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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) > 3 0 and <40 kg/m2 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/m2; 95% confidence interval (Cl) 1.37 to -0.62 vs. placebo mean change 0.00; 95% Cl -0.29 to 0.28, p < 0.001). Statistically significant reductions in HbAlc (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. [ABSTRACT FROM AUTHOR]

The additive manufacturing (AM) of functional copper (Cu) parts is a major goal for many industries, from aerospace to automotive to electronics, because Cu has a high thermal and electrical conductivity as well as being ~10× cheaper than silver. Previous studies on AM of Cu have concentrated mainly on high-energy manufacturing processes such as Laser Powder Bed Fusion, Electron Beam Melting, and Binder Jetting. These processes all require high-temperature heat treatment in an oxygen-free environment. This paper shows an AM route to multi-layered microparts from novel nanoparticle (NP) Cu feedstocks, performed in an air environment, employing a low-power (<10 W) laser sintering process. Cu NP ink was deposited using two mechanisms, inkjet printing, and bar coating, followed by low-power laser exposure to induce particle consolidation. Initial parts were manufactured to a height of approximately 100 µm, which was achieved by multi-layer printing of 15 (bar-coated) to 300 (inkjetted) layers. There was no evidence of oxidised copper in the sintered material, but they were found to be low-density, porous structures. Nonetheless, electrical resistivity of ~28 × 10 -8 Ω m was achieved. Overall, the aim of this study is to offer foundational knowledge for upscaling the process to additively manufacture Cu 3D parts of significant size via sequential nanometal ink deposition and low-power laser processing., Competing Interests: The authors declare no conflicts of interest.

