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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).

Cerebral amyloid-β (Aβ) plaques are the hallmark biomarker of Alzheimer’s disease (AD) and are detectable decades before clinical symptoms. Modifying risk factors associated with Aβ 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 Aβ. We examined the association between midlife lipids and Aβ 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 Aβ, 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). Aβ risk increased in women with APOE ɛ4 and midlife cholesterol >6.2 mmol/L (AdjOR9.59, 95% CI 2.94–31.31, p 3.3 mmol/L (AdjOR9.00, 95% CI 2.89–28.03, p

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.

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.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.Energy intake was found to significantly decrease over time (p0.005). Energy-adjusted (i.e., energy density) total fat, saturated fat, monounsaturated fat and cholesterol intakes increased over time (all p0.002), while energy-adjusted and absolute carbohydrate intake decreased (p0.002). Adherence to the MD decreased over time (p0.001) whilst DII scores increased slightly over time, although this result was not significant.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.

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.

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.

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.

Introduction Evidence indicates that associations between diet and Alzheimer's disease may occur through biomarker pathways such as amyloid-β (Aβ); however, few studies have investigated dietary/Aβ 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. Aβ 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 Aβ deposition (β = .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., Highlights • This is the first study to investigate dietary/cerebral Aβ relationships in women only. • Four dietary patterns extrapolated by principal component analysis. • Adherence to the junk food pattern is a significant predictor of Aβ deposition. • These findings support the notion of diet as a modifiable risk factor for AD.

BACKGROUND: Research has indicated the neuroprotective potential of the Mediterranean diet. Adherence to the Mediterranean diet has shown preventative potential for Alzheimer's disease incidence and prevalence, yet few studies have investigated the impact of Mediterranean diet adherence on the hallmark protein; beta-amyloid.OBJECTIVES: To investigate the association between Mediterranean diet adherence and beta-amyloid deposition in a cohort of healthy older Australian women.DESIGN: This study was a cross-sectional investigation of participants from the longitudinal, epidemiologically sourced Women's Healthy Ageing Project which is a follow-up of the Melbourne Women's Midlife Health Project.SETTING: Assessments were conducted at the Centre for Medical Research, Royal Melbourne Hospital in Melbourne, Australia. F-18 Florbetaben positron emission tomography scanning was conducted at the Austin Centre for PET in Victoria, Australia.PARTICIPANTS: One hundred and eleven Women's Healthy Ageing Project participants were included in the study.MEASUREMENTS: Mediterranean diet adherence scores for all participants were calculated from the administration of a validated food frequency questionnaire constructed by the Cancer Council of Victoria. Beta-amyloid deposition was measured using positron emission tomography standardised uptake value ratios.RESULTS: Gamma regression analysis displayed no association between Mediterranean diet adherence and beta-amyloid deposition. This result was consistent across APOE-epsilon 4 +/-cohorts and with the inclusion of covariates such as age, education, body mass index and cognition.CONCLUSIONS: This study found no association between adherence to the Mediterranean diet and beta-amyloid deposition in a cohort of healthy Australian women. Refereed/Peer-reviewed

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 (β=2.46, 95%CI = 0.53,4.40) and TMT-B time (β=-18.23, 95%CI = −32.86,−3.61), with higher executive function (β=1.40, 95%CI = 0.44,2.37). These relationships persisted 10 years later for TMT-B (β=-15.38, 95%CI = −30.82,0.07) and executive function (β=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.

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.

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.

OBJECTIVE Preserving aging cognition improves quality of life and delays dementia onset. Previous studies have shown that social engagement can maintain cognition; however, none has examined the effects of grandparenting, an important role among postmenopausal women. This study aims to examine the role of grandparenting in cognition among postmenopausal women. METHODS Participants were 186 Australian women from the longitudinal prospective Women's Healthy Aging Project. Cognition was assessed using the Symbol-Digit Modalities Test (SDMT), California Verbal Learning Test, and Tower of London. RESULTS Amount of time spent minding grandchildren predicted differences in SDMT performance (P < 0.01). The highest cognitive scores for most tests were seen in participants who minded grandchildren for 1 day/week. Minding grandchildren for 1 day/week was also a significant positive predictor of California Verbal Learning Test immediate recall performance (P < 0.05). However, minding grandchildren for 5 days or more per week predicted lower SDMT performance (P < 0.05). CONCLUSIONS The data suggest that the highest cognitive performance is demonstrated by postmenopausal women who spend 1 day/week minding grandchildren; however, minding grandchildren for 5 days or more per week predicts lower working memory performance and processing speed. These results indicate that highly frequent grandparenting predicts lower cognitive performance.

