were used to assess the relationship between the concentration of Zn in serum and that in milk, and in faeces, respectively, and the relationship between dose rate of ZnO and concentrations of Zn in serum, faeces and milk, respectively. Receiver operating characteristic curve analysis was used to determine the ability of the Zn concentration in serum, milk and faeces to predict that a cow had been treated with a dose of ZnO ≥2.5 g/100 kg, the industry-recommended dose rate needed to protect against facial eczema., Results: A 1-µmol/L increase in Zn concentration in milk was associated with a 0.14 (95% CI = 0.11-0.17) µmol/L increase in Zn concentration in serum. Zn concentration in faeces was scaled by its SD; a 1 SD increase was associated with a 1.83 (95% CI = 0.54-3.12) µmol/L increase in zinc concentration in serum. Zn concentrations in serum and faeces increased with increasing dose rates of ZnO. No differences in Zn concentrations in milk were noted between animals dosed with 1.5-3.5 g ZnO/100 kg BW, inclusive. At the optimal threshold of Zn concentration in serum to predict protective ZnO intake (22 µmol/L), the sensitivity was 0.76 (95% CI = 0.69-0.82) and specificity 0.85 (95% CI = 0.80-0.89). For the concentration of Zn in faeces, the optimal threshold was 17.36 mmol/kg, with a corresponding sensitivity of 0.84 (95% CI = 0.84-0.85) and specificity of 0.85 (95% CI = 0.73-0.94). At the optimal threshold for the Zn concentration in milk (76.6 µmol/L), the sensitivity was lower than the other two sample types at 0.59 (95% CI = 0.52-0.67), but with a similar specificity of 0.84 (95% CI = 0.79-0.88)., Conclusions and Clinical Relevance: The concentration of Zn in milk shows promise as an initial screening test to identify dairy farms that do not provide adequate zinc to provide protection against FE.

Objective: This study aimed to explore Australian health-care providers' knowledge of menopause and its consequences, and their views about menopause-related health care., Methods: This was a cross-sectional qualitative study of Australian general practitioners (GPs), gynecologists (GYs) and pharmacists (PHs). Recruitment was ultimately achieved through professional networks and cold calling., Results: There were equal numbers of GPs, GYs and PHs, and equal numbers of males and females in each group. All participants demonstrated sound understanding of menopause and its consequences. A strong theme was recognition of high usage of complementary and alternative medicines (CAMs) by women for menopausal symptoms. Most participants highlighted lack of efficacy evidence for most CAMs, but the majority of GPs and PHs considered CAMs to 'have a role'. Most supported menopausal hormone therapy (MHT) when symptoms impaired quality of life. Limitations to comprehensive care included knowledge gaps and lack of time., Conclusions: Australian health-care providers appeared knowledgeable about menopause, but uncertain about its management. MHT prescription appeared limited to women with severe symptoms despite lifestyle modification and a trial of CAMs. The upskilling of clinicians providing care for women at midlife, with respect to the indications for and prescribing of MHT, urgently needs to be addressed.

Premature ovarian insufficiency (POI) results in both estrogen and testosterone insufficiency. Whether testosterone therapy may be of benefit for women with POI is uncertain. Presently, the only evidence-based indication for testosterone therapy for women is for the treatment of postmenopausal women with low sexual desire with associated personal distress. Consistent with this, available evidence does not support the prescription of testosterone to prevent cardiometabolic disease, bone loss, sarcopenia, or cognitive decline or to improve well-being and low mood in postmenopausal women. Data pertaining to the treatment of women with POI with testosterone are limited. This article reviews androgen physiology in premenopausal women and the impact of POI on circulating androgen concentrations, summarizes findings from observational studies and clinical trials of testosterone therapy in premenopausal women and women with POI, and concludes with recommendations regarding testosterone use in women with POI.

The physiological, clinical and therapeutic aspects of testosterone in women's health are still a matter of controversy and debate. Quality evidence data of clinical trials favors the use of transdermal testosterone in postmenopausal women with female sexual dysfunction causing distress. Doses of testosterone should approximate physiological testosterone levels found in premenopausal women, avoiding supraphysiological concentrations that expose women to adverse events. Short-term treatment periods have been shown to be effective and safe in postmenopausal women with hypoactive sexual desire disorder/dysfunction. However, long-term safety of testosterone use must be determined.

Background: This study was undertaken to determine women's knowledge of menopause and its consequences, and their menopause-related health-care experiences., Methods: Participants were recruited to this cross-sectional qualitative study from a nationally, representative sample of Australian women. Recruitment was stratified by age to achieve groups of premenopausal (PRE), perimenopausal (PERI), early postmenopausal (E-POST), and late postmenopausal (L-POST) women., Results: The 32 participants were aged 46-69 years: 10 PRE, three PERI, 11 E-POST and eight L-POST women. All understood that menopause meant the end of reproductive function and were aware of menopause-associated symptoms. Most PRE and E-POST women referred to lifestyle changes to optimize health, and self-help and complementary therapies to manage symptoms. E-POST and L-POST women were more likely to nominate seeing a doctor for overall health and symptom management. Menopausal hormone therapy (MHT) was viewed negatively, with shared perceptions of cancer risk and over-prescription. A strong theme was lack of knowledge of long-term menopause sequelae, with only four women nominating osteoporosis., Conclusions: Our in-depth qualitative study would suggest that, while Australian midlife women have a good understanding of the immediate effects of menopause, their lack of knowledge of the long-term consequences is concerning. Despite the effectiveness and safety of MHT, the overall attitude to MHT remains negative.