Domestic cats are popular companion animals, however not all live in human homes and many cats live within shelters or as free-roaming, unowned- feral or stray cats. Cats can transition between these subpopulations, but the influence of this connectivity on overall population dynamics, and the effectiveness of management interventions, remain poorly understood. We developed a UK-focused multistate Matrix Population Model (MPM), combining multiple life history parameters into an integrated model of cat demography and population dynamics. The model characterises cats according to their age, subpopulation and reproductive status, resulting in a 28-state model. We account for density-dependence, seasonality and uncertainty in our modelled projections. Through simulations, we examine the model by testing the effect of different female owned-cat neutering scenarios over a 10-year projection timespan. We also use the model to identify the vital rates to which total population growth is most sensitive. The current model framework demonstrates that increased prevalence of neutering within the owned cat subpopulation influences the population dynamics of all subpopulations. Further simulations find that neutering owned cats younger is sufficient to reduce overall population growth rate, regardless of the overall neutering prevalence. Population growth rate is most influenced by owned cat survival and fecundity. Owned cats, which made up the majority of our modelled population, have the most influence on overall population dynamics, followed by stray, feral and then shelter cats. Due to the importance of owned-cat parameters within the current model framework, we find cat population dynamics are most sensitive to shifts in owned cat husbandry. Our results provide a first evaluation of the demography of the domestic cat population in the UK and provide the first structured population model of its kind, thus contributing to a wider understanding of the importance of modelling connectivity between subpopulations. Through example scenarios we highlight the importance of studying domestic cat populations in their entirety to better understand factors influencing their dynamics and to guide management planning. The model provides a theoretical framework for further development, tailoring to specific geographies and experimental investigation of management interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 McDonald et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is limited knowledge about the effects of antipsychotic exposure on the development of gestational diabetes mellitus (GDM) in women with mental illness. Studies have demonstrated an association between antipsychotic medications and metabolic problems such as weight gain and diabetes mellitus in non-pregnant patients with psychiatric disorders. GDM increases the risk of adverse maternal outcomes, including pregnancy-induced hypertension, antepartum and postpartum haemorrhage, and caesarean delivery. The National Register of Antipsychotic Medication in Pregnancy (NRAMP) is a prospective Australian cohort study that observed women who took antipsychotics during pregnancy. Data from 205 women were extracted for the final analysis and included women who took first or second-generation antipsychotics (FGA,SGA) during the first trimester of pregnancy (at minimum) and had a diagnosis of a psychotic disorder (n = 180). The comparison (non-exposed) group (n = 25) were women with psychosis who chose not to take any antipsychotic during the first trimester (at minimum). The comparison groups were not matched, although groups were homogenous in terms of sex, age range, diagnosis and perinatal status. The results of logistic regression analysis revealed that women who were exposed to FGAs, SGAs were seven and five times, respectively, more likely to develop GDM compared to non-exposed groups. When adjusted for confounding variables such as BMI and family history of diabetes, the potential of developing GDM decreased for women taking SGAs. In conclusion, the risk of developing GDM is lower in women taking SGAs compared with women taking FDAs. In addition, family history of diabetes and BMI adds to the risk., Competing Interests: Declaration of competing interest The authors report no potential conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Humans' individual differences including their demographics, personality, attitudes and experiences are often associated with important outcomes for the animals they interact with. This is pertinent to companion animals such as cats and dogs, given their social and emotional importance to humans and degree of integration into human society. However, the mechanistic underpinnings and causal relationships that characterise links between human individual differences and companion animal behaviour and wellbeing are not well understood. In this exploratory investigation, we firstly quantified the underlying structure of, and variation in, human's styles of behaviour during typical human-cat interactions (HCI), focusing on aspects of handling and interaction known to be preferred by cats (i.e. 'best practice'), and their variation. We then explored the potential significance of various human individual differences as predictors of these HCI styles. Seven separate HCI styles were identified via Principal Component Analysis (PCA) from averaged observations for 119 participants, interacting with sociable domestic cats within a rehoming context. Using General Linear Models (GLMs) and an Information Theoretic (IT) approach, we found these HCI PC components were weakly to strongly predicted by factors including cat-ownership history, participant personality (measured via the Big Five Inventory, or BFI), age, work experience with animals and participants' subjective ratings of their cat behaviour knowledge. Paradoxically, greater cat ownership experiences and self-assessed cat knowledge were not positively associated with 'best practice' styles of HCI, but were instead generally predictive of HCI styles known to be less preferred by cats, as was greater participant age and Neuroticism. These findings have important implications regarding the quality of human-companion animal relationships and dyadic compatibility, in addition to the role of educational interventions and their targeting for optimal efficacy. In the context of animal adoption, these results strengthen the (limited) evidence base for decision making associated with cat-adopter screening and matching. In particular, our results suggest that greater cat ownership experiences and self-reports of cat knowledge might not necessarily convey advantages for cats in the context of HCI., (© 2022. The Author(s).)

Objectives: The primary objective of this review was to conduct a systematic critical appraisal of published literature, in order to assess the evidence regarding the impact of cat group size on cat wellbeing in the domestic home. The secondary objectives were to: (i) identify additional social and environmental mediators of cat wellbeing in these contexts; and (ii) identify general limitations within the current evidence and provide recommendations for future studies., Methods: A systematic search of electronic databases (Scopus, Web of Science and Google Scholar) was conducted using targeted Boolean phrasing. Papers were retained for appraisal of full text where they included a comparison of both single (n = 1) and multi-cat (n ⩾2) domestic housing conditions and/or comparison of different multi-cat group sizes, within a single study, and where they compared outcome measures that were either behavioural and/or physiological and deemed as relevant indicators of cat wellbeing., Results: A total of 1334 unique papers were returned, 15 of which were retained. Of these papers, only four stated their primary aim to be an investigation of links between cat group size and cat wellbeing. Overall, the reviewed papers did not indicate consistent directions of effects regarding cat group size and outcome measures relevant to wellbeing. This was similar for the other social and environmental mediators identified., Conclusions and Relevance: Inconsistency in results is likely due to the substantial methodological variation, limitations in measures used as indicators of wellbeing and limitations in general study designs and reporting. Results also highlight the complex, multifactorial relationships between cat wellbeing and various social and environmental factors. These may be as, if not more, important than absolute numbers of cats residing within a household. Due to the various limitations and general paucity of research, further studies are recommended to provide a suitable evidence base regarding impacts of multi-cat living on cat wellbeing in domestic environments.

