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Context The time course of male reproductive hormone recovery after stopping injectable testosterone undecanoate (TU) treatment is not known. Objective The aim of this study was to investigate the rate, extent, and determinants of reproductive hormone recovery over 12 months after stopping TU injections. Materials and Methods Men (n = 303) with glucose intolerance but without pathologic hypogonadism who completed a 2-year placebo (P)-controlled randomized clinical trial of TU treatment were recruited for further 12 months while remaining blinded to treatment. Sex steroids (testosterone (T), dihydrotestosterone, oestradiol, oestrone) by liquid chromatography-mass sprectometry, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) by immunoassays and sexual function questionnaires (Psychosexual Diary Questionnaire, International Index of Erectile Function, and short form survey (SF-12)) were measured at entry (3 months after the last injection) and 6, 12, 18, 24, 40, and 52 weeks later. Results In the nested cohort of TU-treated men, serum T was initially higher but declined at 12 weeks remaining stable thereafter with serum T and SHBG at 11 and 13%, respectively, lower than P-treated men. Similarly, both questionnaires showed initial carry-over higher scores in T-treated men but after 18 weeks showed no difference between T- and P-treated men. Initially, fully suppressed serum LH and FSH recovered slowly towards the participant’s own pre-treatment baseline over 12 months since the last injection. Conclusions After stopping 2 years of 1000 mg injectable TU treatment, full reproductive hormone recovery is slow and progressive over 15 months since the last testosterone injection but may take longer than 12 months to be complete. Persistent proportionate reduction in serum SHBG and T reflects lasting exogenous T effects on hepatic SHBG secretion rather than androgen deficiency.

BACKGROUND Breast arterial calcification (BAC) is a common incidental finding on screening mammography. Recent evidence suggests that BAC is associated with cardiovascular disease (CVD). We systematically reviewed the associations between BAC and reproductive factors (menopausal status, hormone replacement therapy [HRT] use, oral contraceptive [OC] use and parity). METHODS MEDLINE and EMBASE databases, references of relevant papers and Web of Science were searched up to February 2020 for English-language studies that evaluated these associations. Study quality were determined and a random effects model was used to assess these associations. RESULTS Nineteen observational studies (n = 47,249; three cohort studies, seven case-control studies, nine cross-sectional studies) were included. BAC was associated with menopause (nine studies; n = 15,870; odds ratio [OR] 2.67; 95% confidence interval [CI] 1.50-4.77) and parity (seven studies; n = 27,728; OR 2.50; 95% CI 1.68-3.71) and inversely with HRT use (10 studies; n = 33,156; OR 0.57; 95% CI 0.40-0.80). No association was found with OC use. Eleven studies were considered good in quality. Marked heterogeneity existed across all analyses. CONCLUSIONS BAC is associated with HRT use, menopause and parity. However, careful interpretation is required as marked heterogeneity existed across all analyses. Traditional cardiovascular risk factors may need to be taken into account in future investigations of associations between BAC and reproductive factors. PROSPERO CRD42020141644.

Vasomotor symptoms (hot flushes and night sweats) are experienced by more than two-thirds of women with breast cancer taking oral adjuvant endocrine therapy. Safe and effective treatments are lacking. Q-122 is a novel, non-hormonal compound that has shown promise for reducing vasomotor symptoms by modulation of oestrogen-responsive neurons in the hypothalamus. We aimed to assess the efficacy and safety of Q-122 in women with breast cancer taking oral adjuvant endocrine therapy and experiencing vasomotor symptoms.We conducted a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial at 18 sites in Australia, New Zealand, and the USA. Eligible participants were women, aged 18-70 years, taking a stable dose of tamoxifen or an aromatase inhibitor following breast cancer and experiencing at least 50 self-reported moderate to severe vasomotor symptoms per week. Participants were randomly assigned (1:1) using an interactive web response system to oral Q-122 100 mg or identical placebo, twice daily for 28 days. Randomisation was stratified by BMI (≤30 kg/msup2/suporgt;30 kg/msup2/sup) and use of any of a selective serotonin reuptake inhibitor, selective norepinephrine reuptake inhibitor, gabapentin, or pregabalin. Q-122 and placebo capsules were identical in appearance and containers identically labelled. During the double-blind treatment and analysis phases, the participants, investigators, clinical research organisation staff, and sponsor were masked to treatment allocation. The primary outcome was the difference in the mean percentage change from baseline in the Vasomotor Symptom Severity Score of moderate and severe hot flushes and night sweats (msVMS-SS) between Q-122 and placebo after 28 days of treatment. Primary analysis was by modified intention-to-treat and safety was assessed in all participants receiving at least one dose of study drug. This study is registered at ClinicalTrials.gov, NCT03518138.Between Oct 24, 2018, and Sept 9, 2020, 243 patients were screened, 131 of whom were randomly assigned and received treatment (Q-122 n=65 and placebo n=66). Q-122 resulted in a significantly greater mean percentage change in msVMS-SS from baseline over 28 days of treatment compared with placebo (least squares mean: Q-122 -39% [95% CI -46 to -31] vs placebo -26% [-33 to -18]; p=0·018). Treatment-emergent adverse events were generally mild to moderate and similar between the two groups (treatment-related treatment-emergent adverse events in 11 [17%] of 65 patients in the Q-122 group vs nine [14%] of 66 in the placebo group); zero patients in the Q-122 group and two (3%) patients in the placebo group had serious adverse events.Q-122 is an effective and well tolerated non-hormonal oral treatment for vasomotor symptoms in women taking oral adjuvant endocrine therapy after breast cancer. Our results support the conduct of larger and longer studies of Q-122, with potential use extending to postmenopausal women who require an alternative to menopausal hormone therapy.QUE Oncology.

Context Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. Objective We aimed to determine the effect of testosterone treatment on bone microarchitecture using high resolution–peripheral quantitative computed tomography (HR-pQCT). Methods Men ≥ 50 years of age were recruited from 6 Australian centers and were randomized to receive injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. The primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (1 center). Secondary endpoints included other HR-pQCT parameters and bone remodeling markers. Areal BMD (aBMD) was measured by dual-energy x-ray absorptiometry (DXA) in 601 men (5 centers). Using a linear mixed model for repeated measures, the mean adjusted differences (95% CI) at 12 and 24 months between groups are reported as treatment effect. Results Over 24 months, testosterone treatment, versus placebo, increased tibial cortical vBMD, 9.33 mg hydroxyapatite (HA)/cm3) (3.96, 14.71), P Conclusion In men ≥ 50 years of age, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.

A 28-year-old man with congenital hypogonadotropic hypogonadism (CHH) was found to be heterozygous for the GNRH1 p.R31C mutation, reported in the literature as pathogenic and dominant. The same mutation was found in his son at birth, but the testing of the infant at 64 days confirmed the hormonal changes associated with minipuberty. This led to further genetic sequencing of the patient and his son, which found a second variant, AMHR2 p.G445_L453del, in the heterozygous form, reported as pathogenic in the patient but not in his son. This suggests a digenic cause of the patient’s CHH. Together, these mutations are postulated to contribute to CHH by the lack of anti-Müllerian hormone (AMH) signalling, leading to the impaired migration of gonadotrophin releasing hormone (GnRH) neurons, the lack of the AMH effect on GnRH secretion, and altered GnRH decapeptide with reduced binding to GnRH receptors. This led us to the conclusion that the observed GNRH1 mutation in the heterozygous state is not certain to be dominant or, at least, exhibits incomplete penetrance and variable expressivity. This report also emphasises the opportunity afforded by the time window of minipuberty in assessing the inherited genetic disorders of hypothalamic function.

