Medicine (Austin & Northern Health) - Research Publications
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ItemThe effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment(WILEY, 2017-10)BACKGROUND: Testosterone treatment in obese dieting men augments the diet-associated loss of fat mass, but protects against loss of lean mass. We assessed whether body composition changes are maintained following withdrawal of testosterone treatment. METHODS: We conducted a prespecified double-blind randomized placebo-controlled observational follow-up study of a randomized controlled trial (RCT). Participants were men with baseline obesity (body mass index >30 kg/m2 ) and a repeated total testosterone level <12 nmol/L, previously enrolled in a 56-week testosterone treatment trial combined with a weight loss programme. Main outcome measures were mean adjusted differences (MAD) (95% confidence interval), in body composition between testosterone- and placebo-treated men at the end of the observation period. RESULTS: Of the 100 randomized men, 82 completed the RCT and 64 the subsequent observational study. Median [IQR] observation time after completion of the RCT was 82 weeks [74; 90] in men previously receiving testosterone (cases) and 81 weeks [67;91] in men previously receiving placebo (controls), P=.51. At the end of the RCT, while losing similar amounts of weight, cases had, compared to controls, lost more fat mass, MAD -2.9 kg (-5.7, -0.2), P=.04, but had lost less lean mass MAD 3.4 kg (1.3, 5.5), P=.002. At the end of the observation period, the former between-group differences in fat mass, MAD -0.8 kg (-3.6, 2.0), P=1.0, in lean mass, MAD -1.3 kg (-3.0, 0.5), P=.39, and in appendicular lean mass, MAD -0.1 kg/m2 (-0.3, 0.1), P=.45, were no longer apparent. During observation, cases lost more lean mass, MAD -3.7 kg (-5.5, -1.9), P=.0005, and appendicular lean mass, MAD -0.5 kg/m2 (-0.8, -0.3), P<.0001 compared to controls. CONCLUSIONS: The favourable effects of testosterone on body composition in men subjected to a concomitant weight loss programme were not maintained at 82 weeks after testosterone treatment cessation.
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ItemQuality of life decrements in men with prostate cancer undergoing androgen deprivation therapy(WILEY, 2017-03)OBJECTIVE: While androgen deprivation therapy (ADT) has been associated with decreased quality of life (QoL), controlled prospective studies are lacking. We aimed to assess QoL during ADT using two validated questionnaires and determine contributing factors. DESIGN: Prospective controlled study. PATIENTS: Sixty-three men with nonmetastatic prostate cancer newly commencing ADT (n = 34) and age- and radiotherapy-matched prostate cancer controls (n = 29). MEASUREMENTS: QoL was measured by Short-Form 12 version 2 survey (SF-12) and Aging Males' Symptoms (AMS) score at 0, 6 and 12 months. Generalized linear models determined the mean adjusted difference (MAD) (95% confidence interval) between groups during follow-up. RESULTS: Compared to controls over 12 months, men receiving ADT had decreased SF-12 physical component score [MAD -3·61 (-6·94, -0·29), P = 0·013] reflecting worsening QoL but no change in the mental component (P = 0·74). Total AMS score increased [MAD 9·35 (5·65, 13·07), P < 0·001], reflecting worse QoL. Both SF-12 and AMS changes were greater than reported minimum clinically important differences. AMS sub-domains showed increased somatic [MAD 3·96 (1·94, 5·99), P < 0·001] and sexual [MAD 3·80 (2·16, 5·44), P < 0·001] components but not psychological (P = 0·19). Decrements were related to an increase in hot flushes (P = 0·016) but not haemoglobin decrease (P = 0·46). CONCLUSIONS: Within 12 months, ADT is associated with clinically significant decreased QoL, particularly physical and sexual aspects, independent of the confounding effects of a cancer diagnosis or radiotherapy. As QoL is a crucial aspect of prostate cancer treatment, addressing hot flushes, sexual dysfunction and exercise may potentially improve outcomes for men undergoing ADT.
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ItemPosition statement on the hormonal management of adult transgender and gender diverse individuals(Australasian Medical Publishing Company, 2019-08-01)Introduction: Rising demand for gender-affirming hormone therapy mandates a need for more formalised care of transgender and gender diverse (TGD) individuals in Australia. Estimates suggest that 0.1–2.0% of the population are TGD, yet medical education in transgender health is lacking. We aim to provide general practitioners, physicians and other medical professionals with specific Australian recommendations for the hormonal and related management of adult TGD individuals. Main recommendations: Hormonal therapy is effective at aligning physical characteristics with gender identity and in addition to respectful care, may improve mental health symptoms. Masculinising hormone therapy options include transdermal or intramuscular testosterone at standard doses. Feminising hormone therapy options include transdermal or oral estradiol. Additional anti-androgen therapy with cyproterone acetate or spironolactone is typically required. Treatment should be adjusted to clinical response. For biochemical monitoring, target estradiol and testosterone levels in the reference range of the affirmed gender. Monitoring is suggested for adverse effects of hormone therapy. Preferred names in use and pronouns should be used during consultations and reflected in medical records. While being TGD is not a mental health disorder, individualised mental health support to monitor mood during medical transition is recommended. Changes in management as result of this position statement Gender-affirming hormone therapy is effective and, in the short term, relatively safe with appropriate monitoring. Further research is needed to guide clinical care and understand long term effects of hormonal therapies. We provide the first guidelines for medical practitioners to aid the provision of gender-affirming care for Australian adult TGD individuals.