The importance of animals' experiences and associated comfort during Human-Animal Interactions (HAI), and particularly Animal Assisted Interventions (AAI), are increasingly recognised. However, there remains a paucity of published research, particularly concerning less formal but frequent HAIs to which companion animals are typically exposed, such as stroking or petting. Additionally, few practical evidence-based guides to facilitate humans' optimal animal handling and interaction in these contexts exist. A simple set of Human-Cat Interaction (HCI) guidelines were therefore created, with the aim to enhance domestic cats' comfort during generic HCI contexts. Based around a "CAT" acronym, guidelines focused on providing the cat with choice and control ("C"), paying attention ("A") to the cats' behaviour and body language and limiting touch ("T"), primarily to their temporal regions. Guidelines were presented to human participants during a brief training intervention, and guideline efficacy was subsequently assessed. Domestic cats available for rehoming at Battersea Dogs and Cats Home, UK ( n = 100) were filmed during interactions with novel members of the public ( n = 120). Cats were exposed to a maximum of six, 5-min interaction sessions, balanced across "control" (interactions with humans pre-training) and "intervention" conditions (interactions with humans post-training). For each observation, cat behaviour and posture were coded and humans' cat-directed behaviour rated on the degree to which it reflected best practice principles. Data were extracted from a total of 535 observations and average human interaction ratings and cat behaviour values compared between control and intervention conditions via paired Wilcoxon tests. Compared to the control, humans' interaction styles were rated as significantly more closely aligned with best practice principles in the intervention condition. Cats also displayed significantly greater frequencies and/or durations of affiliative and positively-valenced behaviours in the intervention. In contrast, cats in the control displayed significantly greater frequencies of human-directed aggression, in addition to greater frequencies and/or durations of behaviours associated with conflict and negative valence. Results demonstrate the positive impact of practical interaction guidelines on cats' social behaviour and comfort during HCI, with the potential to improve cats' general experiences during interactions, reduce human-directed aggression and ultimately improve cat-human relationships., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Haywood, Ripari, Puzzo, Foreman-Worsley and Finka.)

Outdoor access for owned domestic cats ( Felis catus ) is a divisive issue. Cat safety, mental and physical wellbeing, infectious diseases, and wildlife depredation are cited as factors influencing owners; however, the degree of consideration each factor receives has not been quantified. This study (i) analysed which demographic variables are associated with greater odds of cats having indoor or outdoor lifestyles, (ii) identified which factors owners consider when making a choice on lifestyle and any regional variations, and (iii) identified if owners consider the different lifestyle options available and recognise their associated benefits. A series of online surveys were used for data collection. Binary logistic regression models were used to generate odds ratios assessing if demographic variables were significantly associated with cat lifestyle. Quantitative analysis of factors considered when deciding on cat lifestyle was accompanied by a thematic analysis of rich-text open-ended responses, providing nuanced insight into the rationale and elucidating additional factors considered. Of the demographic variables tested, 10/12 were significantly associated with lifestyle. Variables with higher odds of indoor-only lifestyles were owners being 26-35 years old, multi-cat households, junior cats, pedigree cats or unknown pedigree status, cats with health issues, living in city centres or urban areas, or living in the United States, Canada, Australia, or New Zealand. Variables with higher odds of indoor-outdoor lifestyles were owners being 46-55 years old or 56+ years old, households with residents 17 years old or under, male cats, and cats being mature or senior. Road traffic concerns were the most cited reason for keeping indoor-only cats across all global regions. The second-most cited reason varied regionally. For Europe, it was protection from people. For the USA and Canada, the reason was protection from wildlife, and for Australia and New Zealand, to prevent hunting. Indoor-outdoor cat owners cited most frequently the benefits to their cat's mental health. Over two-thirds of owners did not consider the alternative lifestyle for their cat. These data give insight into the priorities of cat owners with regards to feline wellbeing, feline safety, and wildlife depredation, helpful for individuals or organisations working with human behaviour change. They provide evidence that the numbers of indoor-only cats are likely to rise with increasing urbanisation. Finally, the data identify cat populations who may be at risk of compromised welfare due to unsuitable, or under-researched, lifestyles.