Summary Background Men who are overweight or obese frequently have low serum testosterone concentrations, which are associated with increased risk of type 2 diabetes. We aimed to determine whether testosterone treatment prevents progression to or reverses early type 2 diabetes, beyond the effects of a community-based lifestyle programme. Methods T4DM was a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial done at six Australian tertiary care centres. Men aged 50–74 years, with a waist circumference of 95 cm or higher, a serum testosterone concentration of 14·0 nmol/L or lower but without pathological hypogonadism, and impaired glucose tolerance (oral glucose tolerance test [OGTT] 2-h glucose 7·8–11·0 mmol/L) or newly diagnosed type 2 diabetes (provided OGTT 2-h glucose ≤15·0 mmol/L) were enrolled in a lifestyle programme and randomly assigned (1:1) to receive an intramuscular injection of testosterone undecanoate (1000 mg) or placebo at baseline, 6 weeks, and then every 3 months for 2 years. Randomisation was done centrally, including stratification by centre, age group, waist circumference, 2-h OGTT glucose, smoking, and first-degree family history of type 2 diabetes. The primary outcomes at 2 years were type 2 diabetes (2-h OGTT glucose ≥11·1 mmol/L) and mean change from baseline in 2-h OGTT glucose, assessed by intention to treat. For safety assessment, we did a masked monitoring of haematocrit and prostate-specific antigen, and analysed prespecified serious adverse events. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000287831. Findings Between Feb 5, 2013, and Feb 27, 2017, of 19 022 men who were pre-screened, 1007 (5%) were randomly assigned to the placebo (n=503) and testosterone (n=504) groups. At 2 years, 2-h glucose of 11·1 mmol/L or higher on OGTT was reported in 87 (21%) of 413 participants with available data in the placebo group and 55 (12%) of 443 participants in the testosterone group (relative risk 0·59, 95% CI 0·43 to 0·80; p=0·0007). The mean change from baseline 2-h glucose was −0·95 mmol/L (SD 2·78) in the placebo group and −1·70 mmol/L (SD 2·47) in the testosterone group (mean difference −0·75 mmol/L, −1·10 to −0·40; p Interpretation Testosterone treatment for 2 years reduced the proportion of participants with type 2 diabetes beyond the effects of a lifestyle programme. Increases in haematocrit might be treatment limiting. Longer-term durability, safety, and cardiovascular effects of the intervention remain to be further investigated. Funding Australian National Health and Medical Research Council, Bayer, Eli Lilly, University of Adelaide, and WW (formerly Weight Watchers).

Malabsorption due to celiac disease (CD) may contribute to postmenopausal osteoporosis. This study aimed to survey participants with CD regarding their bone density, fractures, and bone-preserving medications; to compare tolerance of bone-preserving medications in participants with and without CD; and to review the evidence for CD screening and osteoporosis therapies in the setting of CD. We recruited 131 participants with CD and 102 participants without CD. Of those with CD, 87% were diagnosed in adulthood and 40% had no recognized gastrointestinal symptoms. In 21% CD was diagnosed after the diagnosis of osteoporosis and in 9% after a fracture. No difference was found in the tolerability of bone medications between participants with CD and those without. Review of the literature found that, although monitoring of bone health is recommended for patients with CD, screening for CD is not generally accepted for patients with osteoporosis, although studies of the prevalence of CD in osteoporosis had incomplete ascertainment methods. There is a lack of well-conducted studies and therefore insufficient data for the efficacy and tolerability of bone medication in CD. In conclusion, both CD and menopause lead to bone loss. Identifying CD in postmenopausal women should lead to modification of osteoporosis management.

Aim: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D). Materials and Methods: This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks, followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies. Results: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups. Conclusions: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of β-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.

Objectives The aim of the study was to compare the response rates and costs of phone call vs. short message service (SMS) screening reminders to prospective randomized controlled trial (RCT) participants. Study Design and Setting This study was a randomized evaluation within a large Australian diabetes prevention RCT. Participants were men aged 50–74 years, overweight or obese, without a previous type 2 diabetes diagnosis. Those eligible on a prescreening questionnaire who did not attend a further screening assessment within 4 weeks were randomized to receive an SMS or phone call reminder (N = 709). The primary outcome was attendance for further screening assessment within 8 weeks of prescreening. Results Attendance was 18% (62/354) in the SMS reminder group, and 23% (80/355) in the phone reminder group, with no statistically significant difference in response according to reminder type (relative risk = 1.29, 95% confidence interval [CI]: 0.96–1.73, P = 0.09). The lower confidence limits for response to SMS (95% CI: 14–22%) and phone reminders (95% CI: 18–27%) did not include the 8-week attendance rate before this evaluation, 12%. Phone reminders cost substantially more than SMS reminders (AU$6.21 vs. AU$0.53 per reminder). Conclusion SMS reminders were as adequate a method as phone reminders to boost RCT screening uptake and were considerably more affordable.

Background Menopause is a time of change in women's lives and an opportunity for health promotion. Women can present with a range of symptoms and concerns. Objective The aim of this article is to review the key components of the assessment of women who are perimenopausal or menopausal, and to discuss the benefits and risks of hormonal and non-hormonal treatments, thereby assisting clinicians to appropriately manage these women. Discussion The majority of women who are symptomatic can be offered menopausal hormone therapy (MHT). To ensure women can make an informed choice about whether to use MHT, it is important for them to receive balanced and accurate information about the benefits and risks. For women with contraindications to MHT, or women who prefer not to use hormones, non-hormonal and complementary options may be considered. New non-hormonal options are likely to be available in the future.

Background Effective interventions are required to prevent the current rapid increase in the prevalence of Type 2 diabetes. Clinical trials of large-scale interventions to prevent Type 2 diabetes are essential but recruitment is challenging and expensive, and there are limited data regarding the most cost-effective and efficient approaches to recruitment. This paper aims to evaluate the cost and effectiveness of a range of promotional strategies used to recruit men to a large Type 2 diabetes prevention trial. Methods An observational study was conducted nested within the Testosterone for the Prevention of Type 2 Diabetes (T4DM) study, a large, multi-centre randomised controlled trial (RCT) of testosterone treatment for the prevention of Type 2 diabetes in men aged 50–74 years at high risk of developing diabetes. Study participation was promoted via mainstream media—television, newspaper and radio; direct marketing using mass mail-outs, publicly displayed posters and attendance at local events; digital platforms, including Facebook and Google; and online promotions by community organisations and businesses. For each strategy, the resulting number of participants and the direct cost involved were recorded. The staff effort required for each strategy was estimated based on feedback from staff. Results Of 19,022 men screened for the study, 1007 (5%) were enrolled. The most effective recruitment strategies were targeted radio advertising (accounting for 42% of participants), television news coverage (20%) and mass mail-outs (17%). Other strategies, including radio news, publicly displayed posters, attendance at local events, newspaper advertising, online promotions and Google and Facebook advertising, each accounted for no more than 4% of enrolled participants. Recruitment promotions cost an average of AU$594 per randomised participant. The most cost-effective paid strategy was mass mail-outs by a government health agency (AU$745 per participant). Other paid strategies were more expensive: mail-out by general practitioners (GPs) (AU$1104 per participant), radio advertising (AU$1081) and newspaper advertising (AU$1941). Conclusion Radio advertising, television news coverage and mass mail-outs by a government health agency were the most effective recruitment strategies. Close monitoring of recruitment outcomes and ongoing enhancement of recruitment activities played a central role in recruitment to this RCT. Trial registration ANZCTR, ID: ACTRN12612000287831. Registered on 12 March 2012. Electronic supplementary material The online version of this article (10.1186/s13063-019-3485-2) contains supplementary material, which is available to authorized users.

