Influence of Physical Activity Levels and Functional Capacity on Brain ß-Amyloid Deposition in Older Women.

Physical activity (PA) and Alzheimer's disease are associated. However, how PA influences the cerebral ß-amyloid (Aß) burden remains unclear. The aim of this study was to determine if PA levels and/or functional capacity (FC) are associated with Aß plaque deposition, and whether these associations differed according to APOE-ε4 genotype. A total of 117 women (69.7 ± 2.6 years; 33.3% APOE-ε4-carriers) from the Women's Healthy Ageing Project cohort (WHAP) were analyzed. PA was measured using the International Physical Activity Questionnaire and, FC was evaluated using the Timed Up and Go test (TUGt). Positron emission tomography with F-18 Florbetaben was carried out to assess cerebral Aß burden, and quantified using standardized uptake value rations. The sample was split into PA and TUGt tertiles (T1, T2 and T3), and compared according to APOE-ε4 genotype (positive/negative). There were no significant differences in Aß accumulation according to PA tertiles and APOE-ε4 genotype. Regarding FC, APOE-ε4+ participants in the first TUGt tertile (high performance) obtained significant lower Aß accumulations compared with the other two tertiles (p < 0.05). Comparing between genotypes, greater Aß depositions were found between T2 and T3 in APOE-ε4+ compared with those who were APOE-ε4- (p < 0.05). Values of TUGt ≥ 6.5 s (APOE-ε4+) and 8.5 s (APOE-ε4-) were associated with an increased risk of having higher Aß retention. In conclusion, low performance in TUGt is associated with a negative effect on brain pathology with increasing cerebral Aß depositions in older women who are APOE-ε4+. In physically active older women (> 600 METs·min/week), higher PA levels are not associated with reduction in Aß depositions.

Mid-life predictors of late-life depressive symptoms; determining risk factors spanning two decades in the Women's Heathy Ageing Project.

BACKGROUND: Data available from longitudinal studies of adequate duration to explore midlife risk factors for late life higher depressive symptom scores in women is lacking. This study examines midlife (mean ages 50 years and 60 years) predictors of late life (mean age 70 years) depressive symptom scores to enrich our understanding of the role of changing risk factors across the lifespan. METHODS: This investigation was an assessment of the long-term impact of lifestyle and health variables on depressive symptoms. Data were drawn from an epidemiological prospective study of women's healthy ageing spanning two decades. Variables included assessment of mood, demographics, physical health, smoking status, attitudes towards ageing and menopause, alcohol consumption and employment. Analysis was conducted to determine the set of strongest predictors assessed in 1992 (mean age 50 years) and in 2002 (mean age 60 years) in relation to higher CESD-SF scores measured in 2012 (mean aged 70 years (n = 249)). A cross-sectional analysis determining concurrent associations at mean age 70 years was also conducted. RESULTS: An increase in positive mood at 50 and 60 years was associated with a 0.3 (95% CI 0.1-0.5) and 0.4 (95%CI 0.1-0.8) point reduction in CESD score at 70 years respectively. An increase in Hassles score at age 50 was associated with a 0.18-point increase in CESD (95% CI 0.01-0.05) 20 years later. However, no relationship was observed between Hassles score at 60 and CESD 10 years later. Analysis of concurrent risk factors demonstrated that bothersome symptom frequency and higher anxiety were associated with higher depressive symptom scores when women were 70 years. CONCLUSION: Low levels of positive mood were consistently associated with depressive symptoms scores 10 and 20 years later, suggesting clinical interventions aimed at improving positive affect may be particularly useful across the midlife.

Longitudinal nutritional changes in aging Australian women.

