David J Handelsman's research while affiliated with State Library of New South Wales and other places

Publications (763)

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The gut microbiome has been implicated in polycystic ovary syndrome (PCOS) pathophysiology. PCOS is a disorder with reproductive, endocrine and metabolic irregularities, and several studies report that PCOS is associated with a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, as alterations in m...
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Polycystic ovary syndrome (PCOS) is a common, multifactorial disorder characterized by endocrine, reproductive and metabolic dysfunction. As the etiology of PCOS is unknown, there is no cure and symptom-oriented treatments are suboptimal. Hyperandrogenism is a key diagnostic trait and evidence suggests androgen receptor (AR) mediated actions are cr...
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Context Clinical evaluations that require excluding androgen abuse, a secretive, illicit activity, rely on the drug history but its veracity for androgen abuse has neither been verified nor has any objective corroborating laboratory test been validated. Objective In a high-risk population, to (a) validate the drug history of androgen abuse objecti...
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The high sensitivity of antidoping detection tests creates the possibility of inadvertent doping due to an athlete’s unknowing ingestion of contaminated environmental sources such as dietary supplements, food, or drinks. Recently athletes denying use of a prohibited substance have claimed that the positive antidoping tests was due to exchange of bo...
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Objective: In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking. This study aimed to determine the effects of E2 on bone health in men in the absence of endogenous T. Design: 6-month randomised, placebo-controlled trial with the hypothesis that E2 would slow...
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Introduction: This study aimed to assess the extent to which a single item of self-reported hearing difficulties is associated with future risk of falling among community-dwelling older adults. Methods: We used data from two Australian population-based cohorts: three waves from the PATH Through Life study (PATH; n = 2,048, 51% men, age 66.5 ± 1....
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Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti‐androgen drug, flutamide accel...
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Objectives: The aims of this study were to assess oral health-related quality of life (OHRQoL) in a cohort of older Australian men and explore the association between their general health conditions, socio-demographic factors and OHRQoL. Methods: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representa...
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Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability. It is a major transformational period of life, whose timing is strongly affected by genetic makeup of the individual, along with various internal and external factors. Although the exact mechanism for initiation of the cascade of molecu...
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Abuse of androgens and erythropoietin make hormonal doping the most effective and frequent class of ergogenic substances prohibited in elite sports by the World Anti-Doping Agency (WADA). At present, thyroid hormone (TH) abuse is not prohibited but its prevalence among elite athletes and non-prohibited status remains controversial. A corollary of p...
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Importance: Among older adults, there is limited and inconsistent evidence on the association between socioeconomic position (SEP) and elective and nonelective hospitalization. Objective: To evaluate the association between SEP and all-cause and cause-specific elective and nonelective hospitalization and hospital length of stay among older men....
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Background: Past research on social support and dental visits in older people has been limited by cross-sectional design, limited social support dimensions, and non-representative samples. Methods: Data came from men with natural teeth completing Waves 3 and 4 of the Concord Health and Ageing in Men Project (CHAMP) in Sydney, Australia. The rela...
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Background Nutritional intake could influence the development of frailty. The aim was to evaluate the associations between dietary iron intakes and changes in dietary iron intakes with frailty. Methods Cross-sectional analyses involved 785 men with Fried frailty phenotype (FP) and 758 men with Rockwood frailty index (FI) data aged 75 years and ove...
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Background Ageing and multimorbidity are associated with inflammation. Polypharmacy is common in older people with multimorbidity. Given the potential for interactions between polypharmacy and inflammation, the relationship between inflammation and polypharmacy were studied in older adults with multimorbidity and in healthy ageing mice. Methods A...
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Context: The time course of male reproductive hormone recovery after stopping injectable testosterone undecanoate (TU) treatment is not known. Objective: To investigate rate, extent, and determinants of reproductive hormone recovery over 12 months after stopping TU injections. Methods: Men (n=303) with glucose intolerance but without pathologic hyp...
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Polycystic ovary syndrome (PCOS) is associated with androgen excess and, frequently, hyperactive pulsatile luteinizing hormone (LH) secretion. While PCOS origins are unclear, evidence from pre‐clinical models implicate androgen signalling in the brain in the development of PCOS pathophysiology. Chronic exposure of female mice to dihydrotestosterone...
