Recommended measurement instruments for genitourinary symptoms associated with menopause: the COMMA (Core outcomes in menopause) consortium.

OBJECTIVE: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects. METHODS: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome. RESULTS: A total of 87 publications reporting on 34 PROMs were identified from 21,207 publications screened. Of these 34 PROMs, 29 were not considered to sufficiently map onto the core outcomes, and 26 of these also had insufficient measurement properties. Therefore, only five PROMs corresponding to two core outcomes were considered for recommendation. We recommend the PROMIS Scale v2.0 - Sexual Function and Satisfaction: Vaginal Discomfort with Sexual Activity to measure the outcome of "pain with sexual activity" and the Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire to measure "distress, bother or interference" from genitourinary symptoms. Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events in study participants, which is a requirement of Good Clinical Practice. CONCLUSIONS: Suitable PROMs and definitions were identified to measure three of eight core outcomes. Because of the lack of existing measures, which align with the core outcomes and have evidence of high-quality measurement properties, future work will focus on developing or validating PROMs for the remaining five core outcomes.

A systematic review and critical appraisal of menopause guidelines.

OBJECTIVE AND RATIONALE: To identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust examples. DESIGN: Systematic review. DATA SOURCES: Ovid MEDLINE, EMBASE, PsycINFO and Web of Science ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Practice guidance documents for menopause published from 2015 until 20 July 2023. Quality was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. RESULTS: Twenty-six guidance papers were identified. Of these, five clinical practice guidelines (CPGs) and one non-hormonal therapy position statement met AGREE II criteria of being at least of moderate quality. The five CPGs listed symptoms associated with the perimenopause and menopause to be vasomotor symptoms (VMS), disturbed sleep, musculoskeletal pain, decreased sexual function or desire, and mood disturbance (low mood, mood changes or depressive symptoms). Acknowledged potential long-term menopause consequences were urogenital atrophy, and increased risks of cardiovascular disease and osteoporosis. VMS and menopause-associated mood disturbance were the only consistent indications for systemic menopausal hormone therapy (MHT). Some CPGs supported MHT to prevent or treat osteoporosis, but specific guidance was lacking. None recommended MHT for cognitive symptoms or prevention of other chronic disease. Perimenopause-specific recommendations were scant. A neurokinin 3B antagonist, selective serotonin/norepinephrine (noradrenaline) reuptake inhibitors and gabapentin were recommended non-hormonal medications for VMS, and cognitive behavioural therapy and hypnosis were consistently considered as being of potential benefit. DISCUSSION: The highest quality CPGs consistently recommended MHT for VMS and menopause-associated mood disturbance, whereas clinical depression or cognitive symptoms, and cardiometabolic disease and dementia prevention were not treatment indications. Further research is needed to inform clinical recommendations for symptomatic perimenopausal women.

Genome-wide association study identifies genetic regulation of oestrone concentrations and association with endometrial cancer risk in postmenopausal women.