Objectives To understand the vaginal bleeding/spotting experiences of postmenopausal (PM) women taking estrogen plus progestin therapies (EPT) and develop measures to assess these symptoms and their impact on women's daily lives in four countries. Design (1) Concept elicitation interviews were conducted with PM women in the US ( n = 14), Italy ( n = 15), Mexico ( n = 15) and China ( n = 15) to explore vaginal bleeding/spotting symptoms associated with EPT. The Post-Menopausal Bleeding Questionnaire (PMBQ) was also debriefed to evaluate understanding and comprehensiveness. (2) Based on concept elicitation, a single item electronic daily diary was developed and the PMBQ modified to form a 12-item impact measure. (3) The measures were pilot-tested and then cognitively debriefed with US women receiving EPT. All qualitative data was subject to thematic analysis. Main outcome measures The Vaginal Bleeding/Spotting Daily Diary, (VBS-DD) and Post-Menopausal Bleeding Impact Questionnaire (PMBIQ) were developed in this study. Results Concept elicitation identified vaginal bleeding and spotting as important symptoms for women taking EPT, impacting their emotional wellbeing, social life, ability to move freely, clothing and sexual activity. Based on pilot testing and cognitive debriefing, women demonstrated good understanding of the VBS-DD and the PMBQ was reduced to 10 items due to conceptual redundancy. Conclusions Women taking EPT in the US, China, Mexico and Italy reported vaginal bleeding/spotting symptoms that have a detrimental impact on their quality of life. Two new measures were developed to assess the severity and impact of vaginal bleeding/spotting specific to EPT. This work highlights the need for EPT-related symptoms to be a part of treatment decision-making.

The Tower of London (TOL) task is a well-known neuropsychological measure of planning ability that is widely used in clinical and research contexts. Despite its popularity and recognised validity, clinical use of the TOL task has been limited in the adult population due to lack of comprehensive normative data. As a result, this measure has principally been employed in the clinical setting as a qualitative measure of planning skills. In this study, the TOL task was administered as part of a comprehensive neuropsychological battery to 243 healthy, Australian women (M age = 60 years, range = 56–67 years) who have been participating in the Women's Healthy Ageing Project. Results showed significant correlations between age and the total TOL score but not other outcome measures; level of education and mood were unrelated to performance on the TOL. Further analyses showed significant correlations between the TOL outcome measures and other recognised measures of executive function and working memory. The current study presents previously unavailable normative data for different aspects of the TOL performance in Australian midlife women, which may serve as a reference for more accurate clinical interpretation of the TOL in the Australian context and improve its clinical utility in the adult population.

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. Electronic supplementary material The online version of this article (doi:10.1186/s40695-016-0018-y) contains supplementary material, which is available to authorized users.

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.

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.

The aim of this paper is to review published literature on the types and prevalences of premenstrual disorders and symptoms, and effects of these on activities of daily life and other parameters of burden of illness. The method involved review of the pertinent published literature. Premenstrual disorders vary in prevalence according to the definition or categorization. The most severe disorder being premenstrual dysphoric disorder (PMDD) affects 3–8% of women of reproductive age. This disorder focuses on psychological symptoms whereas global studies show that the most prevalent premenstrual symptoms are physical. Both psychological and physical symptoms affect women's activities of daily life. A considerable burden of illness has been shown to be associated with moderate to severe premenstrual disorders. In conclusion, premenstrual symptoms are a frequent source of concern to women during their reproductive lives and moderate to severe symptoms impact on their quality of lives.

Objectives. To determine patterns of premenstrual symptom experiences across the reproductive age range, and the effects of other factors on premenstrual symptoms. Study design. Global cross-sectional survey. Sample. A total of 7226 women aged 15–49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. Main outcome measures. Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables. Results. Four different patterns of premenstrual symptoms were found with ageing: symptoms showing no change with age, symptoms decreasing with age, symptoms reaching a maximum just before or around age 35, and symptoms reaching a maximum around age 40–44. Smoking was associated with an increase in most of the premenstrual symptoms. Increasing parity was associated with a decrease in some of the symptoms. Conclusions. These results suggest that the premenstrual symptoms most associated with the years of regular ovulatory cycles are skin disorders, lack of energy, appetite problems, joint/muscle/back pain, anger, abdominal bloating, depressed mood and irritability. Other symptoms which peaked later (swelling of extremities, breast tenderness/pain, weight gain) may reflect exacerbation by hormonal changes of the late reproductive/early menopausal transition. Smokers report more problematic premenstrual symptoms.