BACKGROUND AND OBJECTIVES: The importance of diet for the maintenance of health during aging is attracting a growing body of research interest. Given dietary intakes, along with BMI, are substantial contributors to disease burden, this study aimed to investigate prospective changes in dietary patterns and nutrient intakes in a sample of mid to late-life women over 14 years. METHODS AND STUDY DESIGN: Participants were from the Women's Healthy Ageing Project (WHAP); a longitudinal cohort of Australian-born women within the Melbourne metropolitan area. 173 participants were included in this analysis, their mean age in 1998 was 55 years (range 51-62) and in 2012 was 70 years (range 66-76). Diet was assessed using the Dietary Questionnaire for Epidemiological Studies Version 2 in 1998 and 2012. Nutritional intakes, Dietary Inflammatory Index (DII®) scores, Mediterranean Diet (MD) scores, sociodemographic and physical measures were calculated for all participants at both time points. RESULTS: Energy intake was found to significantly decrease over time (p<0.005). Energy-adjusted (i.e., energy density) total fat, saturated fat, monounsaturated fat and cholesterol intakes increased over time (all p<0.002), while energy-adjusted and absolute carbohydrate intake decreased (p<0.002). Adherence to the MD decreased over time (p<0.001) whilst DII scores increased slightly over time, although this result was not significant. CONCLUSIONS: This study shows significant changes in the intake of energy and several nutrients in a cohort of aging Australian women in the Melbourne metropolitan area over a period of 14 years. Between 1998 and 2012, changes in indices reflecting overall diet were consistently in the direction of a poorer diet.

Robust norms for neuropsychological tests of verbal episodic memory in Australian women.

OBJECTIVE: Robust norms for neuropsychological tests may offer superior clinical utility to conventional norms, in their ability to distinguish normal cognitive aging from prodromal dementia. However, the availability of robust norms from midlife, where cognitive changes in those at risk of disease may arise, is limited. This study presents demographically stratified robust norms for tests of verbal memory in Australian women. METHOD: Participants were from the population-based Women's Healthy Ageing Project. Baseline (1999 to 2002; n = 368; age range = 53-67years) and follow-up (2012 to 2014; n = 291; age range = 65-80years) measures of word-list and story recall were administered at least 10 years apart. Four samples were identified: conventional (derived from a cross-sectional sample), robust (derived from a longitudinal sample), mild cognitive impairment (MCI) or Alzheimer's disease (AD), and lost to follow-up. Area under the curve (AUC) values were generated to assess the diagnostic ability of conventional and robust norms using 1 standard deviation and 1.5 standard deviation cut-offs. RESULTS: There were differences between conventional Australian and American normative data for the Consortium to Establish a Registry for Alzheimer's Disease word-list recall. Individuals who declined to MCI/AD over the follow-up displayed poorer performance at baseline, however no differences in classification ability of robust (AUC range .54 to.64) and conventional (AUC range .51 to .65) norms were observed. CONCLUSION: Neuropsychological performance in midlife predicted clinical cognitive decline 1 decade later, but conventional and robust norms was similarly predictive of conversion to disease in this cohort. The use of country-specific, representative conventional norms remains a valuable tool for neuropsychologists to assess cognitive performance throughout midlife. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Apolipoprotein E4 Mediates the Association Between Midlife Dyslipidemia and Cerebral Amyloid in Aging Women.

Cerebral amyloid-ß (Aß) plaques are the hallmark biomarker of Alzheimer's disease (AD) and are detectable decades before clinical symptoms. Modifying risk factors associated with Aß accrual offers an opportunity for AD prevention. While midlife vascular health is linked to AD; there is minimal longitudinal evidence regarding the effect of midlife lipids on Aß. We examined the association between midlife lipids and Aß 20 years later. One hundred and twenty-two women had serum lipid profiles in midlife (1992, 45-57 years), and cerebral imaging, genotyping, and cognition measured 20 years later (2012/13, 66-77 years). Imaging was performed in 2012/13 via F-18 Florbetaben positron emission tomography (PET) and standard uptake value ratios (SUVR) were calculated. Lipid profiles and other predictors of high PET-SUVR levels (>1.2) were evaluated using multivariable logistic regression. Increases in low-density lipoprotein (LDL) cholesterol in midlife were associated with Aß, adjusting for age, education, cholesterol medication, and cognition (AdjOR1.81, 95% CI 1.08-3.01, p = 0.024), but attenuated on adjustment for apolipoprotein E4 (APOE ɛ4). Aß risk increased in women with APOE ɛ4 and midlife cholesterol >6.2 mmol/L (AdjOR9.59, 95% CI 2.94-31.31, p < 0.001), APOE ɛ4 and LDL >3.3 mmol/L (AdjOR9.00, 95% CI 2.89-28.03, p < 0.001), and APOE ɛ4 and cholesterol to high-density lipoprotein ratio ≥3.25 (AdjOR8.32, 95% CI 2.32-29.89, p < 0.001). Presence of APOE ɛ4 and midlife dyslipidemia compounded the risk for Aß deposition, although no independent effect of midlife lipids was found. Lipid-modifying treatment in midlife could mitigate the risk of Aß in women with a genetic predisposition for AD. To better inform prevention, future consideration should be given toward managing dyslipidemia in women carrying the APOE ɛ4 allele.