In men with obesity and IGT, serum testosterone (T) is inversely associated with incident T2D. Hypothesizing that T treatment prevents or reverses T2D beyond the effects of a lifestyle program alone, we conducted a multi-center, double-blinded placebo-controlled trial. Men (N=1007), aged 50-74 yrs., waist circumference (WC)>95cm, serum T≤14nmol/L (chemiluminescent assay), and IGT or newly diagnosed T2D, established by an OGTT, were randomized to receive, on a 1:1 basis, either IM T undecanoate (Reandron, Bayer) (1000mg/4ml) or vehicle (V) at baseline, 6 weeks and then 3-monthly for 2 yrs. All participants were enrolled in a lifestyle program (Weight Watchers® (WW)). Co-primary 2-yr outcomes: (1) OGTT 2-hr glucose ≥11 mmol/L: 55/443 (12.4%) in the T and 87/413 (21.1%) in V groups; RR (95% CI) 0.59 (0.43-0.80), P Disclosure G.A. Wittert: Research Support; Self; Bayer Inc., Lawley Pharmaceuticals, Lilly, Weight Watchers International, Inc. Speaker’s Bureau; Self; Besins. K.P. Robledo: None. M. Grossmann: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Novartis Pharmaceuticals Canada Inc., Otsuka Pharmaceutical Co., Ltd., Weight Watchers International, Inc. Speaker’s Bureau; Self; Besins Healthcare, Otsuka Pharmaceutical Co., Ltd. K. Bracken: None. B.B. Yeap: Advisory Panel; Self; Sanofi. Research Support; Self; Bayer AG, Lawley Pharmaceuticals. Speaker’s Bureau; Self; Besins, Sanofi. B.G.A. Stuckey: None. R.I. McLachlan: None. D.J. Handelsman: None. C. Allan: Advisory Panel; Self; Ferring Pharmaceuticals. Speaker’s Bureau; Self; Besins. W. Inder: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc. Speaker’s Bureau; Self; Amgen, Novo Nordisk Inc., Pfizer Inc. D. Jesudason: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. A.C. Keech: Advisory Panel; Self; Amgen, Kowa Research Institute, Inc. Consultant; Self; Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Amgen. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. M. Ng Tang Fui: None. M. Daniel: None. Funding National Health and Medical Council of Australia (1030123); Eli Lilly and Company; Bayer AG; Weight Watchers; University of Adelaide

Publisher's version (útgefin grein), Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health., This work has been supported by MRC grant MC_U106179472 (FD, KO, JRBP), Samuel Oschin Comprehensive Cancer Institute Developmental Funds, Center for Bioinformatics and Functional Genomics and Department of Biomedical Sciences Developmental Funds (MRJ), NCI P30CA177558 (CH), NCI UM1CA186107 (PK), European Regional Development Fund (Project No. 2014-2020.4.01.15-0012) and the European Union’s Horizon 2020 research and innovation program under grant agreements No 692065 (TL, RM, AS) and 692145 (RM), NICHD R01HD065029 (RS), Estonian Ministry of Education and Research (grant IUT34-16 to TL), NICHD R01HD057450 (MU), NICHD P50HD044405 (AD), NICHD R01HD057223 (AD), R01HD085227 (MGH, AD), deCode Genetics (GT, UT, KS, US), Raine Medical Research Foundation Priming Grant (BHM), SCGOPHCG RAC 2015-16/034 (SGW, BGAS), 2016-17/018 (BGAS), NIHR BRC, Wellcome Trust, MRC (TDS), Eris M. Field Chair in Diabetes Research (MOG), NIDDK P30 DK063491 (MOG), NIDDK U01DK094431, U01DK048381 (DE), NICHD U10HD38992 (RL), Estonian Ministry of Education and Research (grant IUT34-16), Enterprise Estonia (grant EU48695); the EU-FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP, grant SARM, EU324509 to AS), Wellcome (090532, 098381, 203141); European Commission (ENGAGE: HEALTH-F4-2007-201413 to MIM), MRC G0802782, MR/M012638/1 (SF), Li Ka Shing Foundation, WT-SSI/John Fell Funds, NIHR Biomedical Research Centre, Oxford, Widenlife and NICHD 5P50HD028138-27 (CML), NICHD R01HD065029, ADA 1-10-CT-57, Harvard Clinical and Translational Science Center, from the National Center for Research Resources 1UL1 RR025758 (CKW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: Exogenous androgen treatment suppresses the hypothalamo-pituitary testicular (HPT) axis causing reduced serum LH, FSH and testosterone (T). Recovery of male reproductive endocrine function in past androgen abusers takes 9-18 months with persistent mild lowering of serum T. The natural history of recovery of HPT axis following prolonged injectable testosterone undecanoate (TU) treatment at standard dose is not known. Therefore, the Runoff Study investigated the rate and extent of reproductive hormone recovery over 12 months following cessation of 2 years of TU treatment in the Testosterone for Diabetes Mellitus (T4DM) Study, while men remain blinded to treatment allocation. Methods: T4DM participants without pathological hypogonadism (n=1007) were randomised to TU or Placebo (P) injections every 3 months for 2 years with 303 subsequently volunteering to enter the Runoff study at 12 weeks after last injection. Before T4DM study unblinding, they provided blood samples and validated sexual function questionnaires (PDQ, IIEF-15) at entry (3 months after last injection), 6, 12, 18, 24, 40 and 52 weeks later. Serum steroid profile (T, DHT, E2, E1) was measured batchwise by LCMS and serum LH, FSH and SHBG by immunoassays. Results: Runoff study participants in both groups were similar and did not differ from all T4DM participants. As expected, at entry to Runoff serum T was higher in TU-treated men but at all timepoints from 12 weeks onwards serum T and SHBG remained consistently 11% and 13%, respectively, lower in TU-treated than in P-treated men. Similarly, at entry sexual function scores were higher in TU-treated men but subsequently no different from P-treated men. Serum LH and FSH recovered slowly with the median time to reach their own pre-treatment baseline of serum LH was 51.1 weeks [95% CI 50.4 – 53.0 weeks] and for serum FSH was 52.7 weeks [51.0 – 60.9 weeks]. Conclusion: After stopping 2 years of standard dose injectable TU treatment in men without pathological hypogonadism, recovery of testicular endocrine function is eventually complete but slow with serum gonadotropin recovery taking on 12 months since the last dose. Persistent mild, proportionate reduction in serum SHBG and T reflects lasting exogenous T effects on hepatic SHBG secretion rather than signifying androgen deficiency. This suggests that recovery from androgen-induced HPT axis suppression depends primarily on time since cessation rather than dose or duration of androgen exposure.