Hormone replacement therapy (HRT) is used for relief of symptoms related to the menopause and for the prevention of postmenopausal osteoporosis and cardiovascular disease. Patterns of use of HRT are thought to be changing rapidly, but little is known about who is using the therapy, for what purpose or for what period of time. Telephone interviews were conducted in May 1991 with a randomly selected sample of 2001 Australian-born women aged 45 to 55 years living in Melbourne, as part of the Melbourne Women's Midlife Health Project. Questions related to use of HRT, health status, use of health services, sexual functioning, attitudes to menopause and aging, and sociodemographic characteristics. Twenty-one per cent of the sample were using HRT. Use was more prevalent among women 50 years and over (28 per cent) than those under 50 (15 per cent). Seventeen per cent of nonhysterectomised women, 31 per cent of hysterectomised women and 49 per cent of women who had undergone hysterectomy and bilateral oophorectomy were current users. Almost 60 per cent had been using the therapy for two years or less, and 34 per cent for one year or less. Just over half reported control of hot flushes as a benefit, and 10 per cent mentioned prevention of bone loss as a benefit. Logistic regression analysis identified differences between users and nonusers in experience of hot flushes, health status, use of preventive and treatment services, sexual functioning, wellbeing, attitudes to menopause and aging, and sociodemographic characteristics. These differences may relate to risk of later cardiovascular disease.

To evaluate the impact of premenstrual symptoms on activities of daily life (ADL) of Korean women, and their knowledge and treatment seeking regarding premenstrual syndromes (PMSs).A population-based online survey regarding premenstrual symptoms was conducted in 1000 Korean women aged 15-49 years. Symptoms were classified according to their intensity, persistence each cycle, and impairment of ADL. Women's knowledge of PMSs and physician consultations were assessed.The approximate prevalence of PMS/premenstrual dysphoric disorder (PMDD) by the WHO's International Classification of Disease (ICD-10), American College of Obstetrics and Gynecology (ACOG), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV[4th edition]) criteria was 98.6, 32.1, and 2.8%, respectively. Among 23 documented symptoms, the most predominant symptoms were joint-muscle-back pain, abdominal pain, and irritability. Physical symptoms were more prevalent than mental symptoms. There was a high correlation between the duration and severity of symptoms. The impact of PMS on ADL and the proportion of women with impaired ADL were significantly associated with the severity of PMS. The proportion of women consulting physicians increased with severity of PMS from 2%, 2.3%, for ICD-10, ACOG PMS to 10.7% for DSM-IV PMDD, respectively. Most of the women (91.5%) had no knowledge regarding terminology pertaining to PMS and PMDD.PMSs occur frequently and have a significant impact on daily life for a proportion of Korean women. However, Korean women have little knowledge about PMSs and only infrequently consult their physicians.

ObjectivesDetermine women's experiences of premenstrual symptoms.Study designCross-sectional survey.SampleIn all, 4085 women aged 14–49 years recruited by random telephone digit dialing in France, Germany, Hungary, Italy, Spain, UK, Brazil and Mexico.Main outcome measuresTelephone interview checklist of 23 premenstrual symptoms, sociodemographic variables and lifestyle variables.ResultsThe most prevalent symptoms were abdominal bloating, cramps or abdominal pain, breast tenderness, irritability and mood swings. Severity of symptoms is directly proportional to duration ( R = 0.79). Hierarchical clustering found the following mental and physical domains and a typology: ‘Mild’ type (40.8%) with minimal symptoms; ‘Moderate M’ type (28.7%) with moderately severe, mostly mental symptoms; ‘Moderate P’ type (21.9%) with moderately severe, mostly physical symptoms; and ‘Severe’ type (8.6%) with severe intensity of both mental and physical symptoms. Multiple stepwise regression found significant effects on symptom duration severity index of age (linear and quadratic effects), current smoking and country.ConclusionsFurther research is needed on the impact of premenstrual symptoms on quality of life, and whether a brief symptom list could be developed as a valid and reliable tool globally.