Dietary patterns and ß-amyloid deposition in aging Australian women.

INTRODUCTION: Evidence indicates that associations between diet and Alzheimer's disease may occur through biomarker pathways such as amyloid-ß (Aß); however, few studies have investigated dietary/Aß relationships, and no study has investigated this relationship in women. METHODS: Dietary patterns were extrapolated for 115 participants from the Women's Health Aging Project. Aß deposition was measured via in vivo F-18 florbetaben positron emission tomography scanning. RESULTS: Participants were, on average, aged 70 years (±2.63 SD), had 13 years of education (±3.57 SD), a BMI of 28 kg/m2 (±5.46 SD), and a daily energy intake of 5161 kJ (±1679.03 SD). Four dietary patterns were identified: high fat, Mediterranean, junk food, and low fat. Adherence to the junk food diet was a significant predictor of Aß deposition (ß = .10, P = .03). DISCUSSION: This study highlights the potential of diet to influence neurodegenerative disease and as a potential modifiable lifestyle risk factor for Alzheimer's disease.

Vitamin D status is associated with executive function a decade later: Data from the Women's Healthy Ageing Project.

OBJECTIVES: Vitamin D deficiency has been associated with cognitive decline and dementia in older adults. However, there is a paucity of studies assessing whether this association manifests from midlife. Given the long prodromal stage of dementia, we investigated the association between midlife vitamin D and cognition 10 years later. STUDY DESIGN: 252 participants (aged 55-67 years) from the Women's Healthy Ageing Project had baseline (2002) vitamin D and neuropsychological measures assessed. Of these, 170 (aged 65-77 years) had follow-up neuropsychological testing (2012). OUTCOME MEASURES: Serum 25-hydroxyvitamin D (25[OH]D) was measured using an automated chemiluminescence system. The neuropsychological tests used were: Consortium to Establish a Registry for Alzheimer's Disease (CERAD), California Verbal Learning Test Second Edition (CVLT-II), verbal fluency and Trail Making Test-B (TMT-B). Composite scores for verbal episodic memory (CERAD and CVLT-II) and executive function (verbal fluency and TMT-B) were obtained by summating standardized scores for each test. RESULTS: Analyses were adjusted for age, education and body mass index (BMI). Further adjustment for physical activity, depression, vascular risk factors, supplementation and APOE4-genotype did not materially change the results. At baseline, those with vitamin D>25nmol/L performed better on verbal fluency (ß=2.46, 95%CI=0.53,4.40) and TMT-B time (ß=-18.23, 95%CI=-32.86,-3.61), with higher executive function (ß=1.40, 95%CI=0.44,2.37). These relationships persisted 10 years later for TMT-B (ß=-15.38, 95%CI=-30.82,0.07) and executive function (ß=1.05, 95%CI=0.14,1.95). There were no associations with tests of verbal episodic memory. CONCLUSION: Midlife vitamin D>25nmol/L is associated with improved aspects of executive function in ageing. Findings highlight a potential therapeutic age window where midlife vitamin D repletion could be neuroprotective against cognitive decline.

Correction: Unhealthy habits persist: The ongoing presence of modifiable risk factors for disease in women.

[This corrects the article DOI: 10.1371/journal.pone.0173603.].

Unhealthy habits persist: The ongoing presence of modifiable risk factors for disease in women.

OBJECTIVES: Vascular disease remains a leading cause of death. There are several vascular risk factors identified that can mitigate development of disease in ageing. We examine reported rates of modifiable risk factors in women responding to an online health questionnaire advertised by popular media. METHODS: A sample of 26 620 women aged over 18 was examined in 2015 with a cross-sectional health questionnaire. The questionnaire included self-reported health, mood, lifestyle and vascular risk factors. RESULTS: There remains high rates of modifiable risk factors present in women. The vast majority of women (80%) reported not eating enough fruit and vegetables. Compared to the guidelines for health, the majority did not perform enough weekly physical activity (70%) and more than half the participants were overweight (54%). Sufficient fruit, vegetables, fish, legumes and physical activity were reported in less than 30% of women! CONCLUSIONS: Women continue to report low rates of physical activity, fruit and vegetable intake and higher BMI than recommended for good health, despite worldwide health promotion activities aimed at changing these lifestyle factors. Programs to support healthy living need to be reviewed and revised to reduce the burden of vascular disease and dementia in women. Previous guidelines are not having the important impact they should, particularly in women.