Background/aims: Participant recruitment to diabetes prevention randomised controlled trials is challenging and expensive. The T4DM study, a multicentre, Australia-based, Phase IIIb randomised controlled trial of testosterone to prevent Type 2 diabetes in men aged 50–74 years, faced the challenge of screening a large number of prospective participants at a small number of sites, with few staff, and a limited budget for screening activities. This article evaluates a high-volume, low-cost, semi-automated approach to screen and enrol T4DM study participants. Methods: We developed a sequential multi-step screening process: (1) web-based pre-screening, (2) laboratory screening through a network of third-party pathology centres, and (3) final on-site screening, using online data collection, computer-driven eligibility checking, and automated, email-based communication with prospective participants. Phone- and mail-based data collection and communication options were available to participants at their request. The screening process was administered by the central coordinating centre through a central data management system. Results: Screening activities required staffing of approximately 1.6 full-time equivalents over 4 years. Of 19,022 participants pre-screened, 13,108 attended a third-party pathology collection centre for laboratory screening, 1217 received final, on-site screening, and 1007 were randomised. In total, 95% of the participants opted for online pre-screening over phone-based pre-screening. Screening costs, including both direct and staffing costs, totalled AUD1,420,909 (AUD75 per subject screened and AUD1411 per randomised participant). Conclusion: A multi-step, semi-automated screening process with web-based pre-screening facilitated low-cost, high-volume participant enrolment to this large, multicentre randomised controlled trial. Centralisation and automation of screening activities resulted in substantial savings compared to previous, similar studies. Our screening approach could be adapted to other randomised controlled trial settings to minimise the cost of screening large numbers of participants.

INTRODUCTION Part 1 of this position statement dealt with the assessment of male hypogonadism, including the indications for testosterone therapy. This article, Part 2, focuses on treatment and therapeutic considerations for male hypogonadism and identifies key questions for future research. MAIN RECOMMENDATIONS Key points and recommendations are:Excess cardiovascular events have been reported in some but not all studies of older men without pathological hypogonadism who were given testosterone treatment. Additional studies are needed to clarify whether testosterone therapy influences cardiovascular risk.Testosterone is the native hormone that should be replaced in men being treated for pathological hypogonadism. Convenient and cost-effective treatment modalities include depot intramuscular injection and transdermal administration (gel, cream or liquid formulations).Monitoring of testosterone therapy is recommended for efficacy and safety, focusing on ameliorating symptoms, restoring virilisation, avoiding polycythaemia and maintaining or improving bone mineral density.Treatment aims to relieve an individual's symptoms and signs of androgen deficiency by administering standard doses and maintaining circulating testosterone levels within the reference interval for eugonadal men.Evaluation for cardiovascular disease and prostate cancer risks should be undertaken as appropriate for eugonadal men of similar age. Nevertheless, when there is a reasonable possibility of substantive pre-existing prostate disease, digital rectal examination and prostate-specific antigen testing should be performed before commencing testosterone treatment.Changes in management as result of the position statement: Treatment aims to relieve symptoms and signs of androgen deficiency, using convenient and effective formulations of testosterone. Therapy should be monitored for efficacy and safety.

Introduction This article, Part 1 of the Endocrine Society of Australia's position statement on male hypogonadism, focuses on assessment of male hypogonadism, including the indications for testosterone therapy. (Part 2 will deal with treatment and therapeutic considerations.) Main recommendations Key points and recommendations are:Pathological hypogonadism arises due to diseases of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) or testes (hypergonadotropic hypogonadism). It is a clinical diagnosis with a pathological basis, confirmed by hormone assays.Hormonal assessment is based on measurement of circulating testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Measurement of sex hormone-binding globulin levels can be informative, but use of calculated free testosterone is not recommended for clinical decision making.Testosterone replacement therapy is warranted in men with pathological hypogonadism, regardless of age.Currently, there are limited data from high-quality randomised controlled trials with clinically meaningful outcomes to justify testosterone treatment in older men, usually with chronic disease, who have low circulating testosterone levels but without hypothalamic, pituitary or testicular disease.Obesity, metabolic syndrome and type 2 diabetes are associated with lowering of circulating testosterone level, but without elevation of LH and FSH levels. Whether these are non-specific consequences of non-reproductive disorders or a correctable deficiency state is unknown, but clear evidence for efficacy and safety of testosterone therapy in this setting is lacking.Glucocorticoid and opioid use is associated with possibly reversible reductions in circulating testosterone level, without elevation of LH and FSH levels. Where continuation of glucocorticoid or opioid therapy is necessary, review by an endocrinologist may be warranted.Changes in management as result of the position statement: Men with pathological hypogonadism should be identified and considered for testosterone therapy, while further research is needed to clarify whether there is a role for testosterone in these other settings.

We audited the files of 114 postmenopausal women who had been treated with subcutaneous Estrapel (50mg oestradiol implants). Of the 92 women who received more than one implant, the median number of days between implants was 223.5 (range 49-875), with an estimated median time to return to baseline of 311days (range 108-1228). Although oestradiol implants can provide an excellent non-oral treatment option, their prolonged action makes patient selection important, as the implants cannot easily be removed. In women with an intact uterus, the continuation of progestin therapy after cessation of implant therapy is imperative.

Background: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). Aims: To determine in a multi-centre, double-blinded placebo-controlled randomized trial whether testosterone treatment combined with lifestyle intervention (Weight Watchers) relative to lifestyle intervention alone reduces T2DM incidence and improves glucose tolerance at 2 years. Study population: Overweight or obese men aged 50-74 years with a serum testosterone of ≤14 nmol/L and IGT or newly diagnosed T2DM established by an oral glucose tolerance test (OGTT). Setting, drug and protocol: Six Australian capital city-based tertiary care centres. Participants were randomized 1:1 and injected with testosterone undecanoate (1000 mg/4 mL) or vehicle (4 mL castor oil), at baseline, 6 weeks and 3-monthly thereafter. Primary endpoints: (a) Proportion of participants with 2-hour OGTT ≥11.1 mmol/L at 2 years, and (b) a difference at 2 years ≥0.6 mmol/L in the mean 2-hour OGTT glucose between treatments. Secondary endpoints: Fasting insulin, HbA1c, body composition, maximal handgrip strength; sexual function and lower urinary tract symptoms; serum sex steroids and sex hormone binding globulin; mood and psychosocial function; adherence to lifestyle intervention; and healthcare utilization and costs. Safety: Overseen by an Independent Data Safety Monitoring Committee. Haematocrit, lipids and prostate-specific antigen (PSA) are assessed 6-monthly and information relating to haematological, urological and cardiovascular adverse events from each clinic visit. Sub-studies: (a) Changes in bone density and micro-architecture, (b) motivation and behaviour, (c) telomere length, (d) extended treatment up to 4 years, and (e) hypothalamo-pituitary testicular axis recovery at treatment end.

Untreated vasomotor symptoms of the menopause can have a major impact on women at work. Recent recommendations advocate modification of the working environment, including adequate air-conditioning, to help relieve these symptoms. However, this may cause discomfort for work colleagues. We report the case of a 40-year-old woman with cold urticaria. Cold urticaria is a serious, potentially life-threatening condition. Our patient's symptoms were exacerbated when her postmenopausal work colleagues turned the air-conditioner temperature down to relieve their vasomotor symptoms.

