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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Objective: The aim of this review was to summarize the literature regarding the impact of the menopause transition on body weight and body composition., Methods: We conducted a search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2012) for English-language studies that included the following search terms: 'menopause', 'midlife', 'hormone therapy' or 'estrogen' combined with 'obesity', 'body weight' or 'body composition'., Results: Whereas weight gain per se cannot be attributed to the menopause transition, the change in the hormonal milieu at menopause is associated with an increase in total body fat and an increase in abdominal fat. Weight excess at midlife is not only associated with a heightened risk of cardiovascular and metabolic disease, but also impacts adversely on health-related quality of life and sexual function. Animal and human studies indicate that this tendency towards central abdominal fat accumulation is ameliorated by estrogen therapy. Studies mostly indicate a reduction in overall fat mass with estrogen and estrogen-progestin therapy, improved insulin sensitivity and a lower rate of development of type 2 diabetes., Conclusion: The hormonal changes across the perimenopause substantially contribute to increased abdominal obesity which leads to additional physical and psychological morbidity. There is strong evidence that estrogen therapy may partly prevent this menopause-related change in body composition and the associated metabolic sequelae. However, further studies are required to identify the women most likely to gain metabolic benefit from menopausal hormone therapy in order to develop evidence-based clinical recommendations.

The prevalence of major depression disorder in women is double that seen in men, with the menopause transition being associated with increased vulnerability to depression. Selective serotonin reuptake inhibitors (SSRIs), which constitute 70-80% of antidepressant prescriptions, are associated with secondary sexual dysfunction in 35-70% of users. Different strategies for approaching sexual dysfunction secondary to SSRI medication have been investigated. Most interventions fail to show significant benefit on sexual function compared to placebo; moreover, adjuvant therapies commonly result in side-effects and tolerability problems. While antidepressant-associated sexual dysfunction in women has been a concern for many years, there remains a need for more research into the optimal management of antidepressant-associated sexual dysfunction in women, including multidisciplinary approaches. Further randomized, controlled trials assessing multidisciplinary approaches are required before clinicians or patients can be confident of the benefits of any intervention. Despite the efficacy of testosterone in improving sexual function in non-depressed women, there is no information regarding the efficacy of testosterone in treating antidepressant-associated sexual dysfunction in women.

Background: The loss of estrogen at menopause and the gradual decline in testosterone with age are associated with urogenital atrophy and, as a result, urogenital tract symptoms, including lower urinary tract symptoms and dyspareunia. These symptoms will persist unless treated., Objective: To review the prevalence of urogenital tract symptoms and sexual health problems associated with menopause and the role in the use of hormone therapy for the treatment of symptomatic women, with a specific focus on what has been learned since the first publication of the Women's Health Initiative (WHI) estrogen and estrogen + progestin studies., Conclusion: Studies support the use of local estrogen therapy, but not systemic estrogen therapy, for the treatment of urge urinary incontinence, overactive bladder and to reduce the number of urinary tract infections. The current evidence does not favor a beneficial effect on stress urinary incontinence. Local estrogen therapy is effective for the treatment of dyspareunia caused by vulvovaginal atrophy. Preliminary studies suggest a potential role for both intravaginal dehydroepiandrosterone and testosterone in the treatment of dyspareunia secondary to vulvovaginal atrophy, however, confirmatory studies are required before either therapy can be recommended. Post WHI, there is a need for medical practitioners to proactively raise the topic of urogynecological and sexual health in order to discuss the most suitable treatment option.

Background: Cosmetic breast surgery is amongst the top five most commonly performed cosmetic surgical procedures. With breast cancer being the most common non-skin malignancy in women, the likelihood that a woman undergoing cosmetic breast surgery may have an occult breast cancer needs to be considered. Most of the available data pertaining to breast cancer diagnosis in the setting of cosmetic surgery are from studies of cosmetic breast surgery populations. We report on the prevalence of breast cancer as an incidental finding during cosmetic breast surgery in the context of women subsequently diagnosed with invasive breast cancer., Methods: The Bupa Health Foundation Health and Wellbeing after Breast Cancer Study is a prospective cohort study of 1684 women recruited within 12 months of their first diagnosis with invasive breast cancer. Participants completed an enrolment questionnaire and annual follow-up questionnaires for 5 years., Results: At the second follow-up, 1.5% of women reported having undergone cosmetic breast surgery prior to being diagnosed with breast cancer, 16 had undergone breast reduction and seven had augmentations. Invasive breast cancer was diagnosed at the time of a cosmetic breast procedure in two women, in both an augmentation and a reduction procedure, which is 8.7% (95% confidence interval 23.5% to +20.9%) of the women in our study reporting a cosmetic breast procedure prior to diagnosis., Conclusions: Although prior cosmetic breast surgery was reported by few women, breast cancer was diagnosed in two women during the procedure. Surgeons performing elective breast surgery need to understand and apply consistent, reliable breast cancer screening practices.