Introduction Insufficient documentation exists regarding the prevalence of hypoactive sexual desire disorder (HSDD) in surgically menopausal (SM) women in European countries. Women who have undergone hysterectomy and bilateral oophorectomy experience a loss of ovarian hormones. Inclusion of these women in an epidemiological study provided the opportunity to study biological and cultural impacts on sexual function. Aim The aim of this study was to compare the prevalence of HSDD among SM women in France, Germany, Italy, and the United Kingdom, as well as the relationship between low sexual desire and sexual activity or behavior, and sexual or partner relationship satisfaction. Methods Cross-sectional survey of a convenience sample of 427 SM women aged 20–70 years. Main Outcome Measures The desire domain of the Profile of Female Sexual Function (PFSF) to identify women with low sexual desire, Personal Distress Scale (PDS) to measure distress caused by low sexual desire, and a sexual activities measure. Women with low sexual desire who were distressed were classified as having HSDD. Results SM women having low sexual desire ranged from 35% (United Kingdom) to 44% (Italy); of these women, 16% (Germany) to 56% (France) were distressed because of their low sexual desire. Overall, SM women classified with HSDD ranged from 7% (Germany) to 22% (France). A strong positive correlation was observed between sexual desire and arousal, orgasm, and sexual pleasure in all countries ( P Conclusions A similar percentage of SM women with low sexual desire were found across countries suggesting the role of biological factors (i.e., losing ovarian hormones) in determining sexual desire. Differences in the percentage of SM women with HSDD suggest a role for cultural factors in determining how low sexual desire is perceived. Graziottin A, Koochaki PE, Rodenberg CA, and Dennerstein L. The prevalence of hypoactive sexual desire disorder in surgically menopausal women: An epidemiological study of women in four European countries. J Sex Med 2009;6:2143–2153.

Introduction Previous, population‐based studies investigating the risk factors for sexual distress have not drawn on longitudinal data. Aims Determine the prevalence of sexual distress and dysfunction, explore factors associated with/predictive of sexual distress, and describe changes in sexual function over a decade in a population‐based sample of mid‐aged women. Methods Eleven‐year prospective study of Australian‐born women, aged 45–55 years, and menstruating at baseline. Short Personal Experiences Questionnaire (SPEQ) was completed in years 1 to 8 and 11 of follow‐up. Female Sexual Distress Scale (FSDS) was completed in the 11th year of follow‐up. Main Outcome Measures Validated outcome measures were the SPEQ (total sex score ≤7 indicates low sexual function) and FSDS (score ≥15 indicates sexual distress). Results Two hundred fifty‐seven women were interviewed in the 11th year of follow‐up. All domains of sexual function declined significantly in the decade studied. Women using hormone therapy in year 11 had significantly greater responsivity and higher frequency of sexual activities than nonusers. Two hundred four women completed both the FSDS and SPEQ questionnaires. One hundred sixty‐six (81%) women had an SPEQ score ≤7 of whom 34 (17% of the total sample) had an FSDS score ≥15, and were classified as having female sexual dysfunction. The multiple logistic regression analysis found that female sexual distress was concurrently associated with higher depression scores (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.10, 1.56) and more negative feelings for partner (OR 0.49, 95% CI 0.32, 0.76) and predicted by prior negative feelings for partner (OR 0.31, 95% CI 0.14, 0.70), and a greater decline in total sex score (OR 0.77, 95% CI 0.59, 0.99). Conclusion By the end of the sixth decade, women have low levels of sexual function. Hormone therapy may help these women maintain sexual function. A minority of these mostly postmenopausal women are significantly distressed about low sexual function. Sexual distress is associated with depression and relationship factors. Dennerstein L, Guthrie JR, Hayes RD, DeRogatis LR, and Lehert P. Sexual function, dysfunction, and sexual distress in a prospective, population‐based sample of mid‐aged, Australian‐born women. J Sex Med 2008;5:2291–2299.

Objective To investigate associations between the prevalence of sexual difficulties reported in published studies and design features of those studies to determine if differences in design contribute to variation in prevalence estimates. Design Systematic review, multivariate analysis. Setting Studies published internationally in English. Patient(s) Not applicable. Intervention(s) None. Main Outcome Measure(s) Prevalence estimates of difficulty with desire, arousal, orgasm, and sexual pain reported in published studies. Result(s) Our systematic literature search identified 1,380 publications. Fifty-five studies met our inclusion criteria (reporting prevalence, sample size and response rate, sample size greater than 100, not clinic based). Reported prevalence of sexual difficulty varied across studies (up to tenfold). Eleven aspects of research conduct in these studies were included in our multivariate analysis as explanatory variables. Five aspects of study design and conduct (data collection procedures, inclusion criteria, duration of sexual difficulty recorded, sample size, and response rate) were associated with the reported prevalence of at least one type of sexual difficulty independently of likely predictors of true variation in prevalence: study location, study year, and age range of participants. Conclusion(s) This review provides evidence that study design may influence reported prevalence estimates of female sexual difficulties and contribute to the wide variation in published estimates.