This multicentre randomised double-blind placebo-controlled clinical trial assessed the efficacy and safety of a methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib, in individuals with obesity (BMI ≥30 kg/m2) and type 2 diabetes (HbA1c 53–97 mmol/mol [7–11%] and fasting glucose

Aim: To assess the efficacy, safety and tolerability of beloranib treatment for obesity. Methods: This phase II, double-blind, randomized study investigated the effects of beloranib suspension (0.6, 1.2 and 2.4mg) or placebo, administered subcutaneously, for 12weeks in 147 participants (primarily white women) with obesity. No diet or exercise advice was administered. Results: At week 12, beloranib resulted in dose-dependent progressive weight loss of -5.5±0.5, -6.9±0.6 and -10.9±1.1kg for the 0.6, 1.2 and 2.4mg beloranib doses, respectively, compared with -0.4±0.4kg with placebo (all p

In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses.Women (n = 3,657) and men (n = 6,138) with type 2 diabetes not using statins were assigned fenofibrate (200 mg/day) or placebo for 5 years. Effects on lipoproteins and total cardiovascular events were evaluated by sex.Baseline total, LDL-, HDL- and non-HDL cholesterol and apolipoproteins A-I and B differed between sexes, and these and triacylglycerol levels improved with fenofibrate in both sexes (all p 0.001). Fenofibrate reduced total, LDL- and non-HDL cholesterol and apolipoprotein B more in women (all p 0.001), independent of menopausal status and statin uptake. Adjusted for covariates, fenofibrate reduced total cardiovascular outcomes (cardiovascular death, fatal and non-fatal stroke and carotid and coronary revascularisation) by 30% in women (95% CI 8%, 46%; p = 0.008) and 13% in men (95% CI -1%, 24%; p = 0.07) with no treatment-by-sex interaction (p 0.1). In patients with high triacylglycerol levels and low HDL-cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% (95% CI -7%, 54%) in women and 24% (95% CI 2%, 42%) in men, with no treatment-by-sex interaction (p 0.1).Fenofibrate improved the lipoprotein profile more in women than men. Cardiovascular event reductions with fenofibrate were consistently similar in women and men, both overall and among those with low HDL-cholesterol and high triacylglycerol levels. These data provide reassurance about fenofibrate efficacy in women and men. Both sexes with type 2 diabetes should be considered for fenofibrate therapy for cardioprotection.

Context Polycystic ovary syndrome (PCOS) is a prevalent condition with heterogeneity of clinical features and cardiovascular risk factors that implies multiple aetiological factors and possible outcomes. Objective To reduce a set of correlated variables to a smaller number of uncorrelated and interpretable factors that may delineate subgroups within PCOS or suggest pathogenetic mechanisms. Materials and methods We used principal component analysis (PCA) to examine the endocrine and cardiometabolic variables associated with PCOS defined by the National Institutes of Health (NIH) criteria. Data were retrieved from the database of a single clinical endocrinologist. We included women with PCOS (N = 378) who were not taking the oral contraceptive pill or other sex hormones, lipid lowering medication, metformin or other medication that could influence the variables of interest. PCA was performed retaining those factors with eigenvalues of at least 1.0. Varimax rotation was used to produce interpretable factors. Results We identified three principal components. In component 1, the dominant variables were homeostatic model assessment (HOMA) index, body mass index (BMI), high density lipoprotein (HDL) cholesterol and sex hormone binding globulin (SHBG); in component 2, systolic blood pressure, low density lipoprotein (LDL) cholesterol and triglycerides; in component 3, total testosterone and LH/FSH ratio. These components explained 37%, 13% and 11% of the variance in the PCOS cohort respectively. Conclusions Multiple correlated variables from patients with PCOS can be reduced to three uncorrelated components characterised by insulin resistance, dyslipidaemia/hypertension or hyperandrogenaemia. Clustering of risk factors is consistent with different pathogenetic pathways within PCOS and/or differing cardiometabolic outcomes.

Objective To examine the prevalence of a history of polycystic ovary syndrome (PCOS) in women with type 2 diabetes (DM2) and to compare metabolic and reproductive outcomes between women with and without PCOS. Design Cross-sectional study. Setting Tertiary hospital. Patient(s) Female inpatients age 18–75 years with DM2. Intervention(s) A face-to-face questionnaire was administered. Main Outcome Measure(s) Age at diagnosis of diabetes, history of gestational diabetes, family history of diabetes, and reproductive history, fertility history, number of miscarriages, and morbidity in pregnancy. Result(s) One hundred seventy-one inpatients with DM2 participated. The prevalence of a history of PCOS was 37%. Women with PCOS had an earlier mean age of diagnosis of DM2 (44.2 vs. 48.8 years), higher recalled peak body mass index (BMI; 43.1 kg/m 2 vs. 36.8 kg/m 2 ), higher rate of gestational diabetes (28% vs. 18%), and higher rate of hypertension in pregnancy (40% vs. 22%). Women with PCOS were less likely to have a family history of DM2 than those without PCOS (45% vs. 67%). Conclusion(s) A history of PCOS in women with DM2 is associated with earlier onset of DM2, higher BMI, and a more severe phenotype. Since PCOS subjects were less likely to have a family history of DM2, lack of a family history of DM2 in women with PCOS is not reassuring for DM2 risk. We recommend identifying PCOS in early life and intervening to reduce the risk of diabetes and its comorbidities and suboptimal reproductive outcomes.

Introduction Obesity is associated with reduced testosterone and worsened erectile and sexual function in men. Weight loss improves these outcomes. High protein diets potentially offer anthropometric and metabolic benefits, but their effects on reproductive and sexual outcomes is not known. Aim To examine the long-term effects of weight loss with a higher protein or carbohydrate diet on testosterone, sex hormone binding globulin, erectile dysfunction, lower urinary tract symptoms and sexual desire in overweight and obese men. Methods One-hundred and eighteen overweight or obese men (body mass index 27–40 kg/m2, age 20–65 years) were randomly assigned to an energy restricted higher protein low fat (35% protein, 40% carbohydrate, 25% fat; n = 57) or higher carbohydrate low fat diet (17% protein, 58% carbohydrate, 25% fat, n = 61) diet for 52 weeks (12 weeks weight loss, 40 weeks weight maintenance). Primary outcomes were serum total testosterone, sex hormone binding globulin and calculated free testosterone. Secondary outcomes were erectile function as assessed by the International Index of Erectile Function (IIEF) (total score and erectile function domain), lower urinary tract symptoms and sexual desire. Results Total testosterone, sex hormone binding globulin and free testosterone increased (P