Objective: To evaluate the efficacy and safety of a transdermal testosterone patch (TTP, 300 microg/day) in naturally menopausal women with hypoactive sexual desire disorder (HSDD)., Methods: A total of 272 naturally menopausal women, predominantly not using hormone therapy, were randomized in this 6-month, placebo-controlled, double-blind, multicenter study to receive twice weekly either TTP or an identical placebo. Efficacy endpoints measured were the 4-week frequency of satisfying sexual episodes (SSE) using the Sexual Activity Log, the sexual desire domain of the Profile of Female Sexual Function and distress by the Personal Distress Scale. Safety was assessed by adverse events, laboratory parameters and hormone levels., Results: The TTP group demonstrated significant improvements in SSE (p = 0.0089) as well as in sexual desire (p = 0.0007) and reduced personal distress (p = 0.0024) versus placebo at 6 months (intent-to-treat analysis, n = 247). The results were significant for all three endpoints in the subgroup (n = 199) not using hormone therapy. Similar numbers of women treated with placebo and TTP discontinued (n = 39, 27.5% vs. n = 26, 20%), reported adverse events (including application site reactions) (n = 101, 71.1% vs. n = 81, 62.3%) and withdrew due to adverse events (n = 20, 14.1% vs. n = 9, 6.9%). No clinically relevant changes were noted in laboratory parameters. Serum free and total testosterone levels increased from baseline in the TTP group (geometric means 5.65 pg/ml and 67.8 ng/dl, respectively, at week 24) within the physiological range; no changes were seen in estradiol and sex hormone binding globulin levels., Conclusions: TTP was effective in treating HSDD and improving sexual function in this study of naturally menopausal women with and without concurrent hormone therapy.

Objectives: To examine the relationships between well-being and different levels of both low back pain intensity and disability in women living in the community., Methods: A detailed, self-administered questionnaire was mailed to 542 community-dwelling women, aged 24-80 years. Participants provided demographic data and completed the Chronic Pain Grade Questionnaire and Psychological General Well-being Index (PGWB)., Results: A total of 506 participants (93.4%) returned completed questionnaires. Multivariate analysis revealed associations between lower total PGWB scores and both low (odds ratio (OR) -5.53; 95% confidence interval (CI) -9.01, -2.06) and high pain intensity (OR -8.36; 95% CI -13.8, -2.92) compared with no pain intensity, after adjusting for confounders. Lower total scores on the PGWB were also associated with low (OR -4.72; 95% CI -9.04, -0.41) and high disability (OR -9.26; 95% CI -15.2, -3.30), compared with no disability. There were also statistically significant associations between lower scores on the PGWB subdomains and low and high pain intensities, and low and high disabilities., Conclusions: We found that it is not only women with high pain intensity and disability who experience reduced well-being, but also those with low levels of pain and disability. Longitudinal investigation is needed to investigate the predictive nature of both low and high levels of pain and disability in determining poor well-being in community-based women.

Background: Factors that contribute to cognitive decline in women from midlife remain poorly understood. There are circumstantial data indicating a positive association between homocysteine and cognitive decline and that endogenous and exogenous estrogen may influence homocysteine levels. The aim of this review was to establish what is known of the relationships between cognitive change and homocysteine levels, and the impact of the menopause transition and exogenous estrogen on homocysteine levels., Methods: We reviewed the recent published literature from 1993 to 2005 pertaining to the current understanding of the relationship(s) between plasma homocysteine levels and cognitive functioning and endogenous hormone levels and exogenous estrogen use in women., Results: Hyperhomocysteinemia is consistently associated with cognitive decline. Dietary supplementation with vitamins may assist in normalizing homocysteine levels; however, there is no evidence that this results in favorable effects on cognition. Changes in endogenous estrogen levels are inversely associated with changes in serum homocysteine. Consistent with this, estrogen therapy is associated with reductions in plasma homocysteine, with the greatest effects reported in women with higher levels of homocysteine at baseline. Limited data indicate that tibolone is associated with little change in homocysteine. The use of raloxifene, the most studied selective estrogen receptor modulator, is associated with a modest reduction in homocysteine., Conclusions: There are data to suggest an underlying link between homocysteine levels and cognitive decline. There is also evidence for a link between both the menopause transition and use of exogenous estrogen therapy and homocysteine levels. Clinical data do not support a role for exogenous estrogen in the prevention of dementia in older women; however, the 'window of opportunity' theory suggests that there is a need for randomized controlled trials to evaluate the role of estrogen in the early postmenopausal years to protect against cognitive decline in later life.