The menopausal transition is the stage in reproductive life commonly defined as commencing with the onset of menstrual irregularity. Classic studies of the endocrinology of the transition postulated the existence of inhibin in women to explain the observed increase in follicle-stimulating hormone (FSH) levels without a significant decrease in estradiol (E2). Descriptions were provided of cycle characteristics during the transition, emphasizing the unpredictability of the endocrine changes rather than the occurrence of an orderly and progressive decline in ovarian function. Women older than the age of 45 exhibited menstrual irregularity when the average number of primordial follicles per ovary decreased to approximately 100. Inhibin B is a major regulator of FSH secretion and a product of small antral follicles. Its levels respond to the early follicular phase increase and decrease in FSH. The age-related decrease in ovarian primordial follicle numbers, which is reflected in a decrease in the numbers of small antral follicles, leads to a decrease in inhibin B, which in turn leads to an increase in FSH, hypothesized to act as a stimulus to the maintenance of circulating E2 in the follicular phase until late in the transition. Concurrently, the concentrations of testosterone do not change significantly. Early follicular phase FSH levels in women reporting menstrual irregularity fluctuate markedly, with a more uniform increase in levels when no menses have occurred for at least 3 months. Anovulatory cycles occur at increased frequency in the last 30 months before final menses or menopause. In ovulatory cycles, FSH shows little, if any, increase, but anovulatory cycles are usually characterized by low levels of inhibin B, markedly increased levels of FSH, and low levels of E2. Thus, the heterogeneity of follicular phase FSH represents a mixture of ovulatory and anovulatory cycles. Longitudinal data indicate that both ovulatory and anovulatory cycles occur after entry into both the early and late menopausal transition and that ovulatory cycles occur even after final menses. There is no endocrine marker of menopause, which may be primarily an endometrial event. Using the hormonal concentrations in ovulatory cycles observed in women in mid-reproductive age as controls and comparing such concentrations in late reproductive age women older than 45 either continuing to cycle regularly or having entered the early or late menopausal transition, a gradual increase in follicular phase FSH and E2 and a decrease in inhibin B were observed in ovulatory cycles. Anovulatory cycles showed markedly increased FSH with low E2 and inhibin B. No specific endocrine change was characteristic of either the early or late menopausal transition, confirming the observations of previous studies regarding the unpredictability of cycle characteristics and hormone changes with the approach of menopause. Antimullerian hormone correlates with follicle numbers and shows a large age-related decrease to reach undetectable levels at menopause. Thus, the marked decrease in follicle numbers during late reproductive age appears to predispose to erratic and unpredictable cycle characteristics, with normal ovulatory cycles continuing to occur episodically. There is no specific endocrine marker of the early or late transition, making measurements of FSH or E2 unreliable in attempting to stage an individual with regard to approaching menopause.

Introduction No previous population-based studies have used validated instruments to measure female sexual dysfunction (FSD) in Australian women across a broad age range. Aim To estimate prevalence and explore factors associated with the components of FSD. Main Outcome Measures Sexual Function Questionnaire measured low sexual function. Female Sexual Distress Scale measured sexual distress. Methods Multivariate analysis of postal survey data from a random sample of 356 women aged 20–70 years. Results Low desire was more likely to occur in women in relationships for 20–29 years (odds ratio 3.7, 95% confidence intervals 1.1–12.8) and less likely in women reporting greater satisfaction with their partner as a lover (0.3, 0.1–0.9) or who placed greater importance on sex (0.1, 0.03–0.3). Low genital arousal was more likely among women who were perimenopausal (4.4, 1.2–15.7), postmenopausal (5.3, 1.6–17.7), or depressed (2.5, 1.1–5.3), and was less likely in women taking hormone therapy (0.2, 0.04–0.7), more educated (0.5, 0.3–0.96), in their 30s (0.2, 0.1–0.7) or 40s (0.2, 0.1–0.7), or placed greater importance on sex (0.2, 0.05–0.5). Low orgasmic function was less likely in women who were in their 30s (0.3, 0.1–0.8) or who placed greater importance on sex (0.3, 0.1–0.7). Sexual distress was positively associated with depression (3.1, 1.2–7.8) and was inversely associated with better communication of sexual needs (0.2, 0.05–0.5). Results were adjusted for other covariates including age, psychological, socioeconomic, physiological, and relationship factors. Conclusions Relationship factors were more important to low desire than age or menopause, whereas physiological and psychological factors were more important to low genital arousal and low orgasmic function than relationship factors. Sexual distress was associated with both psychological and relationship factors. Hayes RD, Dennerstein L, Bennett CM, Sidat M, Gurrin LC, and Fairley CK. Risk factors for female sexual dysfunction in the general population: Exploring factors associated with low sexual function and sexual distress.