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ItemMetformin: time to review its role and safety in chronic kidney disease(WILEY, 2019-07)■Metformin is recommended as first-line therapy for type 2 diabetes because of its safety, low cost and potential cardiovascular benefits. ■The use of metformin was previously restricted in people with chronic kidney disease (CKD) - a condition that commonly coexists with diabetes - due to concerns over drug accumulation and metformin-associated lactic acidosis. ■There are limited data from observational studies and small randomised controlled trials to suggest that metformin, independent of its antihyperglycaemic effects, may be associated with lower risk of myocardial infarction, stroke and all-cause mortality in people with type 2 diabetes and CKD. ■Research into the risk of metformin-associated lactic acidosis in CKD has previously been limited and conflicting, resulting in significant variation across international guidelines on the safe prescribing and dosing of metformin at different stages of renal impairment. ■Present-day large scale cohort studies now provide supporting evidence for the safe use of metformin in mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73m2 ). However, prescribing metformin in people with severe renal impairment (eGFR < 30 mL/min/1.73m2 ) remains a controversial issue. Due to observed increased risk of lactic acidosis and all-cause mortality in people with type 2 diabetes and severe renal impairment, it is generally recommended that metformin is discontinued if renal function falls below this level or during acute renal deterioration.
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ItemCross-sex hormone therapy in Australia: the prescription patterns of clinicians experienced in adult transgender healthcare(WILEY, 2019-02)BACKGROUND: Despite increasing demand for transgender healthcare, guidelines for cross-sex hormone therapy are based on low-level evidence only. As most data are based on international expert opinions, interpretations and practices vary significantly. AIMS: To aid the development of Australian clinical guidelines, we aimed to identify cross-sex hormone therapy prescribing patterns among medical practitioners experienced in adult transgender healthcare. METHODS: We conducted an anonymous online survey of experienced hormone prescribers who were members of the Australian and New Zealand Professional Association for Transgender Health (ANZPATH). RESULTS: We received 35 responses from 43 individuals listed with ANZPATH. Mental health assessments prior to commencement of hormonal therapy were recommended by 80% of prescribers. The preferred first-line masculinising hormone therapy was intramuscular testosterone undecanoate (46% of respondents). The most commonly prescribed feminising agents were oral estradiol valerate (first line in 71.4%), with either spironolactone or cyproterone acetate. Most respondents (>90%) targeted sex steroid reference ranges of the affirmed gender, and 71.4% reviewed individuals every 2-3 months in the first year. Better training for doctors was seen as the most pressing priority for government funding, and 79.3% supported the development of local Australian-based guidelines. CONCLUSIONS: Experienced hormone prescribers in Australia largely use medication regimens and monitor sex steroid levels and potential adverse effects of sex hormone therapy in accordance with broad, subjective recommendations listed in international guidelines. Additional practitioner training is necessary, and local Australian-based guidelines would offer specific, relevant guidance to clinicians in the initiation and monitoring of cross-sex hormone therapy for adult transgender individuals.
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ItemGender-affirming hormone therapy and the risk of sex hormone-dependent tumours in transgender individuals-A systematic review(WILEY, 2018-12)BACKGROUND: Cancers are a leading cause of death worldwide, and transgender individuals are no exception. The effects of gender-affirming hormone therapy (GAHT) on sex hormone-dependent tumours are unclear. Therefore, this review seeks to determine whether tumour risk in transgender individuals differs from the general population, to guide clinical screening recommendations. METHODS: We performed a systematic review based on the PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining tumour incidence, prevalence or cancer-related mortality in transgender individuals. All English peer-reviewed publications were included if histological type and temporal relation to GAHT were reported. Case reports were included if there were ≥2 cases of the same histological type. RESULTS: The search strategy identified 307 studies. Excluding those that did not meet inclusion criteria, 43 studies (7 cohort studies, 2 cross-sectional studies and 34 case reports) were reviewed. Retrospective cohort studies suggest no increase in risk of tumour development in transgender individuals receiving GAHT compared to the general population. Notably, the mean ages of cohorts were young and were treated with GAHT for insufficient durations to assess tumour risk. Case reports raise potential associations between high-dose oestradiol and anti-androgen therapy with prolactinoma and meningioma, respectively. CONCLUSIONS: Further longitudinal studies are required to assess the risk of GAHT and hormone-dependent tumour development. Until further evidence is available, tumour screening should be based on guidelines for the general population and the presence of organs in transgender individuals rather than gender identity or hormonal therapy status.
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ItemUsing Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes (vol 12, e0168471, 2017)(PUBLIC LIBRARY SCIENCE, 2017-02-13)[This corrects the article DOI: 10.1371/journal.pone.0168471.].