Impact of menopausal status on negative mood and depressive symptoms in a longitudinal sample spanning 20 years.

OBJECTIVE: Studies examining depressive symptoms and negative mood across the postmenopause are lacking, particularly those that examine prevalence in early and late postmenopause. This study examines negative mood and depressive occurrence in the menopausal stages to provide a better understanding of prevalence of mood disturbance during this period. METHODS: This study was a longitudinal assessment of variables drawn from an epidemiological prospective study of women's healthy aging. Scores were analyzed using general linear mixed models to determine whether there were reductions in negative mood across the stages of the menopausal transition, including the substages of the early and late postmenopause, as defined by Stages of Reproductive Ageing Workshop+10 criteria. Negative mood scores, derived from the Affectometer 2, were obtained at 11 time points between 1992 and 2012 in a group of 438 Melbourne-based, community-dwelling women aged between 45 and 55 years at baseline (n = 234; 53% retention in 2012). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale administered at three time points for 10 years. RESULTS: Women's experience of negative mood and depressive symptoms was highest during the menopausal transition and lowest in the late postmenopause. Increasing age was associated with a reduction in depressive symptoms F(1,559) = 14.83, P < 0.001 and negative mood F(1,935) = 14.97, P < 0.001. When controlling for age, there was no difference found between the early and late postmenopause stage mean scores. CONCLUSIONS: Although there were differences found between negative mood and depressive symptom scores in relation to categories of reproductive aging, age was found to be the driving influence to their association.

The trajectory of negative mood and depressive symptoms over two decades.

OBJECTIVE: Research aimed at understanding the temporal characteristics of depressive symptoms and negative mood in an older female population is lacking, despite the relationship between the two factors being well established. The aim of this study was to examine the characteristics of negative mood scores and depressive symptom scores in a longitudinal sample of women transitioning from mid-life to late life. STUDY DESIGN: This study was a longitudinal assessment of variables drawn from an epidemiological prospective study of women's healthy ageing. Scores were analysed using General Linear Mixed Models. MAIN OUTCOME MEASURES: Negative mood scores derived from the Affectometer 2 were assessed at 11 time points spanning 20 years. Depressive symptom scores were assessed using the Centre for Epidemiological Studies Depression Scale (CESD), administered in 2002, 2004 and 2012. RESULTS: Mean negative mood scores reduced significantly between 1992 and 2012, as did mean CESD scores between 2002 and 2012. Mean negative mood scores reduced by 0.007 for each year of increasing age. For depressive symptoms, a reduction in mean score of 0.15 was found for each year of increase in age. CONCLUSION: Depressive symptom scores and negative mood scores decreased significantly over time.

Predictive Factors for Verbal Memory Performance Over Decades of Aging: Data from the Women's Healthy Ageing Project.

BACKGROUND: Abnormalities in brain structure and function can occur several decades prior to the onset of cognitive decline. It is in the preceding decades that an intervention is most likely to be effective, when informed by an understanding of factors contributing to the disease prodrome. Few studies, however, have sufficient longitudinal data on relevant risks to determine the optimum targets for interventions to improve cognition in aging. In this article we examine the timing and exposure of factors contributing to verbal memory performance in later life. METHODS: 387 participants from the population-based Women's Healthy Ageing Project, mean age at baseline of 49.6 years (range: 45-55 years), had complete neuropsychiatric assessments, clinical information, physical measures, and biomarkers collected at baseline, with at least three follow-up visits that included at least one cognitive reassessment. Mixed linear models were conducted to assess the significance of risk factors on later-life verbal memory. We explored the influence of early, contemporaneous, and cumulative exposures. RESULTS: Younger age and better education were associated with baseline memory test performance (CERAD). Over the 20 years of study follow-up, cumulative mid- to late-life physical activity had the strongest effect on better later life verbal memory (0.136 [0.058, 0.214]). The next most likely contributors to verbal memory in late life were the negative effect of cumulative hypertension (-0.033 [-0.047, -0.0.18] and the beneficial effect of HDL cholesterol (0.818 [0.042, 1.593]). CONCLUSIONS: Findings suggest that midlife interventions focused on physical activity, hypertension control, and achieving optimal levels of HDL cholesterol will help maintain later-life verbal memory skills.