Summary Objective To determine the question that best predicts radiographic evidence of non-axial osteoarthritis (OA). Design The Melbourne Women's Mid-life Health Project (MWMHP), commenced in 1991, is a population-based prospective study of 438 Australian-born. Two hundred and fifty-seven (57%) women remained in longitudinal assessment in 2002 and 224 (87%) women agreed to undergo X-rays of their hands and knees between 2002 and 2003. Methods Annually participants were asked about aches and stiff joints and arthritis or rheumatism. In the eleventh year of follow-up X-rays were scored for evidence of OA using a validated scale, by two investigators who were blinded to questionnaire results. Information on hormone therapy use, physical activity, mood, smoking, body mass index (BMI) and age were obtained by both self-administered and face-to-face questionnaires. Results Patient reported physician diagnosed arthritis was the best predictor of radiological OA (ROA). The question had a specificity of 64%, a positive predictive value of 57% and a negative predictive value of 71%. Even the most reliable question about arthritis still had a relatively low specificity for radiologically diagnosed OA. Reporting symptoms were significantly more common in participants who were depressed, those who had a higher negative affect and those with a higher BMI. Conclusion In large epidemiological studies where questionnaire assessment of OA is required, the greatest accuracy is achieved by asking about physician diagnosed arthritis. Concurrent application of a validated scale for mood is important.

Introduction A range of methodological inconsistencies has the potential to affect reported prevalence rates of sexual intercourse. Aims We reviewed published studies of sexual intercourse frequency reported by women and associated factors. Methods Literature search of electronic databases. Inclusion criteria for selected cross-sectional studies were population and community-based studies of frequency of intercourse in women published in English or German languages with sample size greater than 300. Longitudinal studies were selected if duration was at least 1 year and samples were not clinically based. Main Outcome Measures Frequency of sexual intercourse/activities and any associated factors. Results There was a great deal of variation in the mean frequency of intercourse across all age groups with higher rates reported by European and American women. There was a reduction in frequency of sexual intercourse from age 50 among women from Europe and the United States. Asian women reported increasing rates through the age group 20–30 followed by a decline. Change with age was not as evident among African and South American studies. Factors most often associated with the frequency of sexual intercourse were age, parity, duration of relationship, pregnancy, time, relationship status, fertility intentions, and contraception. Conclusions There is variation in reported frequency of sexual intercourse between studies, age groups, and continents. Some of the variation may be due to variation in definitions, study designs, and methods suggesting a need for greater consistency in research practice. Schneidewind-Skibbe A, Hayes RD, Koochaki PE, Meyer J, and Dennerstein L. The frequency of sexual intercourse reported by women: A review of community-based studies and factors limiting their conclusions.

OBJECTIVES Part I: To determine factors associated with reported joint symptoms across the menopausal transition. Part II: To investigate the relationship between symptom reporting and radiological arthritis in postmenopausal women. DESIGN Part I: The Melbourne Women's Mid-life Health Project, commenced in 1991, is a population-based prospective study of 438 Australian-born women, aged 45-55 years and menstruating at baseline; they were interviewed annually over 8 years. The retention rate was 88% (n = 387). Part II: After 12 years of follow-up, 257 (57%) women returned for assessment and 224 agreed to undergo X-rays of their hands and knees. METHODS Part I: Annual fasting blood collection, physical measurements, and interviews including questions about bothersome aches or stiff joints in the previous 2 weeks. A score for this symptom was calculated from the product of the severity and frequency data. These data were analyzed using random-effects time-series regression models. Part II: X-rays were scored for evidence of osteoarthritis using a validated scale, by two investigators who were blinded to questionnaire results. RESULTS Part I: 'Aches and stiff joints' were the most commonly reported symptom and reporting increased over time in the longitudinal study. Variables significantly associated with reporting bothersome aches and stiff joints were high body mass index (BMI) (p0.001), high negative mood (p0.01), not being employed (p0.001), and experiencing the menopausal transition (p0.05). A higher severity and frequency of this symptom were associated with BMI (p0.01), not being employed (p0.05) and high negative mood (p0.005). Part II: The relationship between radiological osteoarthritis and symptom reports approached statistical significance (p = 0.06). Knee osteoarthritis was significantly associated with symptom reports (p = 0.008) but not hand osteoarthritis (p = 0.2).Menopausal status, BMI, employment status and depressed mood were all associated with the experience of bothersome aches and stiff joints. Aches and stiff joints, common in postmenopausal women, are not necessarily indicative of radiological osteoarthritis.

To examine whether physical-activity patterns over a period of 4 years are associated with well-being.A sample of 399 women aged 50-60 years participated in the study. Measures included rate of physical activity and other life style behaviors, well-being, health status, and interpersonal stress. Sufficient and insufficient exercisers were identified, and the association of this dichotomy with well-being, along with the contribution of the other variables, was examined.The distribution of physical-activity patterns remained stable over the 4 years of the study, with 40% of the women exercising leisurely and 15-20% exercising vigorously four to seven times a week. Approximately 50% of the women were considered sufficiently active in terms of public recommendations. Random effects regression analysis revealed that sufficient exercise along with a low frequency of daily hassles, relatively few menopausal symptoms, and a low level of interpersonal stress significantly contributed to the variability of well-being.These data evoke the need for a better understanding of exercise behavior and its promising potential contribution to the well-being of middle-aged women.

This article aims to educate the nonpsychiatric as well as the psychiatric clinician on the impact of vasomotor symptoms in women with comorbid psychiatric problems and the challenges of treating vasomotor symptoms in these women. The pathophysiology, prevalence and common risk factors associated with disturbing hot flashes in the menopausal transition are reviewed. Hormonal, nonhormonal and behavioral treatment options of vasomotor symptoms for these women are discussed. Special pharmacokinetic implications for hormonal treatment of those women on anticonvulsant medications for the treatment of their mood disorders, on tamoxifen and/or with high or low sex hormone-binding globulin are examined. An in-depth discussion of mood and the menopausal transition, theoretical mechanisms for mood problems with the symptomatic menopause and the impact of stress on the symptomatic menopause are found elsewhere in this clinical review series on psychiatric illness, stress and the symptomatic menopause.

Studies and treatments for the symptomatic menopausal woman with sleep complaints have been reviewed elsewhere. This article, as part of the clinical review series on the comorbid symptomatic menopausal woman, aims to examine the evidence for diagnosis and treatment of women who present with distressing sleep symptoms that they attribute to menopause. The etiology of these symptoms may be a psychiatric disorder, a pre- or co-existing problem with sleep, or a dynamic interaction among one of these and/or a symptomatic menopause. The relationship between sleep disturbance and cognitive complaints, mood problems, fatigue and low energy will be reviewed. The new research on sleep, clinical consequences of insomnia of various types, the impact of sleep disturbance on morbidity and functioning – in the context of the midlife woman in the menopausal transition – will be explored along with the evidence for different treatment strategies for these sleep problems.

Women experience a high prevalence of mood and anxiety disorders, and comorbidity of mood and anxiety disorders is highly prevalent. Both mood and anxiety disorders disturb sleep, attention and, thereby, cognitive function. They result in a variety of somatic complaints. The mood disorder continuum includes minor depression, dysthymia, major depression and bipolar disorder. Chronobiological disorders, such as seasonal affective disorder as well as premenstrual dysphoric disorder, occur in some women, with comorbid seasonal affective disorder and premenstrual dysphoric disorder in just under half of these individuals [1] . Early life experience, heritability, gender, other psychiatric illness, stress and trauma all interact dynamically in the development of mood and anxiety disorders. The epidemiology, nomenclature and clinical diagnostic issues of these illnesses in midlife woman are reviewed.