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Objective To determine the semen quality and reproductive hormones of men conceived by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) compared with men conceived without assisted reproductive technology (ART). Design Cohort study. Setting IVF centers in Victoria and the Western Australian Raine Study. Patient(s) Men con...
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Background Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and ris...
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Objective: Roles for estradiol in modulating cognition in men remain uncertain. We assessed the isolated effects of estradiol on cognition in men in the absence of testosterone. Design: Randomised trial of transdermal estradiol 0.9mg daily, or matched placebo, for 6 months, hypothesizing that estradiol would improve verbal learning, verbal memor...
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BACKGROUND Anemia is associated with increased risk of all-cause mortality in older populations. However, the relationship between hemoglobin and major adverse cardiovascular events (MACE), and whether this is modulated by frailty, is unclear. METHODS CHAMP (Concord-Health-and-Ageing-in-Men-Project) is a prospective study of community-dwelling men...
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Introduction: The association of testosterone concentrations with dementia risk remains uncertain. We examined associations of serum testosterone and sex hormone-binding globulin (SHBG) with incidence of dementia and Alzheimer's disease. Methods: Serum total testosterone and SHBG were measured by immunoassay. The incidence of dementia and Alzhei...
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Recent studies have highlighted the potential role of 11oxygenated (keto or hydroxy) androgens in human reproductive function with 11keto androgens circulating at concentrations comparable with testosterone in women and children. However, the intrinsic androgenic bioactivities of 11 keto and hydroxy androgens are not fully characterized. We therefo...
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Background: The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria. Objective: To analyze associations of serum total testosterone an...
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To compare the Australian Dietary Guideline Index (DGI-2013) and the Pyramid-based Mediterranean Diet Score (pyrMDS) as measures of diet quality in an ethnically diverse group of older men. Seven hundred and ninety-four older men aged ≥75 participated in wave 3 (2012–2013) of the Concord Health and Ageing in Men Project. Dietary intake was assessed...
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The ready detectability of synthetic androgens by mass spectrometry (MS)‐based antidoping tests has reoriented androgen doping to using testosterone (T) which must be distinguished from its endogenous counterpart making detection of exogenous T harder. We investigated urine and serum steroid and hematological profiling individually and combined to...
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Background The association between dietary protein intake and the risk of mortality is still controversial. The present study aimed to examine the associations between dietary total, animal and plant protein intake and all-cause and cause-specific mortality. Methods Community-dwelling men aged ≥ 70 years were recruited from local government areas...
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Background: The association between dietary protein intake and the risk of mortality is still controversial. The present study aimed to examine the associations between dietary total, animal and plant protein intake and all‐cause and cause‐specific mortality. Methods: Community‐dwelling men aged ≥ 70 years were recruited from local government area...
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Ovarian hyperthecosis (OHT), severe hyperandrogenism after menopause in the absence of ovarian or adrenal tumors, is usually treated by surgical excision. We report a 58-year-old woman presenting with severe hyperandrogenism (serum testosterone 15.7-31.0 nmol/L, normal female <1.8 nmol/L) with menopausal gonadotropins and virilization but no adrena...
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Background and Aims Mediterranean dietary patterns may exert favourable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet as well as its components, with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men. Methods Seven hundred nin...
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Objective: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatisation to estradiol. However, no controlled study has assessed the effects of estradiol in the absence of testosterone. Design: 6-month randomised, placebo-controlled trial with the hypothesis that men randomised to estradiol would r...
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Context Vitamin D status is conventionally defined by measurement of unconjugated circulating 25-hydroxyvitamin D (25OHD), but it remains uncertain whether this isolated analysis gives sufficient weight to vitamin D’s diverse metabolic pathways and bioactivity. Emerging evidence has shown that phase II endocrine metabolites are important excretory...
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Objective Inadequate nutrient intakes have been linked with poor dentition in older adults. The aim of this study was to investigate the associations between composition of Functional Tooth Units (FTUs) and nutrient intakes in older men. Design A cross-sectional study with a standardized validated diet history assessment and comprehensive oral hea...
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The recent use of the tail-tip bleeding approach in mice has enabled researchers to generate detailed pulse and surge profiles of luteinizing hormone (LH) secretion in mice. However, the analysis of pulsatile LH secretion is piecemeal across the field with each laboratory using their own methodology. We have reformulated the once popular PULSAR alg...