Graphene oxide (GO), an oxidised form of graphene, is widely used for biomedical applications, due to its dispersibility in water and simple surface chemistry tunability. In particular, small (less than 500 nm in lateral dimension) and thin (1-3 carbon monolayers) graphene oxide nanosheets (s-GO) have been shown to selectively inhibit glutamatergic transmission in neuronal cultures in vitro and in brain explants obtained from animals injected with the nanomaterial. This raises the exciting prospect that s-GO can be developed as a platform for novel nervous system therapeutics. It has not yet been investigated whether the interference of the nanomaterial with neurotransmission may have a downstream outcome in modulation of behaviour depending specifically on the activation of those synapses. To address this problem we use early stage zebrafish as an in vivo model to study the impact of s-GO on nervous system function. Microinjection of s-GO into the embryonic zebrafish spinal cord selectively reduces the excitatory synaptic transmission of the spinal network, monitored in vivo through patch clamp recordings, without affecting spinal cell survival. This effect is accompanied by a perturbation in the swimming activity of larvae, which is the locomotor behaviour generated by the neuronal network of the spinal cord. Such results indicate that the impact of s-GO on glutamate based neuronal transmission is preserved in vivo and can induce changes in animal behaviour. These findings pave the way for use of s-GO as a modulator of nervous system function.

Paper is the ideal substrate for the development of flexible and environmentally sustainable ubiquitous electronic systems, which, combined with two-dimensional materials, could be exploited in many Internet-of-Things applications, ranging from wearable electronics to smart packaging. Here we report high-performance MoS 2 field-effect transistors on paper fabricated with a "channel array" approach, combining the advantages of two large-area techniques: chemical vapor deposition and inkjet-printing. The first allows the pre-deposition of a pattern of MoS 2 ; the second, the printing of dielectric layers, contacts, and connections to complete transistors and circuits fabrication. Average I ON /I OFF of 8 × 10 3 (up to 5 × 10 4 ) and mobility of 5.5 cm 2 V -1 s -1 (up to 26 cm 2 V -1 s -1 ) are obtained. Fully functional integrated circuits of digital and analog building blocks, such as logic gates and current mirrors, are demonstrated, highlighting the potential of this approach for ubiquitous electronics on paper.

We report room temperature Hall mobility measurements, low temperature magnetoresistance analysis and low-frequency noise characterization of inkjet-printed graphene films on fused quartz and SiO 2 /Si substrates. We found that thermal annealing in vacuum at 450 °C is a necessary step in order to stabilize the Hall voltage across the devices, allowing their electrical characterization. The printed films present a minimum sheet resistance of 23.3 Ω sq -1 after annealing, and are n-type doped, with carrier concentrations in the low 10 20 cm -3 range. The charge carrier mobility is found to increase with increasing film thickness, reaching a maximum value of 33 cm 2 V -1 s -1 for a 480 nm-thick film printed on SiO 2 /Si. Low-frequency noise characterization shows a 1/f noise behavior and a Hooge parameter in the range of 0.1-1. These results represent the first in-depth electrical and noise characterization of transport in inkjet-printed graphene films, able to provide physical insights on the mechanisms at play.