Somatic symptoms characterized by arthralgias, bodily aches and pains, musculoskeletal pain and joint pain have been investigated in a number of menopause and depression studies. Although depression is one of the most common causes of bodily aches and pains, and arthralgias, these same symptoms are also commonly associated with a natural menopause, surgical menopause and menopause induced by chemotherapy in breast cancer treatment. Somatic symptoms in the absence of definitive medical diagnoses result in these patients receiving various diagnoses and labels--'medically unexplained symptoms', 'worried well', as well as various Diagnostic and Statistical Manual of Mental Disorders (4th edition) somatoform diagnoses. Osteoarthritis and joint pain increase in prevalence from premenopausal- to menopausal-aged women with hormonal change implicated in their etiology. The current research on the relationships among menopause, depression, nociceptive mechanisms, perception and pain in the distressed midlife patient is discussed. The amelioration and management of pain symptoms in the menopausal and postmenopausal woman, with or without comorbid depression, have been elusive and difficult problems for clinicians. Familiarity with the differential diagnosis, pathophysiology and evidence-based treatment for such patients is crucial to their proper care.

Culture, individual health beliefs and distressing symptoms frequently determine women's perceptions of their menopausal transitions. Women's perceptions of mental health problems and the acceptability of different interventions greatly affect if and what a woman is willing to try as a treatment option and whether or not she will accept the possibility that her menopausal symptoms represent a comorbidity with a diagnosis, such as depression or anxiety. These perceptions have a significant impact on women's choices with regard to health practices, as well as on whether or not they will seek out medical care for their distressing symptom(s). Working with a woman's beliefs, sharing decision making, and empowering her through health education are all critical aspects of the treatment of the patient with comorbid perimenopausal symptoms, regardless of their etiology.

Stress plays an essential role in the development, continuation and exacerbation of mood problems throughout a woman's life. It exacerbates somatic symptoms of menopause, increasing the risk of recurrence of mood disorders, as well as of a mood disorder de novo throughout the lifespan and specifically in the menopausal transition. Chronic stress affects the hypothalamic-pituitary axis, hypothalamic-pituitary-ovarian axis, the proinflammatory cytokines and cardiovascular risk. The current evidence for the potential interactions between acute stress, chronic stress, childhood stress and victimization, and individual susceptibility to the development of depression and/or anxiety in response to stressful life events, are reviewed in the context of the increasing data on the association of these and a symptomatic menopausal transition. Strategies for the optimal approach for clinicians to evaluate and treat the symptomatic perimenopausal patient with stressful life events and comorbid mood disorders are presented.

The menopause, defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity, marks the end of natural female reproductive life. It is preceded by a period of menstrual cycle irregularity, the menopausal transition, which usually begins in the mid-40s and is conventionally divided into early and late phases. The endocrine changes, which underlie the transition, are predominantly the consequence of a marked decline in ovarian follicle numbers. The most significant changes include a decrease in early cycle inhibin B and in anti-Mullerian hormone (AMH) levels. The decline in inhibin B results in an increase in FSH, which appears to be an important factor in the maintenance of estradiol (E2) concentrations until late in reproductive life. In the post-menopause, FSH levels are markedly raised, E2 levels are low, whereas inhibin B and AMH are undetectable. The menopausal transition is a time of marked hormonal instability. The Melbourne Women's Midlife Health Project has been an extremely productive study in which it has been possible to describe longitudinal changes in hormone levels throughout the menopause transition and to separate the effects of hormone change from the effects of ageing on a number of endpoints. This review provides the background for an accompanying manuscript in which a novel approach to modelling the hormonal changes during the transition is described.

Changes in FSH and estradiol (E2) across the menopausal transition are clearly not linear. The present study utilizes data from 204 women who completed the 13-year prospective Melbourne Women's Midlife Health Project. E2, FSH, symptoms, self-rated health, mood, sexual function and coronary heart disease (CHD) risk were measured longitudinally. We presumed an s-shaped curve for each hormone and estimated five parameters for each hormone curve for each woman: baseline, final value, range, slope at inflexion point and age at inflexion point. These parameters were found to adequately estimate the curve for each hormone. The median age of transition observed for E2 occurs >1 year later than the median age of transition observed for FSH. FSH parameters did not affect any of the health outcomes analysed. Hot flushes, night sweats, sleeping problems, vaginal dryness and to a lesser extent self-rated health were highly significantly associated with E2 range and slope. Sexual response and CHD risk were highly significantly associated with final E2 level (post-menopausally). These findings have clinical relevance in identifying which symptoms will be triggered by steep transitions of E2 such as sudden withdrawal and which health parameters may require a maintenance level of E2.