Introduction We previously described dynamic, noncontrast magnetic resonance imaging (MRI) of the female genitalia as a reproducible, nonintrusive, objective means of quantifying sexual arousal response in women without sexual difficulties. These studies showed an increase in clitoral engorgement ranging from 50 to 300% in healthy women during sexual arousal. Aim This study sought to evaluate the genital arousal response in women with female sexual arousal disorder (FSAD) after administration of sildenafil and placebo. We performed a multicenter, double‐blind, placebo‐controlled, cross‐over study to assess the clitoral engorgement response using dynamic MRI in women with FSAD after administering sildenafil and placebo followed by audiovisual sexual stimulation (AVSS). Methods Nineteen premenopausal women with FSAD underwent two MRI sessions. Subjects were randomized to receive either (i) sildenafil 100 mg during the first session followed by placebo during the second session, or (ii) placebo followed by sildenafil. During each session, baseline MR images were obtained while subjects viewed a neutral video. Subjects then ingested sildenafil or placebo. After 30 minutes, a series of MRIs were obtained at 3‐minute intervals for 10 time points while subjects viewed AVSS. Main Outcome Measures A positive sexual arousal response was achieved if clitoral volume increased ≥50% from baseline. Results Thirteen of 19 (68%) subjects achieved a ≥50% increase in clitoral engorgement from baseline when administered sildenafil or placebo 30 minutes after dose administration. At 60 minutes after administration, 17/19 (89%) subjects receiving sildenafil and 16/19 (84%) subjects receiving placebo had responded ( P value 0.3173). Conclusions Sildenafil did not augment the genital response in women with FSAD. Secondarily, a majority of women in this study did not have impaired clitoral engorgement as measured by MRI, suggesting that FSAD is not predominantly a disorder of genital engorgement. Leddy LS, Yang CC, Stuckey BG, Sudworth M, Haughie S, Sultana S, and Maravilla KR. Influence of sildenafil on genital engorgement in women with female sexual arousal disorder. J Sex Med **;**:**–**.

Serum total calcium (tCa) is routinely measured for diagnosing calcium disorders but may not reflect levels of biologically active ionized calcium (iCa) in disease or detect all cases of primary hyperparathyroidism.We investigated the utility of measuring iCa and tCa for diagnosing primary hyperparathyroidism.This was an observational, retrospective, cross-sectional study.We studied a biochemistry cohort of consecutive ambulatory outpatients with suspected bone or calcium metabolism disorders referred for calcium metabolism biochemistry panels and a surgical cohort of consecutive tertiary hospital patients whose parathyroid specimens were submitted to a single center, and consecutive parathyroidectomy patients of a single surgeon with specimens submitted to a different center.In 5490 biochemistry cohort patients, discordance between iCa and tCa in classifying calcium status occurred in 12.6% of cases overall but was worse in hypercalcemic (whether defined by tCa and/or iCa) cases (49%) and hypocalcemic cases (92%). Reliance on tCa alone would miss 45% with ionized hypercalcemia. In 315 biochemistry cohort cases with PTH-dependent hypercalcemia, 130 (41%) had isolated ionized hypercalcemia at diagnosis. In 143 patients with histologically proven parathyroid disease, 24% had isolated ionized hypercalcemia at diagnosis. These patients were younger (P = 0.022) with milder ionized hypercalcemia and better renal function (both P ≤ 0.001) than patients presenting with concurrently elevated iCa and tCa.In abnormal calcium states, tCa frequently disagrees with iCa in classifying calcium status. Histologically proven parathyroid disease can present with isolated ionized hypercalcemia. Measurement of iCa is required to accurately assess calcium status and improve diagnostic accuracy.

In this cross-sectional study, we investigated the prevalence of hypertriglyceridaemia (hyperTG) in 182 statin-treated type 2 diabetic (T2DM) patients. Predictors of hyperTG (≥2.3mmol/L) were investigated using logistic regression. The prevalence of hyperTG was 20.9%, with lower prevalence in patients with low-density lipoprotein (LDL)-cholesterol

Summary Background Postpartum thyroid dysfunction (PPTD) is characterized by an early hyperthyroid phase followed, with peak prevalence at 6 months, by a hypothyroid phase which carries a risk of long-term hypothyroidism. Iodine has a major effect on thyroid function. Western Australia has previously been shown to be iodine replete. Objective To examine the iodine status of women with and without PPTD and the relationship of iodine status postpartum with long-term hypothyroidism. Design Case–control with follow-up. Patients A total of 149 women at 6 months postpartum (74 PPTD, 75 controls) with 98 (46 PPTD, 52 controls) followed up at 12 years. Measurements Urinary iodine concentration (UIC) and thyroid function at 6 months postpartum; thyroid function at 12-year follow-up. Results At 6 months postpartum, median UIC (quartiles) for observed TSH ranges were: for TSH 4·0 mU/l 85·0 μg/l (40·0, 141·5), P = 0·018. The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2·54, (95%CI: 1·47, 4·35), and with UIC

Background The long-term risk of hypothyroidism following postpartum thyroid dysfunction (PPTD) is uncertain. Most previous studies have been small, short-term or have lacked a control group. Objective To ascertain the long-term risk of hypothyroidism in women following PPTD. Design and participants A 12-year longitudinal study of 409 women (including 71 with PPTD) who previously participated in a PPTD prevalence study. Measurements The primary outcome measure was hypothyroidism (defined as TSH greater than 4 mU/l or on thyroxine replacement) at follow-up. Outcomes in women with and without PPTD were compared by logistic regression. Receiver operating characteristic analysis was used to determine the optimal cut-off for baseline TSH as a predictor of hypothyroidism in the cohort. Results At follow-up, hypothyroidism was present in 27 of 71 women who had PPTD at baseline (38%) and 14 of 338 women without PPTD (4%). From multivariate analysis, odds ratios (with 95% confidence intervals) for hypothyroidism were – 4·8 (1·6, 14·1) for PPTD; 8·2 (2·8, 24·6) for positive thyroid peroxidase antibodies (TPOAb); 9·7 (2·6, 37·0) for the hypothyroid phase of PPTD and 51·4 (19·2, 137·5) for hypothyroid PPTD with positive TPOAb. A baseline TSH above 2·6 mU/l was the optimal cut-off for predicting hypothyroidism (sensitivity 76%, specificity 86%). Conclusions PPTD is a strong predictor of hypothyroidism in the long-term. Women who present with postpartum hypothyroidism or have positive TPOAb are at particularly high risk, suggesting that close long-term follow-up is advisable if thyroxine replacement is not instituted at an early stage.

There is an association between nonalcoholic fatty liver disease (NAFLD) and the polycystic ovary syndrome (PCOS). Marine-derived omega-3 fatty acids have favorable effects on cardiovascular risk and could reduce liver fat in NAFLD.The primary aim of this study was to examine the effects of omega-3 fatty acids on liver fat in PCOS. The secondary aim was to assess their effects on traditional cardiovascular risk factors.We conducted a randomized, crossover study at a tertiary cardiovascular research center.Twenty-five women with PCOS (mean age, 32.7 yr; mean body mass index, 34.8 kg/m(2)) participated in the study.We compared 4g/d of omega-3 fatty acids with placebo over 8 wk.The primary outcome measure was hepatic fat content quantified using proton magnetic resonance spectroscopy. Secondary outcome measures included fasting lipids and blood pressure.Omega-3 fatty acids significantly decreased liver fat content compared with placebo [10.2 (1.1) vs. 8.4 (0.9)%; P = 0.022]. There was also a reduction in triglycerides [1.19 (1.03-1.47) vs. 1.02 (0.93-1.18) mmol/liter; P = 0.002], systolic blood pressure [124.1 (12.1) vs. 122.3 (14.5) mm Hg; P = 0.018], and diastolic blood pressure [73.2 (8.4) vs. 69.7 (8.3) mm Hg; P = 0.005] with omega-3 fatty acids compared with placebo. Omega-3 fatty acids particularly decreased hepatic fat in women with hepatic steatosis, defined as liver fat percentage greater than 5% [18.2 (11.1) vs. 14.8 (9.3)%; P = 0.03].Omega-3 fatty acid supplementation has a beneficial effect on liver fat content and other cardiovascular risk factors in women with PCOS, including those with hepatic steatosis. Whether this translates into a reduction in cardiometabolic events warrants further study.