Diagnosing Sexual Dysfunction in Men and Women: Sexual History Taking and the Role of Symptom Scales and Questionnaires.

INTRODUCTION: A detailed sexual history is the cornerstone for all sexual problem assessments and sexual dysfunction diagnoses. Diagnostic evaluation is based on an in-depth sexual history, including sexual and gender identity and orientation, sexual activity and function, current level of sexual function, overall health and comorbidities, partner relationship and interpersonal factors, and the role of cultural and personal expectations and attitudes. AIM: To propose key steps in the diagnostic evaluation of sexual dysfunctions, with special focus on the use of symptom scales and questionnaires. METHODS: Critical assessment of the current literature by the International Consultation on Sexual Medicine committee. MAIN OUTCOME MEASURES: A revised algorithm for the management of sexual dysfunctions, level of evidence, and recommendation for scales and questionnaires. RESULTS: The International Consultation on Sexual Medicine proposes an updated algorithm for diagnostic evaluation of sexual dysfunction in men and women, with specific recommendations for sexual history taking and diagnostic evaluation. Standardized scales, checklists, and validated questionnaires are additional adjuncts that should be used routinely in sexual problem evaluation. Scales developed for specific patient groups are included. Results of this evaluation are presented with recommendations for clinical and research uses. CONCLUSION: Defined principles, an algorithm and a range of scales may provide coherent and evidence based management for sexual dysfunctions.

Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder.

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

Patterns of social engagement in the transition to later life.

UNLABELLED: As social roles in later life are shaped by significant life events and changes occurring in the late-life transition, examining social engagement in midlife may provide a context for interpreting the ageing social identity. This is particularly important for women, who are heavily dependent on social relationships and are more influenced by social losses and change. OBJECTIVE: To examine major social changes occurring in the decade prior to late-life, starting from approximately 45-55 years of age. STUDY DESIGN: The study accessed data from the longitudinal prospective Women's Healthy Ageing Project (WHAP). Participants were 493 women who had completed at least one assessment in the first 12 years of the study. RESULTS: Living with a partner was common and stable amongst participants, while the proportion with children still at home decreased markedly (79-44%). Full-time employment also decreased as participants approached the average retirement age (40-13%). Volunteer work was popular throughout the study, increasing slightly with age, and minding grandchildren was common at the end of the study period (80%). CONCLUSIONS: Taken together, these findings suggest a notable deficit in participants' social lives as they transition into later life, but with some evidence of compensation by increasing other social activities.

Cohort profile: Women's Healthy Ageing Project (WHAP) - a longitudinal prospective study of Australian women since 1990.

BACKGROUND: The cohort was commenced to examine women's health from midlife (45-55 years) before the menopausal transition and into ageing. METHODS: Randomised selection and assessment of 2,001 women living in the Melbourne metropolitan area was conducted by the Roy Morgan Centre in 1990/91. Of the 779 women who met the entry criteria for the longitudinal follow-up (aged 45-55 years, menstruating, having a uterus and at least one ovary and not taking hormone therapy) 438 agreed to be seen annually across the menopausal transition from 1992 to 1999. Longitudinal prospective follow-up since 2000 has continued intermittently (2002/03, 2004/05, 2012/13, 2014/15). Data collection has included fasting biomarkers in each year since 1992, clinical assessment, lifestyle and quality of life data, physical measures and validated questionnaire data. Participants have consented to data linkage and, to date, mammogram and BioGrid data have been accessed. Biobank storage including serum, deoxyribonucleic acid (DNA) storage and PAXgene tubes are maintained. DISCUSSION: The WHAP has contributed to over 200 published research findings, several books, and book chapters in a variety of areas, including: health and wellbeing; mental and cognitive health; bone health; lifestyle, vascular risk and prevention; women's health and hormonal transition; and cross-cultural research.With all participants now aged over 70 years, the cohort is ideally placed to answer key questions of healthy ageing in women. With more than 25 years of longitudinal prospective follow-up this Australian dataset is unique in its duration, breadth and detail of measures including clinical review and specialized disease-specific testing and biomarkers. Ongoing follow-up into older ages for this long-running cohort will enable the association between mid to late-life factors and healthy ageing to be determined. This is particularly valuable for the examination of chronic diseases which have a 20-30 year prodrome and to provide knowledge on multiple morbidities. The dataset has a unique opportunity to improve our understanding of temporal relationships and the interactions between risk factors and comorbidities.