BACKGROUND: Oestrone, predominantly made in fat, is the main circulating oestrogen and important for target tissue oestradiol production in women after menopause. The present study was undertaken to determine the genetic regulation of blood oestrone, measured with precision, in postmenopausal women and to explore associations between the identified genetic loci and endometrial cancer in a large, independent cohort. METHODS: A genome-wide association study (GWAS) was undertaken in women aged at least 70 years to identify genetic associations with blood oestrone concentrations measured by liquid chromatography and tandem mass spectrometry. The GWAS included participants from the Sex Hormones in Older Women (SHOW) study, a sub-study of the longitudinal ASPREE (ASPirin in Reducing Events in the Elderly) randomised trial. Of the 6358 women providing a biobank sample at enrolment, 4951 unrelated women of European ancestry, not taking sex hormones, anti-oestrogens, anti-androgens or systemic glucocorticoids were included in the GWAS. Single nucleotide polymorphisms (SNPs) from loci identified below the genome-wide significance threshold were then tested in an independent cohort (the UK Biobank) for association with endometrial cancer risk, using logistic regression and adjusting for age, body mass index (BMI) and the top 10 genetic principal components. FINDINGS: The median age of the 4951 women included in the GWAS was 75.9 years (range 70-94.8 years). The GWAS identified four independent SNPs associated with oestrone concentrations (p < 5 × 10-8). Among them, the effect (minor) alleles rs34670419-T, rs2846729-T and rs2414098-T were associated with lower oestrone concentrations. Carrying these effect alleles was associated with lower oestrone concentrations in a dose-dependent manner. The effect allele rs56400819-A was associated with higher oestrone concentrations. When applied to UK Biobank, carrier status for rs2414098-T associated with the CYP19A1 gene which encodes the aromatase enzyme required for oestrogen synthesis was significantly associated with lower endometrial cancer risk (adjusted odd ratio [aOR] 0.87 [95% CI 0.82-0.93]; p = 6.69 × 10-5 for women across all ages and aOR 0.89 [95% CI 0.83-0.96]; p = 0.003 for postmenopausal women). None of the models that included age, body mass index (BMI), the top 10 genetic principal components, parity and diabetes mellitus explained more than 7.6% of the variation in risk. INTERPRETATION: We have shown genetic regulation of oestrone concentrations in postmenopausal women, and that SNPs associated with oestrone were also associated with endometrial cancer risk, independent of BMI, parity and diabetes mellitus. Although the apparent contribution was modest, the biological influence of oestrone concentrations may be greater through conversion to oestradiol in endometrial tissue. FUNDING: The ASPREE trial was supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (Grant U01AG029824); the National Health and Medical Research Council (NHMRC) of Australia (Grant 34047, 1127060); Monash University (Australia); and the Victorian Cancer Agency (Australia). The ASPREE Healthy Ageing Biobank was funded by the CSIRO (Flagship Grant), the National Cancer Institute (Grant U01 AG029824) and Monash University. This analysis of sex hormones was funded by an NHMRC of Australia Project Grant (No. 1105305). SRD holds an NHMRC Investigator Grant (2016627). PL is supported by a National Heart Foundation Future Leader Fellowship (102604).

Ethical applications of digital community-based research with Black immigrant and refugee youth and families.

The capacity to conduct psychology research online has expanded more quickly than have ethics guidelines for digital research. We argue that researchers must proactively plan ways to engage ethically in online psychological research with vulnerable groups, including marginalized and immigrant youth and families. To that end, this article describes the ethical use of internet and cell phone technologies in psychological research with Black immigrant and refugee youth and families, which demands efforts to both deepen and extend the Belmont principles of respect for persons, beneficence, and justice. We describe and apply four research frameworks-community-based participatory research, transdisciplinary team science, representational ethics, and cross-cultural psychology-that can be integrated to offer practical solutions to ethical challenges in digital research with Black immigrant and refugee youth and families. Then, as an illustration, we provide a case example of this approach using the Food, Culture, and Health Study conducted with Black Jamaican American and Somali American youth and families, who experience tridimensional acculturation due to their race and have been disproportionately impacted by the dual pandemics of COVID-19 and racism/Whiteness. We offer this article as a road map for other researchers seeking to conduct ethical digital community-based psychological research with Black immigrant youth and families and other marginalized communities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Associations Between Blood Concentrations of Sex Hormones and Physical Function in Community-Dwelling Older Women: A Prospective Cohort Study.

BACKGROUND: Blood concentrations of testosterone and estrone tend to increase in women aged ≥70 years, whereas concentrations of their precursor hormone dehydroepiandrosterone decline. It is unknown whether these changes influence physical function. We investigated whether concentrations of these hormones were associated with grip strength and self-reported physical function in community-dwelling older women. METHODS: A total of 9 179 Australian women, aged ≥70 years, were recruited to the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Sex hormones were measured in Sex Hormones in Older Women, an ASPREE substudy, by liquid chromatography-tandem mass spectrometry in 6 358 women. The associations between hormone concentrations and physical function (handgrip strength and self-reported physical function assessed by SF-12v2 physical component summary [PCS]) were examined using multiple linear regression. RESULTS: The median age of the 5,447 participants was 74.0 (interquartile range 71.7-77.6) years. Testosterone concentrations above the lowest quartile were associated with less decline in grip strength (mean -1.39 [95% CI -1.54 to -1.24] vs -1.75 [-2.00 to -1.50] kg, p = .02), and dehydroepiandrosterone concentrations above the lowest quartile were associated with less decline in grip strength (-1.39 [-1.54 to -1.25] vs -1.82 [-2.11 to -1.55] kg, p = .007) and PCS scores (-1.49 [-1.80 to -1.17] vs -2.33 [-2.93 to -1.72], p = .02) over 4 years, compared with those in the respective lowest quartile. CONCLUSIONS: Low endogenous concentrations of testosterone and dehydroepiandrosterone were associated the greatest likelihood of physical function decline in community-based women aged ≥70 years. Further studies are warranted to determine whether testosterone and dehydroepiandrosterone therapy prevent functional decline in this at-risk group using sensitive measures of muscle strength and performance.