Introduction Alcohol consumption is a contentious social topic and is often assumed to have deleterious effects on sexual performance. There is a lack of consensus on whether alcohol consumption may in fact be beneficial to erectile function. Aim We examined the data from a population-based cross-sectional study of men's health to assess the association between usual alcohol consumption and erectile dysfunction (ED). Method Reply-paid questionnaires were posted to a randomly selected age-stratified male population sample obtained from the Western Australian (WA) Electoral Roll. Main Outcome Measures The survey questionnaire included sociodemographic details, self-reported clinical information, and drinking habits. The 5-item International Index of Erectile Function (IIEF-5) was used to assess erectile function. Results Most (87%) participants were current alcohol drinkers, with binge drinking, as defined by the Australian National Health and Medical Research Council (NHMRC), reported by 20% of drinkers. Compared with never-drinkers, the age-adjusted odds of ED were lower among current, weekend, and binge drinkers and higher among ex-drinkers. Among current drinkers, the odds were lowest for consumption within the NHMRC guidelines of between 1 and 20 standard drinks a week. On further adjustment for cardiovascular disease (CVD) or for cigarette smoking, age-adjusted odds of ED were reduced by 25–30% among alcohol drinkers. Conclusions Our findings suggest a modest negative association between alcohol consumption and ED and confounding of the association by CVD and cigarette smoking. The Western Australia Men's Health Study certainly provides no justification for advising men with ED whose drinking habits are consistent with NHMRC guidelines that they should cease or reduce their consumption of alcohol. Chew K-K, Bremner A, Stuckey B, Earle C, and Jamrozik K. Alcohol consumption and male erectile dysfunction: An unfounded reputation for risk? J Sex Med 2009;6:1386–1394.

We report the findings pertinent to the ageing and elderly participants of a population-based study of erectile dysfunction (ED).We examined the sociodemographic characteristics, self-reported morbidities and responses to the 5-item International Index of Erectile Function (IIEF-5) of participants agedor = 65 years andor = 80 years.Most (73%) participants were married or had partners. Among the participants agedor = 65 years, the prevalence of ED (IIEF-5 scores22) was 67% and of severe ED (IIEF-5 scores8) 48%. About 32% were sexually active, and 11% had regular sexual intercourse. Cardiovascular disease (CVD) was reported in 37% and diabetes mellitus (DM) in 13%, with odds of ED at 3.91 and 4.68, respectively. Among those agedor = 80 years, the prevalence of ED was 68% and of severe ED 57%. About 12% were sexually active, and 3% had regular sexual intercourse. CVD was reported in 44% and DM in 11%, with corresponding odds of ED at 2.55 and 2.90.Most ageing and elderly men are in a relationship and many are sexually active. ED is prevalent and severe. Morbidities are common and significantly associated with ED, impairing the sex lives of affected men.

Introduction Sexual function in women in the reproductive age years is under psychological, sociocultural, and relationship influences, as well as the influence of sex hormones. Aim To examine the data relating to sexual function in women in the reproductive age group, particularly the influence of sex hormones. To examine, in particular, the influence of the menstrual cycle, pregnancy, the oral contraceptive pill and endogenous and exogenous testosterone. Methods Review of the literature on female sexual function, confining the search to the reproductive age range. Results Population studies of sexual function identify sexual disinterest as being the most common sexual complaint in premenopausal women. Most studies of menstrual cyclicity identify a periovulatory increase in sexual desire or activity. All prospective studies of sexuality in pregnancy document a decline in sexual function with progression of pregnancy. Studies of the influence of the oral contraceptive pill on sexual function are contradictory with most prospective controlled studies showing no deleterious effect. Studies of the influence of endogenous androgens on sexuality are also contradictory with one large cross‐sectional study showing no correlation, but some case‐controlled studies show low androgens in women with sexual dysfunction. Studies of testosterone therapy in premenopausal women are ambiguous, with no clear dose‐response effect. Conclusion Sexual disinterest is prevalent in premenopausal woman despite being hormone replete. The assessment of androgen contribution is hampered by the unreliability of the testosterone assay in the female range. Large cross‐sectional and longitudinal studies have not identified a correlation between testosterone and sexual function in women. Sexual dysfunction in the premenopausal age range is common. Sex hormones have a modifying effect on sexual function but social influences and learned responses are as important. The role of testosterone requires further study. Stuckey BGA. Female sexual function and dysfunction in the reproductive years: The influence of endogenous and exogenous sex hormones. J Sex Med 2008;5:2282–2290.

OBJECTIVE—To investigate the effects of fenofibrate and coenzyme Q10 (CoQ) on diastolic function, ambulatory blood pressure (ABP), and heart rate (HR) in type 2 diabetic subjects with left ventricular diastolic dysfunction (LVDD). RESEARCH DESIGN AND METHODS—We randomized, double-blind, 74 subjects to fenofibrate 160 mg daily, CoQ 200 mg daily, fenofibrate 160 mg plus CoQ 200 mg daily, or matching placebo for 6 months. Echocardiography (including tissue Doppler imaging) and 24-h ABP and HR monitoring were performed pre- and postintervention. RESULTS—Neither fenofibrate nor CoQ, alone or in combination, altered early diastolic mitral annular myocardial relaxation velocity (E′), early-to-late mitral inflow velocity ratio (E/A), deceleration time, isovolumic relaxation time, or the ratio of early mitral flow velocity to early diastolic mitral annular myocardial relaxation velocity (E/E′) compared with placebo (P > 0.05). Fenofibrate and CoQ interactively (P = 0.001) lowered 24-h systolic blood pressure (−3.4 ± 0.09 mmHg, P = 0.010), with a prominent nocturnal effect (−5.7 ± 1.5 mmHg, P = 0.006). Fenofibrate (−1.3 ± 0.5 mmHg, P = 0.013) and CoQ (−2.2 ± 0.5 mmHg, P < 0.001) independently lowered 24-h diastolic blood pressure. Fenofibrate reduced 24-h HR (−3.3 ± 0.5 beats/min, P < 0.001), but CoQ had no effect on HR. CONCLUSIONS—In type 2 diabetic subjects with LVDD, neither fenofibrate nor CoQ, alone or in combination, improved diastolic function significantly. However, fenofibrate and CoQ independently and interactively lowered 24-h blood pressure, and fenofibrate alone reduced 24-h HR.

Introduction Persistent sexual arousal is defined as an intrusive and unwanted genital arousal unrelated to sexual desire and typically unrelieved by one or more orgasms.