The objective of this study was to estimate genetic correlations among milk fatty acid (FA) concentrations in New Zealand dairy cattle. Concentrations of each of the most common FA, expressed as a percentage of the total FA, were determined by gas chromatography on a specific cohort of animals. Using this data set, prediction equations were derived using mid-infrared (MIR) spectroscopy data collected from the same samples. These prediction equations were applied to a large data set of MIR measurements in 34,141 milk samples from 3,445 Holstein-Friesian, 2,935 Jersey, and 3,609 crossbred Holstein-Friesian × Jersey cows, sampled an average of 3.42 times during the 2007-2008 season. Data were analyzed using univariate and bivariate repeatability animal models. Heritability of predicted FA concentration in milk fat ranged from 0.21 to 0.42, indicating that genetic selection could be used to change the FA composition of milk. The de novo synthesized FA (C6:0, C8:0, C10:0, C12:0, and C14:0) showed strong positive genetic correlations with each other, ranging from 0.24 to 0.99. Saturated FA were negatively correlated with unsaturated (-0.93) and polyunsaturated (-0.84) FA. The saturated FA were positively correlated with milk fat yield and fat percentage, whereas the unsaturated FA were negatively associated with fat yield and fat percentage. Our results indicate that bovine milk FA composition can be changed through genetic selection using MIR as a phenotypic proxy., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The use of Fourier-transform mid-infrared (FTIR) spectroscopy is of interest to the dairy industry worldwide for predicting milk composition and other novel traits that are difficult or expensive to measure directly. Although there are many valuable applications for FTIR spectra, noise from differences in spectral responses between instruments is problematic because it reduces prediction accuracy if ignored. The purpose of this study was to develop strategies to reduce the impact of noise and to compare methods for standardizing FTIR spectra in order to reduce between-instrument variability in multiple-instrument networks. Noise levels in bands of the infrared spectrum caused by the water content of milk were characterized, and a method for identifying and removing outliers was developed. Two standardization methods were assessed and compared: piecewise direct standardization (PDS), which related spectra on a primary instrument to spectra on 5 other (secondary) instruments using identical milk-based reference samples (n = 918) analyzed across the 6 instruments; and retroactive percentile standardization (RPS), whereby percentiles of observed spectra from routine milk test samples (n = 2,044,094) were used to map and exploit primary- and secondary-instrument relationships. Different applications of each method were studied to determine the optimal way to implement each method across time. Industry-standard predictions of milk components from 2,044,094 spectra records were regressed against predictions from spectra before and after standardization using PDS or RPS. The PDS approach resulted in an overall decrease in root mean square error between industry-standard predictions and predictions from spectra from 0.190 to 0.071 g/100 mL for fat, from 0.129 to 0.055 g/100 mL for protein, and from 0.143 to 0.088 g/100 mL for lactose. Reductions in prediction error for RPS were similar but less consistent than those for PDS across time, but similar reductions were achieved when PDS coefficients were updated monthly and separate primary instruments were assigned for the North and South Islands of New Zealand. We demonstrated that the PDS approach is the most consistent method to reduce prediction errors across time. We also showed that the RPS approach is sensitive to shifts in milk composition but can be used to reduce prediction errors, provided that secondary-instrument spectra are standardized to a primary instrument with samples of broadly equivalent milk composition. Appropriate implementation of either of these approaches will improve the quality of predictions based on FTIR spectra for various downstream applications., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

In cattle, the X chromosome accounts for approximately 3 and 6% of the genome in bulls and cows, respectively. In spite of the large size of this chromosome, very few studies report analysis of the X chromosome in genome-wide association studies and genomic selection. This lack of genetic interrogation is likely due to the complexities of undertaking these studies given the hemizygous state of some, but not all, of the X chromosome in males. The first step in facilitating analysis of this gene-rich chromosome is to accurately identify coordinates for the pseudoautosomal boundary (PAB) to split the chromosome into a region that may be treated as autosomal sequence (pseudoautosomal region) and a region that requires more complex statistical models. With the recent release of ARS-UCD1.2, a more complete and accurate assembly of the cattle genome than was previously available, it is timely to fine map the PAB for the first time. Here we report the use of SNP chip genotypes, short-read sequences, and long-read sequences to fine map the PAB (X chromosome:133,300,518) and simultaneously determine the neighboring regions of reduced homology and true pseudoautosomal region. These results greatly facilitate the inclusion of the X chromosome in genome-wide association studies, genomic selection, and other genetic analysis undertaken on this reference genome., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: This study was undertaken to determine the impact of menopause on middle-eastern women., Methods: This was a cross-sectional study of 1520 women, aged 40-64 years, living in Sari, Northern Iran, recruited by multistage cluster sampling between October 2016 and April 2017. All women completed the Menopause Quality of Life Questionnaire (MENQOL) and Beck Depression Inventory-II (BDI-II)., Results: Of all the women, 54.5% were perimenopausal or postmenopausal. The prevalences of any vasomotor symptom (VMS) and moderate-severely bothersome VMS were greatest for postmenopausal women aged <55 years (66.4%, 95% confidence interval (CI) 59.9-72.3% and 13.5%, 95% CI 9.6-18.6%, respectively). Having moderate-severe VMS was associated with moderate-severe depressive symptoms (adjusted odds ratio (AOR) 2.9; 95% CI 1.6-5.2; p < 0.001). Symptoms of vulvovaginal atrophy (VVA) were reported by 41.1% (95% CI 37.4-45.0%) of perimenopausal and postmenopausal women, with 22.9% (95% CI 19.8-26.3%) reporting their symptoms as moderate-severely bothersome. In women with moderate-severe VMS, the proportion with both moderate-severe depressive symptoms and moderate-severe VVA symptoms (12.1%) was four times that in women with no or mild VMS (3.3%) (p < 0.001)., Conclusion: One in seven perimenopausal and postmenopausal women has moderate-severely bothersome VMS and few women receive appropriate therapy. The reporting of moderate-severe VMS should alert clinicians to the likelihood of significant concurrent VVA and depressive symptoms.

Sexual well-being frequently declines following the menopause transition and can be associated with significant personal and relationship distress. This distress is the hallmark of female sexual dysfunction (FSD). FSD is highly prevalent in postmenopausal women. The prevalence of sexual problems increases with age, but conversely this is associated with decreasing distress with advancing age. This pattern has been seen across multiple international populations with varied cultural norms. While the etiology of FSD is multifactorial, the physiological changes of sex hormone insufficiency and postmenopausal symptoms, such as dyspareunia, are primary factors contributing to FSD at midlife. The International Menopause Society is working to increase awareness of FSD and to provide a framework for practitioners to address sexual medicine concerns. This White Paper aims to review the process of care for female sexual well-being following menopause, from initially approaching the discussion of FSD, to identifying clinical signs and symptoms, and ultimately determining the best available biopsychosocial therapies. As with most processes of care, the first step is often the most difficult. Health-care practitioners need to broach the topic of sexuality in the clinical setting. Lack of information on, comfort with, and biases about the topic of sexuality after menopause are significant hurdles that the International Menopause Society addresses in this document. Each member of the Writing Group remains committed to continued advocacy for the validity of FSD as a diagnosis, the need for therapies for women to be both available and included in health insurance coverage, and continued therapeutic research to provide evidence-based solutions.

Objective : Young people with asthma often lack engagement in self-management. Smartphone apps offer an attractive, immediate method for obtaining asthma information and self-management support. In this research we developed an evidence-based asthma app tailored to young peoples needs, created using a participatory design approach to optimize user engagement. This paper describes the participatory design process. Methods : This multi-phased research included concept generation and ideation of app design by young people with asthma, and development of asthma information by the research team. Clinical review was sought regarding safety and accuracy of app content. Participants suggestions for improvement and any problems with the app were logged throughout. Our young co-designers were invited back to test a high fidelity prototype app using a "think aloud" process and completed a usability questionnaire. Results : Twenty asthma patients aged 15-24 years contributed to the initial app design. Three respiratory specialists and two pharmacists suggested minor corrections to clinical terminology in the app which were all incorporated. Nine co-designers acted as expert reviewers of the prototype app, of whom eight completed a usability questionnaire. Median usability scores (maximum score 6) indicated high satisfaction with app content, usefulness and ease of use [median item score 5.3 (range 4.7-6.0)]. All feedback was incorporated to create an updated prototype app. Conclusions : A clinically sound asthma app has been developed which is considered highly acceptable to the young co-designers. A six-week test of the engagement, acceptability, and usefulness of the app in young people not involved in the participatory design will follow.

The genetic merit of a herd is a key determinant in productivity for dairy farmers. However, making breeding decisions to maximize the rate of genetic gain can be complex because there is no certainty about which cows will become pregnant with a heifer calf. In this study, breeding worth (BrW) was used as a measure of genetic merit, and several mating strategies were evaluated. These strategies included randomly mating whole herds to the entire bull team, excluding low-ranked cows from producing replacement heifers, and nominating high-ranked cows to the most highly ranked bulls. Simulations were undertaken using 4 bull teams generated from bulls currently marketed in New Zealand and a selection of New Zealand dairy herds. Average replacement heifer BrW was calculated for 1,000 iterations of each combination of mating strategy, herd, and bull team (scenario). Variation in resulting average replacement heifer BrW within scenarios was due to random sampling of which cows became pregnant with a heifer calf. Relative to mating the whole herd to an entire bull team, excluding the lowest ranked cows from producing replacements resulted in the greatest increase in average replacement heifer BrW across all herds and bull teams, with a gain of approximately 0.4 BrW point for each 1% of cows excluded. Nominating top-ranking cows to the highest ranking bulls in the team had little effect (0.06-0.13 BrW increase for each 1% of top cows nominated) in improving BrW of replacement heifers. The number of top bulls nominated had a variable effect depending on the BrW spread of the entire bull team. Although excluding cows with the lowest BrW from producing replacement heifers is most effective for improving BrW, it is important to ensure that the number of heifers born is sufficient to replace cows leaving the herd. It is likely that optimal strategies for improving BrW will vary from farm to farm depending not only on the BrW structure of the herd, the bull team available, and the reproduction success on farm but also on farm management practices. This simulation study provides expected outcomes from a variety of mating strategies to allow informed decision making on farm., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

Background: The menopausal transition may have significant consequences for respiratory health, risk of chronic respiratory disease and management strategies., Objective: To systematically summarize the literature regarding the impact of menopause status on respiratory health outcomes., Methods: PubMed was searched systematically to identify population-based studies investigating the associations between menopause status and respiratory outcomes including asthma, chronic obstructive pulmonary disease (COPD), respiratory symptoms and lung function., Results: Ten publications were identified for full review. Evidence on menopause and asthma was conflicting, while studies on COPD were scarce. The findings generally support an association between menopause and clinically significant reductions in lung function in a non-obstructive pattern. However, the effects of menopause are clouded by aging, menopausal hormone therapy use, and increased risk of metabolic syndrome during this period., Conclusions: As the global burden associated with respiratory conditions continues to rise, the need to understand the associations between menopause and respiratory health is essential to identify potentially modifiable risk factors for respiratory disease in adult women. More studies are needed to clarify the impact of menopause on obstructive lung disease.

Introduction: Women may experience different menopausal symptoms across different cultures around the world. The purpose of this study was to determine the prevalence and contributing factors of depression in midlife women in the Middle East., Methods: Electronic databases including PubMed, Medline, PsycINFO, CINAHL, Web of Science, SCOPUS, and Google scholar were searched. The quality of articles was assessed by using the risk of bias tool., Results: Sixteen articles were used for this review. The prevalence for depressive symptoms in perimenopausal women is higher than in premenopausal women. The overall data also suggest that depressive symptoms may be more prevalent in postmenopausal women than in premenopausal women. Studies reported sociodemographic, physical, psychological, cultural and sexual risk factors for depressive symptoms in middle-aged women. Risk of bias for a majority of the studies conducted in the Middle Eastern region on depression in midlife was moderate., Conclusion: Consistent with other areas in the world, midlife women in the Middle East region are at higher risk for depression due to the presence of different factors. High-quality longitudinal studies of representative samples, using validated questionnaires, are needed to provide more accurate prevalence data and the association between menopause and menopausal symptoms in women in the Middle East.

The number of secretory cells in the mammary gland is often cited as a major determinant of milk production. However, literature data for proxy measures of secretory cell number do not fully support such a claim. In particular, measurements of total mammary DNA in livestock explain only <25% of variation in milk yield, probably because of tissue heterogeneity for DNA concentration. Relative to BW, measurements of udder size in dairy cattle, as total DNA or udder weight, are approximately double those seen in most other livestock classes. Therefore, selection for dairy production, not surprisingly, has resulted in cows with greater secretory capacity. There is limited evidence that genetic selection is still increasing udder size in some cattle populations, but more recent data are needed. It is contended that the most important period of mammary growth for determination of milk yield is that occurring in pregnancy and early lactation. Mammary development is largely complete, at term, in sheep, goats, and cattle, but in pigs, the udder continues to grow during the first 3 wk of lactation, depending, in part, on litter size. Increased litter size in sheep and goats will enhance the extent of mammary development at the end of gestation (and milk yield) by 20 to 25%. However, twinning in dairy cattle does not affect milk production and, by inference only, is not likely to affect numbers of secretory cells at term. Milking frequency and suckling intensity in very early lactation will increase milk yield in cows and increase mammogenesis and milk yield in sheep, indicating that even at term, the ruminant gland retains some capacity for further development, if demand requires it. There is limited understanding of the hormonal signals in pregnancy that regulate mammary development relative to the number of young carried. Furthermore, the genetic differences between dairy and beef cattle that lead to substantially greater udder size in the dairy breeds have not been identified. During lactation, the drivers for secretory cell loss in relation to milking frequency and nutritional status are still not known. Measurement of mammary development and using this phenotype in genomewide association studies to identify key genetic variants for mammogenesis will provide knowledge that is fundamental to understanding the quantitative regulation of milk production.

The aim of this study was to investigate heterogeneity in tissue morphology, milk protein and immune-related gene expression, and apoptosis of epithelial cells in the lactating and involuting mammary glands of the dairy cow. Mammary tissue from different regions of the gland (alveolar, cisternal, and peripheral) was collected postmortem from nonpregnant, pasture-fed, Holstein-Friesian primiparous cows in mid-lactation that were killed at different time points postmilking: 0, 6, 12, 18, 24, 36, and 72 h (n = 6 per time point). The CSN1NS1 and LALBA mRNA was decreased in alveolar, cisternal, and peripheral tissue by 12 to 36 h postmilking. In contrast, lactoferrin (LF) and mammary serum amyloid A3 (M-SAA3) mRNA was increased in these regions by 36 to 72 h. During lactation, more variability was present in gene expression in alveolar tissue between cows and between quarters within a cow, than within quarters. Histological analysis indicated the alveolar tissue from lactating cows was mostly uniform in structure; however, in situ hybridization indicated that although most of the alveolar tissue expressed milk proteins, the level of expression varied within and between alveoli. This heterogeneity became more pronounced with involution and with increasing regions of alveoli expressing lactoferrin, indicating that alveoli enter involution asynchronously. The peripheral and cisternal tissue had more variability in gene expression between cows compared with the alveolar tissue. The M-SAA3 signal was more intense in the cisternal tissue and less intense than the peripheral compartment compared with LF particularly in the earlier time points. In addition, between cows within the later time points, differences were observed in tissue morphology, the levels of milk protein and immune-related gene expression, and phosphorylated signal transducer and activator of transcription (STAT) 5-P and STAT3-P proteins, and degree of apoptosis, indicating that involution of the mammary gland occurs at different rates between cows. Understanding the mechanisms initiating the process of involution of the mammary gland provides an opportunity for enhancing milk production of the dairy cow., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

X chromosome inactivation (XCI) is a process by which 1 of the 2 copies of the X chromosomes present in female mammals is inactivated. The transcriptional silencing of one X chromosome achieves dosage compensation between XX females and XY males and ensures equal expression of X-linked genes in both sexes. Although all mammals use this form of dosage compensation, the complex mechanisms that regulate XCI vary between species, tissues, and development. These mechanisms include not only varying levels of inactivation, but also the nature of inactivation, which can range from being random in nature to driven by parent of origin. To date, no data describing XCI in calves or adult cattle have been reported and we are reliant on data from mice to infer potential mechanisms and timings for this process. In the context of dairy cattle breeding and genomic prediction, the implications of X chromosome inheritance and XCI in the mammary gland are particularly important where a relatively small number of bulls pass their single X chromosome on to all of their daughters. We describe here the use of RNA-seq, whole genome sequencing and Illumina BovineHD BeadChip (Illumina, San Diego, CA) genotypes to assess XCI in lactating mammary glands of dairy cattle. At a population level, maternally and paternally inherited copies of the X chromosome are expressed equally in the lactating mammary gland consistent with random inactivation of the X chromosome. However, average expression of the paternal chromosome ranged from 10 to 90% depending on the individual animal. These results suggest that either the mammary gland arises from 1 or 2 stem cells, or a nongenetic mechanism that skews XCI exists. Although a considerable amount of future work is required to fully understand XCI in cattle, the data reported here represent an initial step in ensuring that X chromosome variation is captured and used in an appropriate manner for future genomic selection., (The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

Single nucleotide polymorphisms have been the DNA variant of choice for genomic prediction, largely because of the ease of single nucleotide polymorphism genotype collection. In contrast, structural variants (SV), which include copy number variants (CNV), translocations, insertions, and inversions, have eluded easy detection and characterization, particularly in nonhuman species. However, evidence increasingly shows that SV not only contribute a substantial proportion of genetic variation but also have significant influence on phenotypes. Here we present the discovery of CNV in a prominent New Zealand dairy bull using long-read PacBio (Pacific Biosciences, Menlo Park, CA) sequencing technology and the Sniffles SV discovery tool (version 0.0.1; https://github.com/fritzsedlazeck/Sniffles). The CNV identified from long reads were compared with CNV discovered in the same bull from Illumina sequencing using CNVnator (read depth-based tool; Illumina Inc., San Diego, CA) as a means of validation. Subsequently, further validation was undertaken using whole-genome Illumina sequencing of 556 cattle representing the wider New Zealand dairy cattle population. Very limited overlap was observed in CNV discovered from the 2 sequencing platforms, in part because of the differences in size of CNV detected. Only a few CNV were therefore able to be validated using this approach. However, the ability to use CNVnator to genotype the 557 cattle for copy number across all regions identified as putative CNV allowed a genome-wide assessment of transmission level of copy number based on pedigree. The more highly transmissible a putative CNV region was observed to be, the more likely the distribution of copy number was multimodal across the 557 sequenced animals. Furthermore, visual assessment of highly transmissible CNV regions provided evidence supporting the presence of CNV across the sequenced animals. This transmission-based approach was able to confirm a subset of CNV that segregates in the New Zealand dairy cattle population. Genome-wide identification and validation of CNV is an important step toward their inclusion in genomic selection strategies., (The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

Increasing environmental temperatures are a threat to the sustainability of livestock production and, because of the high metabolic demands of lactation, to dairy production in particular. Summer heat waves in temperate climates reduce feed intake, milk production, and cow comfort. In extreme heat events, there is an increase in cow mortality. In tropical climates, dairy cattle are mostly (zebu) type or zebu crossbred with temperate dairy breeds. Crossbreeding is undertaken to combine the heat tolerance and tick resistance of zebu with the productivity of temperate dairy breeds. In the absence of improved heat tolerance, milk production and fertility of temperate cattle is severely impaired. We have recently identified a key role for the prolactin pathway in regulating heat tolerance. A de novo mutation in prolactin that impairs prolactin activity was discovered in hairy and heat intolerant, New Zealand dairy cattle. The phenotypes produced were remarkably similar to those seen in fescue toxicosis, a syndrome seen in grazing cattle in the U.S. where ingestion of ergovaline, a fungal toxin from infected pasture, inhibits prolactin secretion. Recognition of the role of prolactin in hairy cattle led us to identify a deletion in exon 10 of the long-form of the prolactin receptor in Senepol cattle that causes truncation of the protein and determines the slick coat and heat tolerance traits found in this , beef breed. The short form of the prolactin receptor is predicted to be unaffected by the deletion. Knowledge of this dominant mutation has provided the impetus to begin a crossbreeding program to investigate performance and heat tolerance of temperate dairy cattle carrying the slick, prolactin receptor variant. The perceived opportunity is to introgress this variant into temperate dairy cattle to enable performance and welfare improvement in hot climates. Heat tolerance of cattle with slick coats appears to be mostly associated with coat type although sweating ability may also be enhanced. Further investigation is required of performance traits in cows homozygous for the slick variant because the published data are almost exclusively from heterozygous animals. Combination of the slick mutation with other favorable genes for heat tolerance, especially those for coat color, will be particularly enabled by gene editing technologies, offering opportunities for further improvement in bovine thermotolerance.

Objective: To investigate the prevalence of, and risk factors for, pelvic floor disorders (PFDs) in women in Bangladesh., Methods: A nationally representative sample of 1590 Bangladeshi women, aged 30-59 years, was recruited using a multistage cluster sampling technique, between September 2013 and March 2014. Urinary incontinence (UI), fecal incontinence (FI) and pelvic organ prolapse (POP) were assessed using validated questionnaires. The weighted prevalence and the factors associated with each PFD were investigated using multivariable weighted logistic regression., Results: The weighted prevalence of UI was 23.7% (95% confidence interval (CI) 21.3-26.0%), FI 5.3% (95% CI 4.0-6.6%), POP 16.2% (95% CI 14.2-18.2%), and having at least one PFD 35.3% (95% CI 32.6-37.9%). Women were more likely to have at least one PFD if aged 40-49 years (adjusted odds ratio (AOR) 1.46, 95% CI 1.02-2.08; p = 0.040) or 50-59 years (AOR 2.39, 95% CI 1.59-3.58; p < 0.0001), compared with women aged 30-39 years. Having at least one PFD was positively associated with having three or more versus fewer children (AOR 1.61, 95% CI 1.14-2.27; p = 0.007), being in the middle (AOR 3.05, 95% CI 1.72-5.41; p < 0.0001), second lowest (AOR 2.49, 95% CI 1.39-4.47; p = 0.002) or lowest (AOR 3.13, 95% CI 1.68-5.86; p < 0.0001) wealth quintile compared with the highest, and self-reporting diabetes (AOR 2.55, 95% CI 1.54-4.23; p < 0.0001)., Conclusions: One-third of Bangladeshi women aged 30-59 years had at least one symptomatic PFD. Risk factors included greater age, higher parity, lower wealth status and self-reported diabetes. The diagnosis, treatment, and prevention of PFDs in Bangladesh need greater attention, as the prevalence of these disabling conditions is likely to increase with the aging of the population.

Communicating non-urgent, urgent and frank emergency requests for assistance between anaesthetists in theatre often requires a 'go-between' - frequently a non-anaesthetic healthcare professional - to transmit information. We compared the currently recommended situation, background, assessment, recommendation (SBAR) tool with a newly devised Traffic Lights tool ('red alert', 'amber assist' and 'green query') in a simulation study to assess communication quality using 12 validated clinical scenarios of varying urgency. Compared to SBAR, Traffic Lights was used more consistently ('very clear' or 'clear' Traffic Lights 94% vs SBAR 69%); transferred information better (two or three pieces of information correctly transferred Traffic Lights 85%, SBAR 44%; and was judged to lead to greater clarity (all p < 0.0001). Message delivery time was significantly reduced (Traffic Lights 20.5 s vs SBAR 45.5 s, median (95% CI) difference 25 (19-30) s, p < 0.001). Users rated the Traffic Lights system as significantly more useful than SBAR, with 96% of participants preferring the Traffic Lights tool. Results were independent of go-between training. We recommend the adoption of this communication tool as standard practice for anaesthetic teams., (© 2016 The Association of Anaesthetists of Great Britain and Ireland.)

Lactoferrin is a multifunctional glycoprotein with a range of antimicrobial and immune-related properties that is found at >10-fold higher concentration in human milk (~1.7 g/L) relative to bovine milk (~0.15 g/L). Consumer demand is increasing for bovine lactoferrin through a wide range of nutritional and cosmetic consumer products. Increasing lactoferrin yield and concentration in bovine milk could assist in satisfying this increasing demand and may also help in increasing resistance to bovine mammary infection. Two experiments with cows in mid and late lactation were carried out to examine milking strategies to increase milk lactoferrin concentration and yield. Milking was suspended in cows normally milked twice daily, for periods of 2, 4, or 7d (mid lactation) or 2 or 4d (late lactation) after which cows were milked out and twice-daily milking resumed for 4d. In all groups, lactoferrin concentration was significantly increased during the remilking period, approaching concentrations similar to those found in human milk (~1 g/L). Lactoferrin yields were significantly higher in all treatment groups, although increasing the nonmilking period beyond 2d offered no advantage. Milk yield was lower initially after resumption of milking but recovered to preexperimental values by the fourth day of remilking in all groups, except the 4-d nonmilking group in late lactation. Milk somatic cell count was significantly elevated in all groups at the start of remilking but had substantially reduced by d 4 and reached a preexperimental level in the 2-d nonmilking group of mid-lactation cows. In summary, extended milking intervals can be used as a tool to produce a short-term increase in the concentration and yield of lactoferrin from bovine milk during established lactation, without any apparent long-term effects on milk yield and quality., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The main objectives of this study were to establish the relative value of milk yields under twice-daily milking (TDM) as a predictor of yield and yield loss under once-daily milking (ODM), and to understand the role of residual milk and udder storage capacity-related traits in regulating yield and yield loss during ODM. A Holstein-Friesian × Jersey crossbred herd was established over 2 seasons (years), as 2 individual cohorts on the same farm, managed on a pasture-based system over 4 lactations. Short-term (1-wk) ODM studies, with a starting total of 690 cows, were undertaken in mid- and late-lactation in lactation 2 and in mid-lactation in lactation 3 for each cohort. A 10-wk study of ODM performance began in mid-lactation in lactation 3, whereas lactation 4 was a full-lactation assessment of ODM. In the short-term studies, milk yield under ODM was well predicted (R(2)=0.7 to 0.8 in 5 of 6 studies) by the daily yield under TDM in the week before ODM. Yield loss (kg/d) increased with increasing milk yield and with increasing somatic cell count (SCC), although predictions were relatively poor (R(2)=0.09 to 0.30). Yield loss (%) decreased with increasing TDM yield in 3 of the 6 studies and was positively correlated with SCC during ODM. Nevertheless, ODM yield loss, in absolute or percentage terms, was a poorly repeatable trait in grazing cows. Part of the variation in yield loss percentage (30%) was positively associated with residual milk (%), measured pretrial, during measurement of functional udder capacity in lactation 3. Total production (kg of milk) over the full-lactation ODM study in lactation 4 was correlated with total production in the 10-wk trial in lactation 3 (r=0.72 and 0.63 for cohorts 1 and 2, respectively). Identifying the highest- and lowest-producing 10% of animals during the full lactation of ODM indicated that poor production was associated with high yields of residual milk (measured in lactation 3) and, conversely, high production was associated with low yields of residual milk, relative to the other 80% of animals. These same "high" and "low" production groups from lactation 4 had similar differences in performance in the earlier short-term studies and a larger or smaller percentage yield loss associated with the residual milk measurement. Breeding strategies for ODM may benefit, therefore, from greater emphasis on selecting for a low residual milk fraction to optimize milking performance. Nevertheless, the level of milk production under TDM is a strong phenotypic predictor of milk production under ODM., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: This study establishes a profile for women at midlife, referred for a dual energy X-ray absorptiometry (DXA), most likely to have osteoporosis, and from this, a pre-DXA screening tool has been developed. These findings inform much needed evidence-based guidelines for targeted and effective screening for osteoporosis and osteoporotic fracture prevention in women at midlife., Introduction: There is no consensus as to whether women at midlife should undergo screening dual energy X-ray absorptiometry (DXA) to identify osteoporosis (T-score < -2.5)., Methods: We investigated the prevalence of osteoporosis in women, aged 40-65 years, referred to 42 community-based Australian radiology centres, and identified the characteristics that best predict osteoporosis in women having a screening DXA., Results: One thousand four hundred and two women completed the study questionnaire and had DXA reports available. After excluding women with an established indication for a DXA (58 %), users of bone-specific medication (10.5 %) and cancer (7.6 %), 466 women were classified as having a screening DXA. Forty of these women had osteoporosis at the lumbar spine (n = 32, 6.9 %) or femoral neck (n = 17, 3.6 %). Three predictors of osteoporosis (postmenopausal, nonuse of hormonal therapy and body mass index) were identified and incorporated into the Monash Osteoporosis Risk Score for women at midlife (MORS). In the screened study population, the MORS had a sensitivity of 70 % and specificity of 66 %, with a positive predictive value of 16.2 % and negative predictive value of 95.9 % for osteoporosis., Conclusions: Very few women referred for a screening DXA scan will be found to have osteoporosis. The MORS, a simple decision tool, would have identified 70 % of the women in our screening DXA study population and would have eliminated over 60 % of the screening DXA studies. Hence, use of the MORS may reduce unnecessary DXA scans and facilitate identification of the majority of cases of osteoporosis in women aged 40 to 65 years.

Objective: To systematically review published articles for the prevalence of menopausal symptoms in Asian women., Methods: A comprehensive and systematic literature search was performed using MEDLINE, EMBASE, PsycINFO, CINAHL, SCOPUS and Google scholar in June 2013 to retrieve all English-language studies that included information on the prevalence of menopausal symptoms in women living in Asian countries. Risk of bias of included studies was assessed using a risk-of-bias tool explicitly designed for the systematic review of prevalence studies., Results: Twenty-three independent studies met our inclusion criteria. Physical symptoms were the most prevalent symptoms compared to psychological, vasomotor and sexual symptoms. There was a wide variation in the prevalence of all symptoms across the menopausal stages due to the differences in modes of recruitment, study design, sampling procedures, the time frame over which symptoms were assessed and use of different diagnostic or screening tools. A high level of bias was observed for both external and internal validity for most studies., Conclusion: Although there is a wide variation in the reported prevalence of menopausal symptoms, physical symptoms predominate, followed by psychological symptoms, vasomotor symptoms and sexual symptoms. Further studies of representative samples are necessary to understand whether the variations in prevalence reporting are a function of methodological issues or due to ethnic, cultural or other socioeconomic differences.

Objective: Our aim was to systematically review published articles for the prevalence of persistent estrogen depletion symptoms among women aged 65+ years., Methods: A systematic literature search of English-language publications was performed using MEDLINE, EMBASE, CINAHL, and PsycINFO. Twenty-three studies that included information on the prevalence of vasomotor and/or urogenital atrophy symptoms among older women (65 + years) met our inclusion criteria. Risk of bias of the included studies was assessed using a risk-of-bias tool explicitly designed for the systematic review of prevalence studies., Results: The available data suggest that vasomotor symptoms are experienced by a considerable proportion of older women, that symptoms of urogenital atrophy including urinary incontinence are widespread, and that women remain sexually active well into later life. A high degree of variability was observed for the prevalence of estrogen deficiency symptoms for women age 65+ years. Discrepancies in modes of recruitment, sampling procedures, time frames over which symptoms were assessed and use of different and non-validated assessment tools contributed to the inconsistencies across the published studies., Conclusion: Larger and appropriately sampled studies, employing validated questionnaires, are still needed to establish the prevalence of persistent estrogen depletion symptoms in women aged 65+ years.

Aim: This study was undertaken to determine whether metformin would ameliorate insulin resistance, reduce weight and waist circumference and improve lipids in obese, but not morbidly obese, euglycemic women., Methods: Obese women (body mass index (BMI) ≥ 30 and < 40 kg/m(2) and/or waist circumference > 88 cm), aged 35-65 were randomized (1:1) to metformin 850 mg or identical placebo, twice daily for 26 weeks. The primary outcome was the change in insulin resistance determined by the homeostasis model of assessment (HOMA-IR). Secondary outcomes included fasting insulin, glucose, weight, waist circumference and BMI., Results: Of the 125 women screened, 117 enrolled and 100 women, mean age 53 years, were included in the primary intention-to-treat analysis. Metformin resulted in statistically significant between-group difference in the change in HOMA-IR (change in median - 0.04 vs. placebo + 0.1, p = 0.018) and BMI (mean change - 1.00 kg/m(2); 95% confidence interval (CI) 1.37 to - 0.62 vs. placebo mean change 0.00; 95% CI - 0.29 to 0.28, p < 0.001). Statistically significant reductions in HbA1c (p = 0.008) and fasting insulin (p = 0.03) and a borderline decrease in high density lipoprotein cholesterol (p = 0.07) were also observed for metformin, compared with placebo. No effects were seen for waist circumference, fasting glucose or other lipids., Conclusion: Treatment of euglycemic, obese, middle-aged women with metformin 1700 mg per day reduced insulin resistance and weight compared with placebo. Further studies are needed to determine whether the use of metformin will prevent the progression of insulin resistance to type 2 diabetes mellitus in obese women.

Summary: Minimal-trauma fracture is an important issue in breast cancer survivors, especially rib fracture. The likelihood of fracture is affected by menopausal status and a diagnosis of osteoporosis prior to breast cancer. Most women reported at least one assessment of bone mineral density., Introduction: We have investigated the self-reported frequency and pattern of minimal-trauma fracture (MTF) in breast cancer (BC) survivors at least 5 years from diagnosis, along with the use of bone mineral density (BMD) assessment., Methods: This study was carried out within the Bupa Health Foundation Health and Wellbeing After Breast Cancer Study which is a questionnaire-based prospective cohort study of 1683 women diagnosed with their first invasive breast cancer between 2004 and 2006 and followed for at least 5 years., Results: One thousand two hundred and five women, who remained free of recurrence or new breast cancer, completed the fifth annual follow-up. One hundred sixty-four (13.6%) reported at least one MTF. Rib fracture was the most common (52 fractures in 46 women). Compared with women who remained pre-/peri-menopausal, either being postmenopausal at diagnosis (OR 3.53, 95% Confidence Interval (CI) 1.09-11.44, p=0.036) or changing from pre- to postmenopausal during follow-up (OR 3.97, 95% CI 1.21-13.10, p=0.023) was associated with a higher likelihood of fracture, as was having a diagnosis of osteoporosis at the time of diagnosis (OR 1.74, 95% CI 1.00-2.99, p=0.047). Most women (64.9%) reported at least one BMD assessment., Conclusions: Overall MTF is a problem for breast cancer survivors, with rib fracture a particular issue for women in our study. Both pre-existing osteoporosis and being postmenopausal are risk factors for subsequent MTF in women treated for breast cancer. Clinicians need to be mindful of fracture prevention medication in these groups.

Objectives: There is a paucity of information regarding women's expectations of medical treatment for female sexual dysfunction (FSD) and their self-appraisal of treatment outcomes. The aims of this study were to explore women's perception and expectations of treatment and their experiences of treatment for FSD using a qualitative approach., Methods: First-time attendees to an endocrinologist with the complaint of sexual difficulties were identified and were invited to take part in an in-depth interview on the same day as, but prior to, their medical consultation. Follow-up phone interview took place 3-4 months later., Results: Seventeen women, aged 26-70 years, participated in the face-to-face interview. Ten of these participated in the follow-up interview. Four major themes emerged from the women's narrative stories: (1) personal psychological distress associated with FSD, (2) concern about the adverse effect of FSD on the relationship with their sexual partner, (3) a belief in a relationship between FSD and 'hormone deficiency', and (4) an expectation of treatment, which included positive physical and sexual changes., Conclusions: Health professionals should be aware of the high degree of psychological distress that can result from FSD and consider available treatment options, which may include hormone therapy.

Objective: A number of learned societies, including the International Menopause Society, have produced position statements pertaining to the use of postmenopausal hormone therapy. These documents are highly informative but are not designed for use by primary-care physicians and nurse practitioners during routine consultations. Our aim was to produce a toolkit for practitioners that could be used during office consultations to assist them in the assessment and management of the menopause., Methods: We used clinical experience in primary care, combined with published diagnostic algorithms, positions statements from learned medical societies and relevant peer-reviewed literature to develop assessment and management algorithms relevant to the primary care of women age 40 years and older., Results: The resultant 'Practitioner's Toolkit for Managing the Menopause' comprises algorithms for the reasons why a woman might present, determination of menopausal status, key information that should be ascertained, issues that may influence treatment decision-making, hormonal and non-hormonal treatment options, symptom management and patient review, and a brief supporting document., Conclusions: We believe these algorithms and supporting document provide an accessible desktop tool for health-care practitioners caring for women at midlife. The toolkit has been endorsed by the International Menopause Society for global use.

Aim: To systematically review the published data for the prevalence and severity of menopausal symptoms in Australian women., Method: A comprehensive and systematic literature search was done using six databases to extract all English-language, peer-reviewed studies that contained information on the prevalence of menopausal symptoms among women living in Australia. Risk of bias of included studies was assessed using a risk-of-bias tool specifically designed for the systematic review of prevalence studies., Results: Eight independent studies met our inclusion criteria. There was no consistent pattern of vasomotor, psychological, physical or sexual symptom prevalence for the studies that reported symptoms across the menopausal stages. The ranges of the prevalences for the various outcomes were wide. A high level of bias was observed related to both external and internal validities for the included studies., Conclusion: The available data for the prevalence of menopausal symptoms in Australian women are not sufficient to allow conclusive findings. A large, appropriately sampled study using a validated questionnaire is needed to establish the prevalence and severity of menopausal symptoms in Australian women.

Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

Objective: There is evidence for an association between levels of urinary C-telopeptide fragments of type II collagen (uCTX-II) and risk of knee osteoarthritis (OA). The aim of this cohort study was to examine the association between uCTX-II levels and knee cartilage and bone changes in middle-aged women without clinical knee disease., Design: 140 women, aged 40-67 years, with no significant knee pain, knee injury or any forms of arthritis, underwent knee magnetic resonance imaging (MRI) at baseline and 2 years later. Cartilage volume, cartilage defects, tibial plateau bone area and bone marrow lesions (BMLs) were measured using validated methods. Baseline uCTX-II was measured using enzyme-linked immunosorbent assay (ELISA)., Results: For every one unit (natural logarithm transformed) increase in baseline uCTX-II level, there was an increase in the prevalence of medial tibiofemoral cartilage defects (Odds ratio (OR) 4.36, 95% confidence interval (CI) 1.58-12.04), medial (80.2 mm(2), 95% CI 9.3-151.1) and lateral (86.0 mm(2), 95% CI 33.3-138.7) tibial plateau bone area, and the prevalence of lateral tibiofemoral BMLs (OR 10.62, 95% CI 1.82-61.85). Baseline uCTX-II levels were not significantly associated with baseline tibial cartilage volume or changes in knee cartilage volume or defects or bone area over 2 years, although there was a trend for the deterioration of medial tibiofemoral BMLs (P = 0.06)., Conclusion: In middle-aged women without clinical knee disease, higher uCTX-II levels were associated with early detrimental structural changes at the knee (cartilage defects, tibial bone expansion and BMLs) at baseline but not over 2 years. Further work will be needed to determine its sensitivity to change and whether it predicts disease progression over longer time periods., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Although there is evidence that minimal surveillance is compatible with an optimal outcome in women after early stage breast cancer, little is known of the surveillance that these women receive., Aims: To describe the intended clinical follow up and patterns of use of imaging modalities in low-risk breast cancer survivors who are at least 5 years from diagnosis., Methods: Participants in the Bupa Health Foundation Health and Wellbeing After Breast Cancer Study with stage 1 invasive breast cancer at diagnosis, who had survived free of recurrence or new primary breast cancer for at least 5 years, provided information for this analysis., Results: The most common choice of physician follow up was with one doctor only (54%). Within this group, the most frequent choice was a general practitioner (GP) (63%) followed by medical oncologist (23%). Thirty-five per cent of women said that they intended to consult two doctors and within this group, the most common combination was a GP and a medical oncologist (45%). This was despite two out of three women reporting being advised that there was no need to consult a medical oncologist. Over 90% of women reported having a mammogram with, or without, breast ultrasound in the previous 12 months. There was a low rate of use of other imaging tests in the absence of clear indications., Conclusions: Minimising unnecessary medical consultations by women with breast cancer at low risk of recurrence 5 years from diagnosis will require education about the benefits of a minimal surveillance strategy., (© 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.)

A genomic prediction for residual feed intake (RFI) developed in growing dairy heifers (RFIgro) was used to predict and test breeding values for RFI in lactating cows (RFIlac) from an independent, industry population. A selection of 3,359 cows, in their third or fourth lactation during the study, of above average genetic merit for milk production, and identified as at least 15/16ths Holstein-Friesian breed, were selected for genotyping from commercial dairy herds. Genotyping was carried out using the bovine SNP50 BeadChip (Illumina Inc., San Diego, CA) on DNA extracted from ear-punch tissue. After quality control criteria were applied, genotypes were imputed to the 624,930 single nucleotide polymorphisms used in the growth study. Using these data, genomically estimated breeding values (GEBV) for RFIgro were calculated in the selected cow population based on a genomic prediction for RFIgro estimated in an independent group of growing heifers. Cows were ranked by GEBV and the top and bottom 310 identified for possible purchase. Purchased cows (n=214) were relocated to research facilities and intake and body weight (BW) measurements were undertaken in 99 "high" and 98 "low" RFIgro animals in 4 consecutive groups [beginning at d 61 ± 1.0 standard error (SE), 91 ± 0.5 SE, 145 ± 1.3 SE, and 191 ± 1.5 SE d in milk, respectively] to measure RFI during lactation (RFIlac). Each group of ~50 cows (~25 high and ~25 low RFIgro) was in a feed intake facility for 35 d, fed pasture-alfalfa cubes ad libitum, milked twice daily, and weighed every 2 to 3 d. Milk composition was determined 3 times weekly. Body weight change and BW at trial mid-point were estimated by regression of pre- and posttrial BW measurements. Residual feed intake in lactating cows was estimated from a linear model including BW, BW change, and milk component yield (as MJ/d); RFIlac differed consistently between the high and low selection classes, with the overall means for RFIlac being +0.32 and -0.31 kg of dry matter (DM) per day for the high and low classes, respectively. Further, we found evidence of sire differences for RFIlac, with one sire, in particular, being highly represented in the low RFIgro class, having a mean RFIlac of -0.83 kg of DM per day in 47 daughters. In conclusion, genomic prediction of RFIgro based on RFI measured during growth will discriminate for RFIlac in an independent group of lactating cows., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Residual feed intake (RFI), as a measure of feed conversion during growth, was estimated for around 2,000 growing Holstein-Friesian heifer calves aged 6 to 9 mo in New Zealand and Australia, and individuals from the most and least efficient deciles (low and high RFI phenotypes) were retained. These animals (78 New Zealand cows, 105 Australian cows) were reevaluated during their first lactation to determine if divergence for RFI observed during growth was maintained during lactation. Mean daily body weight (BW) gain during assessment as calves had been 0.86 and 1.15 kg for the respective countries, and the divergence in RFI between most and least efficient deciles for growth was 21% (1.39 and 1.42 kg of dry matter, for New Zealand and Australia, respectively). At the commencement of evaluation during lactation, the cows were aged 26 to 29 mo. All were fed alfalfa and grass cubes; it was the sole diet in New Zealand, whereas 6 kg of crushed wheat/d was also fed in Australia. Measurements of RFI during lactation occurred for 34 to 37 d with measurements of milk production (daily), milk composition (2 to 3 times per week), BW and BW change (1 to 3 times per week), as well as body condition score (BCS). Daily milk production averaged 13.8 kg for New Zealand cows and 20.0 kg in Australia. No statistically significant differences were observed between calf RFI decile groups for dry matter intake, milk production, BW change, or BCS; however a significant difference was noted between groups for lactating RFI. Residual feed intake was about 3% lower for lactating cows identified as most efficient as growing calves, and no negative effects on production were observed. These results support the hypothesis that calves divergent for RFI during growth are also divergent for RFI when lactating. The causes for this reduced divergence need to be investigated to ensure that genetic selection programs based on low RFI (better efficiency) are robust., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: The profound estrogen depletion caused by aromatase inhibitors (AIs) is associated with musculoskeletal symptoms, but the underlying pathophysiology remains unclear., Objective: To assess the effects of AI therapy on structural changes in knee cartilage and subchondral bone over 2 years in postmenopausal women. Setting and participants Thirty women with breast cancer, mean age 58.5 (standard deviation ± 5.6) years and 62 healthy controls, mean age 56.5 (standard deviation ± 4.6) years., Main Outcome Measures: Annualized changes in tibial cartilage volume and subchondral bone area, and worsening of tibiofemoral cartilage defects from paired knee magnetic resonance imaging 2 years apart were compared between the two groups., Results: The AI-treated women had significantly greater expansion of the tibial plateau than the control group. The mean annualized differences, after adjusting for age, body mass index and baseline bone area, were 22.1 mm(2) (95% confidence interval (CI) 7.6-36.6, p = 0.003) for the medial tibial plateau and 19.1 mm(2) (95% CI 9.6-28.5, p < 0.001) for the lateral tibial plateau. The annual change in tibial cartilage volume and the worsening of cartilage defects did not differ between women taking AI therapy and controls., Conclusions: AI therapy is associated with knee subchondral bone expansion knee with no effect on knee cartilage in postmenopausal women without pre-existing joint symptoms. This suggests the effect of severe estrogen depletion on knee is on bone, with the tibial bone expansion most likely a response to mechanical load in the setting of bone loss. Whether this then results in an increased risk of knee osteoarthritis will need to be determined.

Objective: The aim of this review was to summarize the literature regarding the potential role of testosterone therapy for women., Methods: The author conducted a search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2013) for English-language studies that included the following search terms: 'testosterone' or 'androgen' combined with 'women', 'therapy' or 'treatment'., Results: Randomized, placebo-controlled trials have consistently shown that transdermal testosterone therapy improves sexual desire, arousal, orgasm frequency and satisfaction in premenopausal and postmenopausal women presenting with sexual desire/arousal problems. No adverse metabolic effects have been observed in these studies. In postmenopausal women, testosterone therapy has also been associated with favorable effects on body composition, bone, cardiovascular function and cognitive performance., Conclusions: Although androgens have many varied roles, the focus of testosterone therapy for women has been on improving sexual desire. Not only do testosterone effects on sexuality extend beyond libido, but testosterone has other key physiological actions. Issues that urgently need to be addressed include approval of a testosterone formulation that delivers a female dose such that physicians refrain from prescribing compounded testosterone or modifying doses of testosterone formulated for men and regulation of prescription of compounded androgens for women.