Prehypertension in midlife is associated with worse cognition a decade later in middle-aged and older women.

BACKGROUND: previous studies raised the possibility that adverse health effects associated with elevated blood pressure (BP) begin at prehypertension levels (BP = 120-139/80-89 mmHg), yet few studies have examined the effects of prehypertension on cognitive functioning. OBJECTIVE: to examine the relationship between BP categories and cognitive functions in middle-aged and older women. SUBJECTS AND METHODS: two hundred and forty-seven women from the Women's Healthy Ageing Project had their BP measured twice, at mean ages 50 and 60 years. Tests of executive function, processing speed and verbal episodic memory were also administered at follow-up. Analyses of co-variance were performed to evaluate the associations between BP categories and cognitive performance. RESULTS: prehypertensive BP at age 50 years is a significant predictor of reduced processing speed and verbal episodic memory a decade later. Cross-sectional measurements at age 60 years showed that untreated hypertensive women performed significantly worse on verbal episodic memory compared with their prehypertensive peers. CONCLUSION: hypertension is a modifiable cardiovascular risk factor, and our results suggest that reducing midlife BP, even at prehypertensive levels, may be an effective prevention strategy to reduce risk for subsequent cognitive decline in middle-aged and older women.

The course of depressive symptoms during the postmenopause: a review.

As the Australian population ages, significantly more women are entering the postmenopausal stage of the climacteric, yet research focusing on the prevalence of depressive symptoms in this stage of ovarian ageing is scarce. This review will examine the information provided by studies that have a cohort with data of adequate duration to explore depressive symptom prevalence in the early and late postmenopause. Longitudinal epidemiological studies of women transitioning through the postmenopause that included measures of mood and/or depressive symptoms were identified through searches of MEDLINE (1980-2014) and PsycINFO (1980-2014) databases. Population based studies with at least two time points of assessment were included. Longitudinal studies of ageing that did not categorise women as postmenopausal were not included, as this was outside the scope of this review. Prevalence estimates of depressive symptoms varied between studies and ranged from 8.5 % to 25.7 % with percentages between 22 and 25 % being most consistently reported. Surgical postmenopause groups reported higher ratings of depressive symptoms at 18-42 % and higher incidence of major depressive disorder in all but one study. The prevalence of Major Depressive Disorder also varied with ranges from <1 % to 42 % reported. Wide ranges in prevalence were reported in the literature. Differences in definitions, inconsistent sample sizes and varying measures make it difficult to compare results across studies. The specific inclusions and exclusions of sub-samples of larger cohorts are at times inconsistent with epidemiological acquisition and, as such, impact upon generalizability of results to a healthy population.

Qualitative cross-cultural exploration of breast symptoms and impacts associated with hormonal treatments for menopausal symptoms to inform the development of new patient-reported measurement tools.

To explore cross-cultural experiences of women taking estrogen plus progestin therapies (EPT) and develop a symptom-based electronic diary and impact questionnaire for EPT-related breast symptoms. (1) Concept elicitation interviews were conducted with women in the US (n=14), Italy (n=15), Mexico (n=15) and China (n=15) to explore breast symptoms associated with EPT. Patients completed the Breast Sensitivity Questionnaire (BSQ) to evaluate understanding and comprehensiveness. (2) Based on concept elicitation, a 6-item eDiary (Breast Pain/Tenderness Daily Diary - BPT-DD) was generated and the BSQ modified forming the 18-item Breast Sensations Impact Questionnaire (BSIQ). (3) The measures were pilot-tested and then cognitively debriefed with US women receiving EPT. All qualitative data was subject to thematic analysis. Concept elicitation identified breast pain/tenderness, swollen breasts and sensitivity to contact as important symptoms, impacting women's emotional well-being, relationships with family/friends, social life, sleep, ability to move freely, contact, clothing and sexual activity. Experiences were relatively consistent across the country samples. Based on pilot testing and cognitive debriefing, the BPT-DD was reduced to 4 items (and renamed the Breast Pain Daily Diary - BP-DD) and the BSIQ was reduced to 13 items due to conceptual redundancy. Women taking EPT in the US, China, Mexico and Italy reported breast sensations that have a detrimental impact on quality of life. Two new measures were developed to assess the severity and impact of breast pain specific to EPT. This work highlights that EPT-related symptoms should be part of treatment decision-making, and treatments with less burdensome side effects are needed.