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Background Associations of chronic and intrusive pain with sarcopenia and disability in older men are unclear. Methods 1452 community-dwelling men aged ≥70 years self-reported chronic pain (pain every day for ≥3 months) and intrusive pain (pain interfering with normal activities in the last 4 weeks) at baseline and five years later, and were class...
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Objectives Mediterranean dietary patterns may exert favorable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men. Methods Seven hundred ninety-four (794) community-dwelling men...
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Objective: To define the optimized inter-injection interval of injectable testosterone undecanoate (TU) treatment for hypogonadal and transmen based on individual dose titration in routine clinical practice. Design and Methods: Prolective observational study of consecutive TU injections in men undergoing testosterone replacement therapy for patholo...
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Objectives Clinical evaluation of vitamin D status is conventionally performed by measuring serum levels of a single vitamin D metabolite, 25-hydroxyvitamin D predominantly by immunoassay methodology. However, this neglects the complex metabolic pathways involved in vitamin D bioactivity, including two canonical forms D3 and D2, bioactive 1,25-dihy...
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Background: Data in the Offspring Framingham Osteoporosis Study (FOS) suggested that higher intake of dietary fiber was modestly protective against loss of bone mineral density at the femoral neck in men but not in women. Aim: To examine the relationship of fiber intake with risk of hip fractures in men. Methods: We included 367 men from the F...
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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...
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Wound healing is a complex process involving four overlapping phases: haemostasis, inflammation, cell recruitment and matrix remodeling. In mouse models, surgical, pharmacological and genetic approaches targeting androgen actions in skin have shown that androgens increase interleukin-6 and tumor necrosis factor-α production and reduce wound re-epit...
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Background Unintended weight loss and the reduction in appetite are common phenomenon among older people. Reduced appetite has been linked to medication related reductions in saliva production, reduced taste ability and poor oral health. Poor appetite can result in reduced nutrient intake ensuing weight loss. It is possible that poor appetite is a...
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Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, however the etiology and pathogenesis of PCOS are poorly understood and current management is symptom based. Defining the pathogenesis of PCOS traits is important for developing early PCOS detection markers and new treatment strategies. Hyperandrogenism is a defining characteristi...
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Background Non-invasive self-testing using an objective chemical method to detect ovulation is valuable for women planning conception, practising contraception or undergoing infertility investigations or treatment. Methods Based on luteal phase secretion of progesterone (P4) and excretion of its major metabolite, pregnanediol glucuronide (PDG), we...
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We reviewed the available animal and human reproductive function studies of recently‐approved non‐cytotoxic oncology drugs. We reviewed the oncofertility information in the prescribing information for Food and Drug Administration (FDA)‐approved products and/or the product information and consumer medicine information for Therapeutic Goods Administr...
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Although characteristic changes in amino acid concentrations occur in obesity and sarcopenia, amino acids concentrations have not been reported in sarcopenic obesity. We studied n=831 men aged 75 years and older from the five-year follow-up of the Concord Health and Ageing in Men Project (CHAMP). Sarcopenia was defined using the Foundation of the N...
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Context Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. Objective Determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT). Design, Setting, Par...
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Background: Type 2 diabetes mellitus (T2DM) increases falls and fracture risk. Our objective was to compare incidence and risk factors for falls and fractures in community-dwelling older men with and without T2DM. Methods: A total of 1,705 men (471 with T2DM; 1234 without T2DM) aged ≥70 years were assessed at baseline. Men were contacted every 4...
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Background: Socioeconomic status (SES) has been suggested as a risk factor for falls but the few prospective studies to test this have had mixed results. We evaluated the prospective association between SES and falls in the Concord Health and Ageing in Men Project (CHAMP). Method: CHAMP is a population-based prospective cohort study of men aged...
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Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition characterised by a range of endocrine, reproductive and metabolic abnormalities. At present, management of women with PCOS is suboptimal as treatment is only symptomatic. Clinical and experimental advances in our understanding of PCOS etiology support a pivotal role for androgen ne...
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PurposeThe objectives of the study were to evaluate the associations between antioxidant intake, dietary patterns and depressive symptoms among older men.Method794 men participated in a detailed diet history interview at the Concord Health and Ageing in Men Project 3rd wave (considered baseline nutrition) and 781 men participated at the 4th wave (c...