Oral contraceptives (OCs) containing estrogen and progesterone analogues are widely used amongst reproductive-aged women, but their neurocognitive impact is poorly understood. Preliminary studies suggest that OCs improve verbal memory and that OCs with greater androgenic activity may improve visuospatial ability. We sought to explore the cognitive impact of OCs by assessing performance of OC users at different stages of the OC cycle, and comparing this performance between users of different OC formulations according to known androgenic activity. We conducted a prospective, observational trial of OC users, evaluating cognitive performance with CogState software on two occasions: days 7-10 of active hormonal pill phase, and days 3-5 of the inactive pill phase (coinciding with the withdrawal bleed resembling menstruation). Thirty-five OC users (18 taking androgenic formulations, 17 taking anti-androgenic) were assessed. Analysis by androgenic activity showed superior performance by users of androgenic OCs, as compared to anti-androgenic OCs, in visuospatial ability and facial affect discrimination tasks. A growing understanding of cognitive effects of OC progestin androgenicity may have implications in choice of OC formulation for individuals and in future OC development., Competing Interests: The authors declare no conflict of interest.

Semiconducting carbon nanotubes (CNTs) printed into thin films offer high electrical performance, significant mechanical stability, and compatibility with low-temperature processing. Yet, the implementation of low-temperature printed devices, such as CNT thin-film transistors (CNT-TFTs), has been hindered by relatively high process temperature requirements imposed by other device layers-dielectrics and contacts. In this work, we overcome temperature constraints and demonstrate 1D-2D thin-film transistors (1D-2D TFTs) in a low-temperature (maximum exposure ≤80 °C) full print-in-place process ( i.e. , no substrate removal from printer throughout the entire process) using an aerosol jet printer. Semiconducting 1D CNT channels are used with a 2D hexagonal boron nitride (h-BN) gate dielectric and traces of silver nanowires as the conductive electrodes, all deposited using the same printer. The aerosol jet-printed 2D h-BN films were realized via proper ink formulation, such as utilizing the binder hydroxypropyl methylcellulose, which suppresses redispersion between adjacent printed layers. In addition to an ON/OFF current ratio up to 3.5 × 10 5 , channel mobility up to 10.7 cm 2 ·V -1 ·s -1 , and low gate hysteresis, 1D-2D TFTs exhibit extraordinary mechanical stability under bending due to the nanoscale network structure of each layer, with minimal changes in performance after 1000 bending test cycles at 2.1% strain. It is also confirmed that none of the device layers require high-temperature treatment to realize optimal performance. These findings provide an attractive approach toward a cost-effective, direct-write realization of electronics.

A well-defined insulating layer is of primary importance in the fabrication of passive ( e.g., capacitors) and active ( e.g., transistors) components in integrated circuits. One of the most widely known two-dimensional (2D) dielectric materials is hexagonal boron nitride (hBN). Solution-based techniques are cost-effective and allow simple methods to be used for device fabrication. In particular, inkjet printing is a low-cost, noncontact approach, which also allows for device design flexibility, produces no material wastage, and offers compatibility with almost any surface of interest, including flexible substrates. In this work, we use water-based and biocompatible graphene and hBN inks to fabricate all-2D material and inkjet-printed capacitors. We demonstrate an areal capacitance of 2.0 ± 0.3 nF cm -2 for a dielectric thickness of ∼3 μm and negligible leakage currents, averaged across more than 100 devices. This gives rise to a derived dielectric constant of 6.1 ± 1.7. The inkjet printed hBN dielectric has a breakdown field of 1.9 ± 0.3 MV cm -1 . Fully printed capacitors with sub-micrometer hBN layer thicknesses have also been demonstrated. The capacitors are then exploited in two fully printed demonstrators: a resistor-capacitor (RC) low-pass filter and a graphene-based field effect transistor.

Objective: This study aims to determine the prevalence and severity of menopausal symptoms in older postmenopausal women and, hence, the need for treatment options for women of this age., Methods: This is a cross-sectional questionnaire-based study conducted between October 2013 and March 2014 among 2,020 women aged 40 to 65 years and living independently across Australia. The main outcome measures were the prevalence of moderate to severe vasomotor symptoms (VMS), as measured by the Menopause-Specific Quality of Life Questionnaire, and the current use of prescription therapy for menopausal symptoms., Results: The prevalence of moderate to severe VMS was as follows: 2.8% in premenopausal women, 17.1% in perimenopausal women, 28.5% in postmenopausal women younger than 55 years, 15.1% in postmenopausal women aged 55 to 59 years, and 6.5% in postmenopausal women aged 60 to 65 years. Prescription therapy for menopausal symptoms was used by 135 women: 120 (5.9%) women using hormone therapy and 15 (0.7%) women using nonhormonal medication. The factors positively associated with moderate to severe VMS were smoking (odds ratio, 1.6; 95% CI, 1.1-2.3; P < 0.05) and a body mass index of 25 to 29.9 kg/m (odds ratio, 1.7; 95% CI, 1.1-2.5; P < 0.05); education beyond high school was inversely associated (odds ratio, 0.7; 95% CI, 0.5-0.9; P < 0.05)., Conclusions: In this large, representative, community-based sample of women, there is a high prevalence of untreated moderate to severe VMS even in women aged 60 to 65 years. The use of vaginal estrogen and nonhormonal prescription therapy with proven efficacy for treatment of menopausal symptoms is strikingly low, suggesting that menopause remains an undertreated condition.

Background: Many women with no past psychiatric history experience severe mood symptoms for the first time in their life during the menopausal transition, with debilitating long-term consequences. Women with a history of depression can experience a relapse or worsening of symptoms during the menopause transition. Traditional antidepressants, SSRIs or SNRIs, are commonly prescribed as the first line response. However, such treatment has shown only small improvements with side effects. Hormone therapies directly targeting the perimenopausal fluctuations in reproductive hormonal systems such as tibolone, have significant potential to treat perimenopausal depression. Our study investigated the use of adjunctive tibolone, selective tissue estrogenic activity regulator, to treat de-novo or relapsing depression occurring during the menopause transition period., Methods: Women who were going through the menopause transition with depressive symptoms were invited to participate in a double-blind, 12 week randomized control trial with two arms: tibolone (2.5 mg oral/day) or oral placebo (NCT01470092). Forty-four women met inclusion/exclusion criteria; 22 were randomized to tibolone and 22 were randomized to oral placebo. Symptoms were measured with the 'Montgomery- Asberg depression rating scale' (MADRS) as the primary outcome measure. Latent growth curve analysis was used to assess the MADRS scores change over time., Results: Participants in the tibolone group demonstrated a significant improvement in depression scores, as compared to the placebo group, without any significant side effects., Limitations: This trial only monitored tibolone's effects over 12 weeks. Future research should be conducted over an extended timeframe and explore whether the benefits of tibolone extend to other symptoms of perimenopausal depression., Conclusions: The use of hormone therapies such as tibolone provide exciting innovations for the treatment of depression during the menopause transition., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The menopause transition is a time when women experience an increased risk for new onset depression, as well as relapse of depression. While there are overlapping symptoms between major depression and depression during menopause, differences suggest 'perimenopausal depression' may be a unique subtype of depression associated with characteristic symptoms. There is currently no validated scale designed to measure perimenopausal depression. The aim of the current study was to develop and validate the 'Meno-D', a self-reporting or clinician rated questionnaire, designed to rate the severity of symptoms of perimenopausal depression. The development phase of the Meno-D involved literature review, clinical observation, and focus groups. A 12-item questionnaire was developed and clinically reviewed for face validity for content. The Meno-D was administered to women experiencing symptoms of perimenopausal depression as part of a larger baseline assessment battery. Validation involved confirmatory factor analysis (CFA). The development of the Meno-D resulted in 12 items. A total of 93 participants with perimenopausal depression were involved in the baseline assessments, 82 completed the Meno-D. Factor analysis identified five sub-scales of the Meno-D "somatic; cognitive; self; sleep; sexual" with high-internal consistency; discriminant validity and a good construct and convergent validity. The Meno-D provides a unique tool for clinicians and researchers to measure the presence of perimenopausal depression.

Rationale: Hyperprolactinemia is a highly prevalent adverse effect of many antipsychotic agents, with potentially serious health consequences. Several guidelines have been developed for the management of this condition; yet, their concordance has not been evaluated., Objectives: The objectives of this paper were (1) to review current clinical guidelines; (2) to review key systematic evidence for management; and (3) based on our findings, to develop an integrated management recommendation specific to male and female patients who are otherwise clinically stabilised on antipsychotics., Methods: We performed searches of Medline and EMBASE, supplemented with guideline-specific database and general web searches, to identify clinical guidelines containing specific recommendations for antipsychotic-induced hyperprolactinemia, produced/updated 01/01/2010-15/09/2016. A separate systematic search was performed to identify emerging management approaches described in reviews and meta-analyses published ≥ 2010., Results: There is some consensus among guidelines relating to baseline PRL screening (8/12 guidelines), screening for differential diagnosis (7/12) and discontinuing/switching PRL-raising agent (7/12). Guidelines otherwise diverge substantially regarding most aspects of screening, monitoring and management (e.g. treatment with dopamine agonists). There is an omission of clear sex-specific recommendations. Systematic literature on management approaches is promising; more research is needed. An integrated management recommendation is presented to guide sex-specific clinical response to antipsychotic-induced hyperprolactinemia. Key aspects include asymptomatic hyperprolactinemia monitoring and fertility considerations with PRL normalisation., Conclusion: Further empirical work is key to shaping robust guidelines for antipsychotic-induced hyperprolactinemia. The integrated management recommendation can assist clinician and patient decision-making, with the goal of balancing effective psychiatric treatment while minimising PRL-related adverse health effects in male and female patients.

Background: The association between menopausal vasomotor symptoms (VMS) and depressive symptoms remains controversial. We aimed to examine the associations between moderate-severe VMS and moderate-severe depressive symptoms., Methods: Nationally representative cross-sectional survey of 2,020 noninstitutionalized Australian women aged 40-65 randomly recruited between October 2013 and March 2014. Symptoms were assessed by the Menopause-Specific Quality of Life Questionnaire, the Beck Depression Inventory-II, with score ≥20 defined as moderate-severe depressive symptoms. Cigarette, alcohol, and psychotropic medication use was also assessed. Binge drinking was defined as four standard drinks on one occasion., Results: VMS were classified as moderate-severe for 267 of the 2,020 women (13.3%). After adjusting for multiple factors, including age, partnership status, paid employment, housing insecurity, and body mass index, when compared to women with no or mild VMS, women with moderate-severe VMS were more likely to have moderate-severe depressive symptoms (odds ratio [OR] 2.80, confidence interval [95% CI], 2.01-3.88, p < 0.001). Having moderate-severe depressive symptoms was associated with a greater likelihood of use of psychotropic medications (48.9%, 95% CI, 43.1-54.8 vs. 20.1%, 95% CI, 18.2-22.1, p < 0.001), smoking (25.9%, 95% CI, 20.8-30.9 vs. 12.2%, 95% CI, 10.6-13.7, p < 0.001), and binge drinking at least weekly (15.1%, 95% CI, 11.0-19.2 vs. 10.3% 95% CI, 8.8-11.7, p = 0.015)., Conclusion: Moderate-severe VMS are independently and significantly associated with moderate-severe depressive symptoms.

Background: Low desire is the most common sexual problem in women at midlife. Prevalence data are limited by lack of validated instruments or exclusion of un-partnered or sexually inactive women., Aim: To document the prevalence of and factors associated with low desire, sexually related personal distress, and hypoactive sexual desire dysfunction (HSDD) using validated instruments., Methods: Cross-sectional, nationally representative, community-based sample of 2,020 Australian women 40 to 65 years old., Outcomes: Low desire was defined as a score no higher than 5.0 on the desire domain of the Female Sexual Function Index (FSFI); sexually related personal distress was defined as a score of at least 11.0 on the Female Sexual Distress Scale-Revised; and HSDD was defined as a combination of these scores. The Menopause Specific Quality of Life Questionnaire was used to document menopausal vasomotor symptoms. The Beck Depression Inventory-II was used to identify moderate to severe depressive symptoms (score ≥ 20)., Results: The prevalence of low desire was 69.3% (95% CI = 67.3-71.3), that of sexually related personal distress was 40.5% (95% CI = 38.4-42.6), and that of HSDD was 32.2% (95% CI = 30.1-34.2). Of women who were not partnered or sexually active, 32.4% (95% CI = 24.4-40.2) reported sexually related personal distress. Factors associated with HSDD in an adjusted logistic regression model included being partnered (odds ratio [OR] = 3.30, 95% CI = 2.46-4.41), consuming alcohol (OR = 1.48, 95% CI = 1.16-1.89), vaginal dryness (OR = 2.08, 95% CI = 1.66-2.61), pain during or after intercourse (OR = 1.63, 95% CI = 1.27-2.09), moderate to severe depressive symptoms (OR = 2.69, 95% CI 1.99-3.64), and use of psychotropic medication (OR = 1.42, 95% CI = 1.10-1.83). Vasomotor symptoms were not associated with low desire, sexually related personal distress, or HSDD., Clinical Implications: Given the high prevalence, clinicians should screen midlife women for HSDD., Strengths and Limitations: Strengths include the large size and representative nature of the sample and the use of validated tools. Limitations include the requirement to complete a written questionnaire in English. Questions within the FSFI limit the applicability of FSFI total scores, but not desire domain scores, in recently sexually inactive women, women without a partner, and women who do not engage in penetrative intercourse., Conclusions: Low desire, sexually related personal distress, and HSDD are common in women at midlife, including women who are un-partnered or sexually inactive. Some factors associated with HSDD, such as psychotropic medication use and vaginal dryness, are modifiable or can be treated with safe and effective therapies. Worsley R, Bell RJ, Gartoulla P, Davis SR. Prevalence and Predictors of Low Sexual Desire, Sexually Related Personal Distress, and Hypoactive Sexual Desire Dysfunction in a Community-Based Sample of Midlife Women. J Sex Med 2017;14:675-686., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The objective of the International Society for the Study of Women's Sexual Health expert consensus panel was to develop a concise, clinically relevant, evidence-based review of the epidemiology, physiology, pathogenesis, diagnosis, and treatment of hypoactive sexual desire disorder (HSDD), a sexual dysfunction affecting approximately 10% of adult women. Etiologic factors include conditions or drugs that decrease brain dopamine, melanocortin, oxytocin, and norepinephrine levels and augment brain serotonin, endocannabinoid, prolactin, and opioid levels. Symptoms include lack or loss of motivation to participate in sexual activity due to absent or decreased spontaneous desire, sexual desire in response to erotic cues or stimulation, or ability to maintain desire or interest through sexual activity for at least 6 months, with accompanying distress. Treatment follows a biopsychosocial model and is guided by history and assessment of symptoms. Sex therapy has been the standard treatment, although there is a paucity of studies assessing efficacy, except for mindfulness-based cognitive behavior therapy. Bupropion and buspirone may be considered off-label treatments for HSDD, despite limited safety and efficacy data. Menopausal women with HSDD may benefit from off-label testosterone treatment, as evidenced by multiple clinical trials reporting some efficacy and short-term safety. Currently, flibanserin is the only Food and Drug Administration-approved medication to treat premenopausal women with generalized acquired HSDD. Based on existing data, we hypothesize that all these therapies alter central inhibitory and excitatory pathways. In conclusion, HSDD significantly affects quality of life in women and can effectively be managed by health care providers with appropriate assessments and individualized treatments., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Importance: A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects., Objective: To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia., Design, Setting, and Participants: This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis., Interventions: Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks., Main Outcomes and Measures: The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed., Results: Of the 56 participants (mean [SD] age, 53 [7.7] years; age range, 40-70 years; mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37; 95% CI, -11.64 to -1.10; P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79; 95% CI, 1.46 to 22.97; P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72; 95% CI, -6.83 to -0.61; P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92; 95% CI, -3.83 to 0.00; P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups., Conclusions and Relevance: Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice., Trial Registration: clinicaltrials.gov Identifier: NCT00361543.