Objective: Knee cartilage volume measurement requires significant time and training. Simplifying the measurement may improve feasibility. We investigated whether the area of cartilage shown on the middle slice of the medial and lateral tibial cartilages on sagittal MRI correlates with radiological features of osteoarthritis (OA), cartilage volume, and longitudinal change in cartilage volume., Methods: One hundred and seventy-three subjects (normal and osteoarthritic), who had serial magnetic resonance imaging (cartilage volume measured) and baseline weight-bearing antero-posterior radiographs of the same knee were examined., Results: In the lateral compartment, with increasing grade of OA there was a significant reduction in cartilage area. In the medial compartment, this was true for medial joint-space narrowing (after adjusting for gender). There was a moderate to strong association between cartilage area and volume, especially in those with early or no OA. However, when change over time was examined, the strength of these relationships was weak., Conclusion: Our data suggests that cartilage area may provide a simple surrogate measure of cartilage volume, in cross-sectional studies, after adjustment for gender: especially in subjects with early disease. However, before it can be widely used, further investigation will be required.

Objective: To compare the effects of transferring from low-dose transdermal estrogen to raloxifene (RLX), with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, on serum lipids and fibrinogen in postmenopausal women previously administered estrogen plus progestogen therapy., Methods: Sixty postmenopausal women (mean age 55 years) were randomized to one of two treatment groups: RLX + low-dose transdermal estrogen (RLX + E) or RLX + placebo. The study consisted of four 8-week phases: phase I (all subjects low-dose transdermal estrogen 25 microg/day), phase II (double-blind RLX 60 mg every 2nd day in combination with either low-dose transdermal estrogen or placebo), phase III (all subjects RLX 60 mg every 2nd day + placebo) and phase IV (all subjects RLX 60 mg/day + placebo)., Results: No significant differences existed between groups for baseline measurements prior to phase I. In phase I, for all subjects combined, total cholesterol and low-density lipoprotein cholesterol both showed a significant increase (median increase of 0.2 mmol/l, p = 0.008 and 0.4 mmol/l, p< 0.001, respectively), while triglycerides decreased significantly (median decrease of 0.2 mmol/l, p< 0.001). For the primary analysis (phase II to phase IV), the mean change from baseline observations showed no significant differences between the therapy groups for serum lipids, fibrinogen, vital signs or weight. In the comparison phase (phase II), changes in serum lipids, fibrinogen, vital signs and weight were not significantly different between groups., Conclusion: Gradual conversion to RLX from low-dose transdermal estrogen, with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, does not have any effect on the serum lipid profile or fibrinogen level.

We aimed to estimate the likely prevalence of polycystic ovary syndrome (PCOS) in indigenous Australian women in a cross-sectional survey based on structured interviews. In the Kimberley region of Western Australia and south-western Victoria, between February and June 1999, women over the age of 18 available for interview and willing to participate were included. Menstrual status, anthropometric measures, fasting blood biochemistry and hirsutism were assessed. A total of 38 premenopausal women completed the survey. Of these, 50% had regular menstrual cycles of normal duration and no hirsutism; seven had oligomenorrhea and hirsutism/hyperandrogenemia; and of the nine women with hirsutism and regular menses, three had hyperandrogenemia. Thus, possibly ten women fulfilled the criteria of PCOS. This unique data set suggests a high prevalence of PCOS in indigenous Australian women. Further research to document this formally is warranted, in view of the potential adverse effects of PCOS on reproduction and metabolism.