Influence of genomic variations on glanders serodiagnostic antigens using integrative genomic and transcriptomic approaches.

Glanders is a highly contagious and life-threatening zoonotic disease caused by Burkholderia mallei (B. mallei). Without an effective vaccine or treatment, early diagnosis has been regarded as the most effective method to prevent glanders transmission. Currently, the diagnosis of glanders is heavily reliant on serological tests. However, given that markedly different host immune responses can be elicited by genetically different strains of the same bacterial species, infection by B. mallei, whose genome is unstable and plastic, may result in various immune responses. This variability can make the serodiagnosis of glanders challenging. Therefore, there is a need for a comprehensive understanding and assessment of how B. mallei genomic variations impact the appropriateness of specific target antigens for glanders serodiagnosis. In this study, we investigated how genomic variations in the B. mallei genome affect gene content (gene presence/absence) and expression, with a special focus on antigens used or potentially used in serodiagnosis. In all the genome sequences of B. mallei isolates available in NCBI's RefSeq database (accessed in July 2023) and in-house sequenced samples, extensive small and large variations were observed when compared to the type strain ATCC 23344. Further pan-genome analysis of those assemblies revealed variations of gene content among all available genomes of B. mallei. Specifically, differences in gene content ranging from 31 to 715 genes with an average of 334 gene presence-absence variations were found in strains with complete or chromosome-level genome assemblies, using the ATCC 23344 strain as a reference. The affected genes included some encoded proteins used as serodiagnostic antigens, which were lost due mainly to structural variations. Additionally, a transcriptomic analysis was performed using the type strain ATCC 23344 and strain Zagreb which has been widely utilized to produce glanders antigens. In total, 388 significant differentially expressed genes were identified between these two strains, including genes related to bacterial pathogenesis and virulence, some of which were associated with genomic variations, particularly structural variations. To our knowledge, this is the first comprehensive study to uncover the impacts of genetic variations of B. mallei on its gene content and expression. These differences would have significant impacts on host innate and adaptive immunity, including antibody production, during infection. This study provides novel insights into B. mallei genetic variants, knowledge which will help to improve glanders serodiagnosis.

Effect of dehydroepiandrosterone therapy on cognitive performance among postmenopausal women: a systematic review of randomized clinical trial data.

IMPORTANCE: Whether dehydroepiandrosterone (DHEA) supplementation improves cognitive performance in older women is uncertain. Nonetheless, DHEA supplements are readily available over the counter in several countries and are potentially being used to prevent cognitive decline and dementia. OBJECTIVE: This systematic review was conducted to evaluate the effect of exogenous DHEA on cognitive performance in postmenopausal women. EVIDENCE REVIEW: Ovid MEDLINE, EMBASE, PsycINFO, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials databases were searched for studies of postmenopausal women until November 30, 2022. Eligible studies were required to be randomized clinical trials, be at least single blind, have a placebo or comparator arm and published in English. Risk of bias of the included studies was assessed by the revised Cochrane risk-of-bias tool. FINDINGS: Of the 15 articles retrieved for full-text review, four met the inclusion criteria. In all studies DHEA was administered as a 50-mg oral daily dose and all were double blind with an identical placebo. Three were placebo-controlled, crossover studies and one was a parallel-group clinical trial. The only positive outcome was limited to a 4-wk cross-over study in which DHEA statistically significantly enhanced five of six tests of visual-spatial performance compared with placebo in 24 cognitively normal postmenopausal women. Improvement in cognitive performance with DHEA treatment over placebo group was not seen in any other study. Heterogeneity of design and use of multiple measures of cognitive performance was a barrier to meta-analysis and between study comparisons. The studies were limited by high risk of bias in multiple domains. CONCLUSION AND RELEVANCE: Overall, this systematic review does not support a beneficial effect of DHEA therapy on cognitive performance in postmenopausal women.

Impact of a Standardized, Pharmacist-Initiated "Test-Claim" Workflow for Anticipating Barriers to Accessing Discharge Antimicrobials.

Background: Inability to access and afford discharge oral antimicrobials may delay discharges or result in therapeutic failure. "Test-claims" have the potential to identify such barriers. Objective: This study evaluated discharge antimicrobial access and patient outcomes after implementation of a standardized, inpatient pharmacist-initiated antimicrobial discharge medication cost inquiry (aDMCI) process. Methods: This was an Institutional Review Board (IRB)-approved, pilot retrospective cohort study that included adults admitted for ≥72 hours from November 1, 2018, to February 28, 2019, and discharged on oral antimicrobials. Patients with a cost inquiry (aDMCI group) were compared with those without (standard-of-care, SOC, group). Primary endpoint was discharge delay. Secondary endpoints included percentage of patients discharged on suboptimal antimicrobials and medication errors from aDMCI. Results: 84 patients were included: 43 in SOC and 41 in aDMCI. Seventy-five antimicrobial cost inquiries were evaluated among 41 patients. There were no discharge delays or medication errors associated with the standardized "test-claim" (aDMCI) workflow. Patients in the SOC group had a greater Charlson Comorbidity Index (4 [2-6] vs 2 [1-4], P =0.004), were more likely to be immunosuppressed (24, 56% vs 12, 29%; P =0.014), and had longer hospitalization (8 [5-15] vs 6 [5-9] days, P =0.026). Primary access barriers were prior-authorization (8, 11%) and associated with linezolid and moxifloxacin cost inquiries. Most aDMCIs results were available in <24 hours (66, 88%). Conclusions: The aDMCI process is safe and offers an actionable transition of care tool that can identify barriers to accessing discharge medications while insulating patients from surprise out-of-pocket cost.

Menopause-Biology, consequences, supportive care, and therapeutic options.

Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health. The most effective treatment for bothersome menopausal symptoms is evidence-based, menopausal hormone therapy (MHT), which reduces bone loss and may have cardiometabolic benefits. Evidence-based non-hormonal interventions are also available for symptom relief. Treatment should be individualized with shared decision-making. Most MHT regimens are not regulator approved for perimenopausal women. Studies that include perimenopausal women are needed to determine the efficacy and safety of treatment options. Further research is crucial to improve menopause care, along with research to guide policy and clinical practice.

Associations between low sex hormone concentrations and depression in older women: An observational study.

OBJECTIVE: We investigated whether low sex hormone concentrations are associated with depression in older women. STUDY DESIGN: This was a cross-sectional study of Australian women, aged at least 70 years, not taking medications modulating sex hormone levels. Associations between hormones, measured by liquid chromatography-tandem mass spectrometry, and depression were examined by logistic regression adjusted for potential confounders. MAIN OUTCOME MEASURES: The primary outcome was a Center for Epidemiologic Studies Depression score >10, designated as 'depression', with an expanded definition that included anti-depressant use as a secondary outcome. RESULTS: For the 5535 participants in the analysis, median age 74.0 years (interquartile range 71.7-77.7), depression prevalence was 5.8 % (95 % CI 5.2-6.4 %). In the adjusted models, a statistically significantly greater likelihood of depression was seen for women with testosterone and oestrone blood concentrations in quartile 1 compared with quartiles 2-4 (odds ratio 1.33, 95 % CI 1.04 to 1.70, p = 0.022; and 1.37, 95 % CI 1.06 to 1.78, p = 0.017, respectively). For the expanded definition, the odds ratios for the lowest testosterone and oestrone quartile compared with other quartiles were 1.47 (95 % CI 1.24 to 1.75, p < 0.001) and 1.31 (95 % CI 1.09 to 1.58, p < 0.001), respectively. A significant association for low DHEA was seen only for the expanded definition of depression (1.36, 95 % CI 1.13 to 1.64, p = 0.001). Receiver operating characteristic curves showed that the contribution of each sex hormone to the likelihood of depression was small. CONCLUSIONS: Amongst older women not taking medications that influence sex hormone concentrations, low testosterone and oestrone levels are associated with a greater likelihood of depression, but the effects are small. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and clinicaltrials.gov (NCT01038583).

Dysmenorrhea, Workability, and Absenteeism in Australian Women.

Background: This study determined the prevalence of bothersome menstrual symptoms and their association with workability in naturally menstruating women not using hormonal contraception. Materials and Methods: A representative sample of community-dwelling Australian women aged 18-39 years selected from two large national electronic databases responded to a survey on general health. This study focuses on self-reported dysmenorrhea and menstrual bleeding and their association with workability and absenteeism in working women, assessed by the Workability Index. Results: Of 3,555 women, 1,573 (44.2% [95% CI: 42.6%-45.9%]) reported moderate to severe dysmenorrhea and 774 (21.8% [95% CI: 20.4%-23.2%]) reported heavy to very heavy bleeding. Women with dysmenorrhea were 50% more likely to report poorer work performance and twice as likely to report more days of sick leave in the past year (absenteeism) than other women. Conclusions: Despite the availability of safe and effective management options, Australian working women aged 18-39 years continue to experience bothersome dysmenorrhea and menstrual bleeding. Dysmenorrhea is associated with increased absenteeism and poorer workability. Therefore, awareness needs to be raised among women and health care providers of ways to manage dysmenorrhea and heavy bleeding and the unmet need for intervention in the community, respectively.

Special Issue "Advances in Rabies Research".

Rabies kills approximately 60,000 humans each year, with deaths mostly occurring in developing countries, where rabies lyssavirus (RABV) variants are maintained in dog populations [...].

The impact of endometriosis on work ability in young Australian women.

BACKGROUND: Whereas symptomatic endometriosis may affect work performance, the impact of endometriosis in the general community is not known. AIMS: The associations between endometriosis and each of sick leave and work ability, were investigated in a large sample of non-healthcare seeking women. MATERIALS AND METHODS: This community-based, cross-sectional study recruited 6986 women, aged 18-39 years, from three eastern states of Australia between 11 November 2016 and 21 July 2017. Women were identified as having endometriosis if they had undergone a pelvic ultrasound and reported a diagnosis of endometriosis. Working women completed the Work Ability Index. RESULTS: Participants were predominantly of European ancestry (73.1%) and 46.8% were overweight or had obesity. The prevalence of endometriosis was 5.4% (95%CI 4.9-6.0%) with the highest prevalence of 7.7% (95%CI 6.5 to 9.1%) for women aged 35-39 years. Among the 4618 working women, those with endometriosis had significantly more sick days from work (33.6% reported ≥10 days vs 13.5%, overall χ2 P < 0.001). Endometriosis was associated with a greater likelihood of poor to moderate work ability, after adjusting for age, body mass index, ethnicity, relationship status, student status, insecure housing, being a carer for another person, parity, ever use of assisted reproductive technologies, and depressed mood (odds ratio 1.90, 95%CI 1.40-2.58, P < 0.001). CONCLUSIONS: This study provides new evidence that the negative impact of endometriosis on work attendance and work ability is not limited to women with prevalent symptoms and severe disease, but appears to encompass women across a broader spectrum of this condition in the community.

Implementation of indication-based antibiotic order sentences improves antibiotic use in emergency departments.

INTRODUCTION: Prior data have suggested that suboptimal antibiotic prescribing in the emergency department (ED) is common for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). The objective of this study was to measure the effect of indication-based antibiotic order sentences (AOS) on optimal antibiotic prescribing in the ED. METHODS: This was an IRB-approved quasi-experiment of adults prescribed antibiotics in EDs for uncomplicated LRTI, UTI, or ABSSSI from January to June 2019 (pre-implementation) and September to December 2021 (post-implementation). AOS implementation occurred in July 2021. AOS are lean process, electronic discharge prescriptions retrievable by name or indication within the discharge order field. The primary outcome was optimal prescribing, defined as correct antibiotic selection, dose, and duration per local and national guidelines. Descriptive and bivariate statistics were performed; multivariable logistic regression was used to determine variables associated with optimal prescribing. RESULTS: A total of 294 patients were included: 147 pre-group and 147 post-group. Overall optimal prescribing improved from 12 (8%) to 34 (23%) (P < 0.001). Individual components of optimal prescribing were optimal selection at 90 (61%) vs 117 (80%) (P < 0.001), optimal dose at 99 (67%) vs 115 (78%) (P = 0.036), and optimal duration at 38 (26%) vs 50 (34%) (P = 0.13) for pre- and post-group, respectively. AOS was independently associated with optimal prescribing after multivariable logistic regression analysis (adjOR, 3.6; 95%CI,1.7-7.2). A post-hoc analysis showed low uptake of AOS by ED prescribers. CONCLUSIONS: AOS are an efficient and promising strategy to enhance antimicrobial stewardship in the ED.

The association between sex hormones and the change in brain-predicted age difference in older women.

OBJECTIVE: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain-predicted age difference (brain-PAD). DESIGN: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. PATIENTS: Community-dwelling older women (aged 70+ years). MEASUREMENTS: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex-hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1-weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. RESULTS: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain-PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p = .04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain-PAD cross-sectionally, nor were any of the examined sex hormones or SHBG associated with brain-PAD longitudinally. CONCLUSION: No strong evidence of an association between circulating sex hormones and brain-PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted.

Endogenous dehydroepiandrosterone and depression in postmenopausal women: a systematic review of observational studies.

IMPORTANCE: The associations between endogenous dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), and depression in older women are uncertain. However, DHEA supplements are widely available over the counter in some countries, and some people may be taking DHEA with the hope of positive mood effects. OBJECTIVE: This systematic review aimed to investigate the association between endogenous DHEA/DHEAS blood concentrations and depression/depressive symptoms in community-dwelling postmenopausal women.Evidence Review: Searches were conducted in Ovid MEDLINE, EMBASE, PsycINFO, and Web of Science databases for observational studies with at least 100 community-dwelling participants until March 9, 2022. The bibliographies of retrieved articles were manually searched. The studies published in English and meeting the inclusion criteria were included in the review. The risk of bias was assessed with the modified Hoy tool for cross-sectional designs and the Joanna Briggs Institute modified critical appraisal checklist for cohort studies. FINDINGS: Of the 30 articles retrieved for full-text review, 14 met the criteria for inclusion. Seven studies were cross-sectional, six were longitudinal, and one had both cross-sectional and longitudinal data. Five of eight cross-sectional studies found no association between DHEAS and depression, whereas three studies reported an inverse association. Similarly, most of the studies (n = 4) with longitudinal data reported no association, whereas two studies reported either an inverse association or mixed results for DHEAS and depression severity. No association between DHEA and depression was found irrespective of the study design. Heterogeneity of design was a barrier to meta-analysis and between study comparison. The majority of studies were limited by high risk of bias in at least one assessed domain. CONCLUSION AND RELEVANCE: This systematic review does not support an association between endogenous DHEA/DHEAS and depression in postmenopausal women.

Anti-Müllerian hormone for the diagnosis and prediction of menopause: a systematic review.

BACKGROUND: The early onset of menopause is associated with increased risks of cardiovascular disease and osteoporosis. As a woman's circulating anti-Müllerian hormone (AMH) concentration reflects the number of follicles remaining in the ovary and declines towards the menopause, serum AMH may be of value in the early diagnosis and prediction of age at menopause. OBJECTIVE AND RATIONALE: This systematic review was undertaken to determine whether there is evidence to support the use of AMH alone, or in conjunction with other markers, to diagnose menopause, to predict menopause, or to predict and/or diagnose premature ovarian insufficiency (POI). SEARCH METHODS: A systematic literature search for publications reporting on AMH in relation to menopause or POI was conducted in PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials up to 31 May 2022. Data were extracted and synthesized using the Synthesis Without Meta-analysis for diagnosis of menopause, prediction of menopause, prediction of menopause with a single/repeat measurement of AMH, validation of prediction models, short-term prediction in perimenopausal women, and diagnosis and prediction of POI. Risk-of-bias was evaluated using the Tool to Assess Risk of Bias in Cohort Studies protocol and studies at high risk of bias were excluded. OUTCOMES: A total of 3207 studies were identified, and 41, including 28 858 women, were deemed relevant and included. Of the three studies that assessed AMH for the diagnosis of menopause, one showed that undetectable AMH had equivalent diagnostic accuracy to elevated FSH (>22.3 mIU/ml). No study assessed whether AMH could be used to shorten the 12 months of amenorrhoea required for a formal diagnosis of menopause. Studies assessing AMH with the onset of menopause (27 publications [n = 23 835 women]) generally indicated that lower age-specific AMH concentrations are associated with an earlier age at menopause. However, AMH alone could not be used to predict age at menopause with precision (with estimates and CIs ranging from 2 to 12 years for women aged <40 years). The predictive value of AMH increased with age, as the interval of prediction (time to menopause) shortened. There was evidence that undetectable, or extremely low AMH, may aid early diagnosis of POI in young women with a family history of POI, and women presenting with primary or secondary amenorrhoea (11 studies [n = 4537]). WIDER IMPLICATIONS: The findings of this systematic review support the use of serum AMH to study the age of menopause in population studies. The increased sensitivity of current AMH assays provides improved accuracy for the prediction of imminent menopause, but diagnostic use for individual patients has not been rigorously examined. Prediction of age at menopause remains imprecise when it is not imminent, although the finding of very low AMH values in young women is both of clinical value in indicating an increased risk of developing POI and may facilitate timely diagnosis.