Introduction This is a report of a population-based cross-sectional observational study in Western Australia (WA) on male erectile dysfunction (ED). Aim To assess the prevalence of ED in WA and to examine its associated sociodemographic factors. Method Postal questionnaires were sent to randomly selected age-stratified male population samples obtained from the WA Electoral Roll. Main Outcome Measures In addition to items covering sociodemographic and clinical information, the Australian Standard Classification of Occupations (ASCO), the Socioeconomic Index for Area (SEIFA), and the 5-item International Index of Erectile Function (IIEF-5) were used. Results One thousand seven hundred seventy (41.9%) of 4,228 questionnaires were returned. One thousand five hundred eighty (89.3%) were completed questionnaires from men aged 20.1 to 99.6 years (mean 57.9, median 59.1, standard deviation 18.5). The prevalences of any ED and of severe ED among adult males in WA, adjusted for age distribution, were 25.1 and 8.5%, respectively. Standardized to World Health Organization (WHO) World Standard Population, the corresponding prevalences were 23.4 and 7.4%. Prevalence, as well as severity, of ED increased with age. Thirty-eight percent of the participants who were married or had partners experienced ED (severe ED 19.1%). The prevalence of ED was not significantly different between “white-collar” and “blue-collar” workers. Despite the great majority of the affected participants having experienced ED for >1 year, only 14.1% reported having ever received any treatment for ED. Conclusions The study has provided population-based epidemiological data on ED in Western Australian men covering a wide range of ages. The finding that ED is age related, highly prevalent, and grossly underdiagnosed and undertreated is pertinent to global population aging and a rapidly aging Australian population. To facilitate comparisons across populations with different age distributions, all future population-based studies on ED should be standardized to WHO World Standard Population. Chew K-K, Stuckey B, Bremner A, Earle C, and Jamrozik K. Male Erectile Dysfunction: Its Prevalence in Western Australia and Associated Sociodemographic Factors.

To determine whether idiopathic erectile dysfunction, in the absence of overt cardiovascular disease or cardiovascular risk factors, is associated with vascular or autonomic dysfunction.We studied 49 men with ED (without known cardiovascular risk factors or disease) and 50 age-matched controls, aged 40-70 years. Macrovascular endothelial function was examined by brachial artery ultrasonography and microvascular function by venous occlusion plethysmography. Blood pressure measurement and electrocardiography were performed lying and standing, and the 30:15 RR ratio calculated.Body mass index, testosterone, fasting lipids and glucose did not differ significantly between groups. Standing pulse pressure was higher (50+/-1mm Hg versus 43+/-2mm Hg, p0.004) and 30:15 RR ratio lower (0.97+/-0.01 versus 1.01+/-0.01, p0.02) in the ED group. Flow-mediated dilatation of the brachial artery was not significantly different between groups. Flow debt repayment during forearm reactive hyperaemia was lower in the ED group (7.2+/-0.7 ml versus 9.5+/-0.8 ml per 100ml, p0.02) than in controls.Men with idiopathic ED have evidence of endothelial dysfunction in forearm resistance vessels, increased pulse pressure and impaired heart rate variability. This supports the concept that erectile dysfunction is a predictor of cardiovascular dysfunction and a precursor of clinical cardiovascular disease.

Summary Objective Polycystic ovary syndrome (PCOS) has clinical features and implications for long-term health that may lead to decreased quality of life (QoL) and psychological morbidity. We studied QoL in women with PCOS, compared the findings with population norms and assessed whether they correlated with reported quality of patient information received. Design Cross-sectional study. Patients Women with PCOS by National Institutes of Health (NIH) criteria, diagnosis confirmed by one endocrinologist. Measurements Four questionnaires were mailed: the Short Form-36 (SF-36), the Quality-of-Life Questionnaire for Women with Polycystic Ovary Syndrome (PCOSQ), the General Health Questionnaire-28 (GHQ-28) and an assessment of information quality and sources, the Patient Information Questionnaire (PIQ). Results Questionnaires were sent to 443 women with PCOS from one endocrinologist's database; 203 women aged 15–65 years agreed to participate. To compare with Australian population norms, data from those women aged 18–44 years (n = 173) were used. Of these, 64% were obese, 18% overweight and 18% of normal weight. The demographics, socioeconomic status and untreated biochemistry of the responders and the total patient group were not significantly different. SF-36 scores were significantly lower than the age- and sex-matched Australian population (P

Objective: To investigate polymorphisms in androgen metabolism regulators that are implicated in the etiology of polycystic ovary syndrome (PCOS) in vitro; to investigate HSD17B6 and GATA6 to determine whether these genes are associated with susceptibility to PCOS or key phenotypic features of patients with PCOS. Design: Case-control association study. Setting: Participants with PCOS were recruited from a clinical-practice database, and controls, from the general community. Patient(s): One hundred seventy-three patients with PCOS and who were of Caucasian descent and conformed to the National Institutes of Health (NIH) diagnostic criteria; 107 normally ovulating women of Caucasian descent from the general community. Intervention(s): Drawing of blood for DNA extraction. Main Outcome Measure(s): Frequency of HSD17B6 and GATA6 polymorphisms in cases and controls. Association of single-nucleotide polymorphisms from HSD17B6 in subjects with PCOS with key phenotypes of PCOS: androgen status, insulin resistance, and body mass index. Result(s): Allele distribution for the single-nucleotide polymorphism rs898611 in HSD17B6 was significantly different between PCOS and control subjects (P=.03). Presence of the polymorphic allele was associated with reduced fasting glucose-insulin ratio (P=.02) and increased homeostasis model assessment (P

The new millennium has brought intense focus of interest on the risk of cardiovascular disease in women. The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women characterised by hyperandrogenism and oligomenorrhoea. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Echocardiography, imaging of coronary and carotid arteries, and assessments of both endothelial function and arterial stiffness have recently been employed to address this question. These studies have collectively demonstrated both structural and functional abnormalities of the cardiovascular system in PCOS. These alterations, however, appear to be related to the presence of individual cardiovascular risk factors, particularly insulin resistance, rather than to the presence of PCOS and hyperandrogenaemia per se. However, given the inferential nature of the evidence to date, more rigorous cohort studies of long-term cardiovascular outcomes and clinical trials of risk factor modification are required in women with PCOS.

Summary Increasing numbers of women have menopausal symptoms after treatment for breast cancer. These symptoms can result directly from cancer treatments (such as oophorectomy, ovarian suppression, chemotherapy-induced ovarian failure, and antioestrogens), as a spontaneous event, or after discontinuation of hormone-replacement therapy. The onset of menopausal symptoms after treatment for breast cancer can have a long-lasting effect on quality of life, body image, sexual function, and self esteem. Hormone-replacement therapy that contains oestrogen is the most effective treatment for menopausal symptoms in healthy women. However, evidence from one randomised controlled trial suggests that use of hormone replacement therapy after breast cancer raises the risk of recurrence and of new primary breast cancer. As the incidence of breast cancer increases and survival continues to improve, the number of women with menopausal symptoms will probably rise. Safe and effective non-hormonal treatments for severe menopausal symptoms after breast cancer are urgently needed. Few studies have addressed the management of menopausal symptoms after breast cancer, and the quality of studies is generally poor. Progestagens, and selective inhibitors of serotonin and norepinephrine reuptake seem to offer reasonable symptom palliation, but the long-term effectiveness and safety of these preparations is not known. We propose that the management of menopausal symptoms in patients with a history of cancer requires a patient-centred, but multidisciplinary, approach.