Background: Most studies examining the potential cardioprotective effects of postmenopausal estrogen have been undertaken in healthy women, with doses that may not be appropriate for long-term intervention. New low-dose estrogen-progestin regimens alleviate postmenopausal symptoms with a favorable side-effect profile; however, little is known of the impact of such regimens in women at increased risk of cardiovascular disease. Hence, we have evaluated the effects of low-dose oral estrogen-progestin therapy on serum lipoprotein lipids, brachial artery reactivity and fibrinogen in hypercholesterolemic postmenopausal women in direct comparison with the effects of pravastatin, a lipid-lowering agent known to reduce cardiovascular events in women., Methods: In a randomized, double-blind, double-dummy, parallel trial, we studied the effects of continuous combined estrogen-progestin therapy (1 mg 17beta-estradiol with 500 micro g norethisterone acetate daily) or pravastatin (20 mg daily) in 72 postmenopausal women with fasting serum low-density lipoprotein (LDL) cholesterol levels greater than 124 mg/dl after an 8-week run-in diet, over a 24-week period. The primary end-point was percentage change in LDL cholesterol from baseline., Results: The intention-to-treat population comprised 65 women, mean age 59 +/- 6.3 years, and 29 in each group completed the trial. Diet alone reduced LDL cholesterol significantly in both treatment groups, in association with a reduction in weight during this period. Compared with respective baseline values, pravastatin decreased LDL cholesterol and total cholesterol to a greater extent than hormone therapy (p = 0.0001 and 0.003 for difference between treatments, respectively). High-density lipoprotein (HDL) cholesterol levels decreased with hormone therapy, but did not change with pravastatin (p = 0.01). Lipoprotein(a) decreased significantly with hormone therapy only (-14%, 95% confidence interval (CI) -21 to -6%, p = 0.01 for difference between groups). Brachial artery flow-mediated dilatation (FMD) was impaired at baseline, and this increased with hormone therapy (absolute mean change in artery diameter as percentage units 2.07, 95% CI 0.57-3.57, p = 0.009) versus no change with pravastatin (0.19, 95% CI -1.1 to 1.5, p = 0.78), with a near-significant difference between the two groups (p = 0.058). A significant correlation between improved brachial artery FMD and reduction in LDL cholesterol was not observed. Fibrinogen decreased significantly in both treatment groups with no difference between treatments., Conclusions: In postmenopausal hypercholesterolemic women, pravastatin and hormone therapy exhibited divergent effects. The former lowered total and LDL cholesterol more effectively, whereas hormone therapy lowered lipoprotein(a) significantly and improved brachial artery endothelium-dependent dilatation, independent of the reduction in LDL cholesterol. The modest increase in brachial artery FMD seen is consistent with hypercholesterolemia compromising endothelial integrity, and suggests that the important effect of estrogen on the endothelial microenvironment may be attenuated in women with endothelial dysfunction.

Objective: Substantial improvements in lipoprotein-lipid profiles have previously been shown with both simvastatin and combined estrogen-progestin therapy in postmenopausal hypercholesterolemic women. Since little is known about the impact of the concomitant use of these therapies, the effects of concurrent hormone therapy and simvastatin in hypercholesterolemic postmenopausal women have been evaluated., Methods: Twenty-three postmenopausal women with fasting serum total cholesterol levels greater than 250 mg/dl received, in a randomized cross-over design, simvastatin (10 mg daily) for 8 weeks or postmenopausal hormone therapy (up to 1.25 mg of conjugated equine estrogens plus 5 mg of medroxyprogesterone acetate daily) for 8 weeks, with an 8-week wash-out interval between the two treatment periods. In a third, non-randomized treatment period after a second wash-out interval, each woman received a combination of simvastatin and postmenopausal hormone therapy in the same dosage regimens as above. Fasting blood was sampled monthly from baseline to measure total cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, triglycerides and lipoprotein(a)., Results: For total cholesterol, the mean decreases with hormone therapy, simvastatin and combination therapy were 12% (95% confidence interval 6-17%), 26% (20-31%) and 28% (24-31%), respectively, and for LDL cholesterol 21% (14-27%), 37% (30-44%) and 46% (41-51%), respectively. Simvastatin was more effective than hormone therapy (p < 0.001), while the effect of the combined therapy was even greater (total cholesterol, p = 0.012; LDL cholesterol, p < 0.001). The level of HDL cholesterol increased similarly with each treatment: 4% (-3-11%), 6% (2-10%) and 7% (2-13%), respectively. Triglyceride levels increased with hormone therapy and decreased with simvastatin (p < 0.001), while there was little change with the combination (effect of combined therapy vs. simvastatin, p = 0.002; vs. hormone therapy, p < 0.001). Both hormone therapy and combined therapy reduced lipoprotein(a) similarly (-23% and -14%, respectively, p = 0.078). Simvastatin had no effect on lipoprotein(a) levels., Conclusion: For postmenopausal women with hypercholesterolemia, use of a statin in combination with continuous combined oral estrogen and progestin therapy can result in a more cardioprotective lipoprotein-lipid profile than that achieved with either therapy used alone.

We have investigated the effect of hypophysectomy on adult rat ovarian inhibin alpha- and beta A-subunit mRNA, serum inhibin, and circulating gonadotrophin levels. Immediate declines in ovarian inhibin gene expression and serum inhibin were observed following hypophysectomy, with a nadir on day 4. However, inhibin synthesis determined by these parameters was still apparent at 16 days post-hypophysectomy. Gonadotropin levels were suppressed following hypophysectomy and the fall in inhibin production was highly correlated with disappearance of FSH from the circulation. This study demonstrates that removal of pituitary gonadotropin stimulation results in diminished ovarian inhibin synthesis and provides further evidence indicating that FSH stimulates granulosa cell inhibin synthesis by enhancing inhibin gene transcription.