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Objective To investigate the association between home ownership and health in older men. Methods Cross‐sectional analysis of 909 community‐dwelling Australian men (mean age: 81.3 ± 4.6) from the Concord Health and Ageing in Men Project (CHAMP, 2012‐2013). We considered self‐rated health, frailty status, multimorbidity, and anxiety and depressive s...
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Androgens are potent drugs requiring prescription for valid medical indications but are misused for invalid, unproven, or off-label reasons as well as being abused without prescription for illicit non-medical application for performance or image enhancement. Following discovery and first clinical application of testosterone in the 1930s, commercial...
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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...
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Objective Sex steroid levels in women vary with increasing age from the age of 70 years (70+). Whether this reflects change within individuals with age or a survival advantage is not known. This study aimed to determine the stability of circulating sex steroids and SHBG over time in individual women aged 70+. Design A prospective cohort study. Pa...
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Background and aims The role of antioxidant intake in cardiovascular disease remains inconclusive. This study evaluates the association between antioxidant intake and the risk of major adverse cardiovascular events (MACE) among older Australian men. Methods and results 794 men aged ≥75 years participated in the 3rd wave of the Concord Health and A...
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High‐impact physical activities with bone strains of high magnitude and frequency may benefit bone health. This study aimed to investigate the longitudinal associations between changes in loading intensities and application rates, estimated from self‐reported physical activity, with bone mineral density (BMD) changes over five years, and also with...
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Lifestyle, mainly dietary, interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. We combined a hyperandrogenized PCOS mouse model with a systematic macronutrient approach, to elucidate the impact of dietary macronutrients on the development of PCOS. We identify that an optimu...
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While high levels of glucocorticoids are generally neuro-damaging, a related adrenal steroid, dehydroepiandrosterone (DHEA), has anti-glucocorticoid and neuroprotective properties. Previous work has shown increased circulating levels of DHEA and abnormal cortisol/DHEA ratios in people with schizophrenia, however reports are limited and their relati...
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Objective: To assess the associations between nutrient intake and dietary patterns with different sarcopenia definitions in older men. Design: Cross-sectional study. Setting: Sarcopenia was defined using the Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP) and the Europe...
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Background Among older people, the extent to which psychosocial factors explain socioeconomic inequalities in mortality is debated. We aimed to investigate the potential mediating effect of psychosocial factors on socioeconomic inequalities in mortality. Methods We used data from a prospective population-based cohort (the Concord Health and Ageing...
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Background: Assessing perceived needs for dental treatment is important in understanding and predicting people's health behaviours. The purpose of this study is to examine older men's perceptions regarding dental treatment needs, and to investigate the disparity between perceived needs and the actual oral health of a population of community-dwelli...
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Androgens have been known to inhibit cutaneous wound healing in men and male mice. However, in children with major burn injuries, a synthetic androgen was reported clinically to improve wound healing. The aim of this study is to investigate the role of dihydrotestosterone (DHT) as a new therapeutic approach in treating major burn injury. In the pre...
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Objectives To estimate the impact on testosterone prescribing over 3 years following the 2015 tightening of Pharmaceutical Benefits Scheme (PBS) criteria. Design Analysis of testosterone prescribing data from PBS and private (non‐PBS) sources between 2012 and 2018 covering 2015 change in PBS prescribing criteria. Main outcome measures New and tot...
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Background: Conflicting evidence exists regarding the association of socioeconomic status (SES) with mortality among older people and little is known about the mechanisms underlying this association. We investigated the association of SES with mortality among older Australian men. We also investigated potential mediating effects of health-related...
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Estimating breeding performance from mouse mating trials has focused on lifetime mating trials which are too slow and costly for characterizing the many novel genetic mouse lines produced in fertility research, an underpinning of reproductive pathophysiology research. This study introduces the fertility index, defined as the slope of the regression...
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Accurate measurement of very low circulating estradiol (E2) (<5 pg/ml) in post-menopausal women and in mice is essential to investigating sex steroid action in target tissues. However, direct immunoassays are too inaccurate and conventional mass spectrometry-based measurement too insensitive at these serum E2 levels. We report application of an ult...
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Importance After menopause estradiol (E2) is predominately an intracrine hormone circulating in very low serum concentrations. Objective To examine determinants of E2 concentrations in women beyond 70 years. Design and setting A cross-sectional, community based, study. Participants 5325 women, mean age 75.1 (± 4.2) years, not using any sex stero...
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Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanis...