Publications by authors named "Jeffrey Zajac"

143 Publications

Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial.

J Clin Neurosci 2021 Apr 2;86:103-109. Epub 2021 Feb 2.

Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia. Electronic address:

Aims: Pre-diabetes is a common condition that affects about 16.4% of Australian adults. Hyperglycaemia is a strong risk factor for the development of stroke. Metformin XR is an approved medication to treat type 2 diabetes in Australia but not pre-diabetes. Additionally, whether it is tolerated following a stroke is unclear. In this pilot study, we aimed to assess the feasibility of Metformin XR in people with stroke and pre-diabetes.

Methods: In this PROBE design trial, people who had recent stroke (within 3 months) with pre-diabetes were randomized to either the active arm (n = 13) receiving usual care plus Metformin XR (500 mg daily increased to a total daily dose of 1500 mg) or the control group receiving only usual care (n = 13). At baseline & after four months of intervention, clinical and biomedical characteristics, cardiovascular risk factors and medication data were recorded. At one month and 2.5 months into the study, compliance rateandside effects were determined.

Results: This trial showed that it is feasible to recruit, retain and monitor participants. However, the compliance rate was low. Adherence to metformin XR was 52% (IQR:42% to 61%) based on the remaining tablets in the container after 4 months of intervention. None of the reported side effects were deemed to be related to the study treatment and no significant differences were observed between the metformin XR and the control group.

Conclusion: Treatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe. Strategies are needed to improve adherence in future trials.
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http://dx.doi.org/10.1016/j.jocn.2021.01.006DOI Listing
April 2021

Effect of Testosterone treatment on bone microarchitecture and bone mineral density in men: a two-year RCT.

J Clin Endocrinol Metab 2021 Mar 8. Epub 2021 Mar 8.

Department of Medicine (Austin Health), The University of Melbourne, Victoria, Australia.

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, Participants: Men>50 years were recruited from six Australian centres.

Interventions: Injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program.

Main Outcomes: Primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (one centre). Secondary endpoints included other HR-pQCT parameters and bone remodelling markers. Areal BMD (aBMD) was measured by dual energy X-ray absorptiometry (DXA) in 601 men (five centres). Using a linear mixed model for repeated measures, the mean adjusted differences (MAD) [95% CI] at 12 and 24 months between groups are reported as treatment effect.

Results: Over 24 months, testosterone treatment, compared to placebo, increased tibial cortical vBMD), 9.33mgHA/cm 3[3.96;14.71],p<0.001 or 3.1%[1.2;5.0], radial cortical vBMD, 8.96mgHA/cm 3[3.30;14.62],p=0.005 or 2.9%[1.0;4.9], total tibial vBMD, 4.16mgHA/cm 3[2.14;6.19],p<0.001 or 1.3%[0.6;1.9] and total radial vBMD, 4.42mgHA/cm 3[1.67;7.16],p=0.002 or 1.8%[0.4;2.0]. Testosterone also significantly increased cortical area and thickness at both sites. Effects on trabecular architecture were minor. Testosterone reduced bone remodeling markers CTX, -48.1ng/L[-81.1;-15.1],p<0.001, and P1NP, -6.8μg/L[-10.9;-2.7], p<0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm 2[0.03;0.05],p<0.001, and the total hip, 0.01g/cm 2[0.01;0.02],p<0.001.

Conclusions: In men>50 years, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.
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http://dx.doi.org/10.1210/clinem/dgab149DOI Listing
March 2021

The calcitonin receptor regulates osteocyte lacunae acidity during lactation in mice.

J Endocrinol 2021 Apr;249(1):31-41

Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.

The physiological role of calcitonin, and its receptor, the CTR (or Calcr), has long been debated. We previously provided the first evidence for a physiological role of the CTR to limit maternal bone loss during lactation in mice by a direct action on osteocytes to inhibit osteocytic osteolysis. We now extend these findings to show that CTR gene expression is upregulated two- to three-fold in whole bone of control mice at the end of pregnancy (E18) and lactation (P21) compared to virgin controls. This was associated with an increase in osteoclast activity evidenced by increases in osteoclast surface/bone surface and Dcstamp gene expression. To investigate the mechanism by which the CTR inhibits osteocytic osteolysis, in vivo acidification of the osteocyte lacunae during lactation (P14 days) was assessed using a pH indicator dye. A lower pH was observed in the osteocyte lacunae of lactating Global-CTRKOs compared to controls and was associated with an increase in the gene expression of ATPase H+ transporting V0 subunit D2 (Atp6v0d2) in whole bone of Global-CTRKOs at the end of lacation (P21). To determine whether the CTR is required for the replacement of mineral within the lacunae post-lactation, lacunar area was determined 3 weeks post-weaning. Comparison of the largest 20% of lacunae by area did not differ between Global-CTRKOs and controls post-lactation. These results provide evidence for CTR activation to inhibit osteocytic osteolysis during lactation being mediated by regulating the acidity of the lacunae microenvironment, whilst the CTR is dispensable for replacement of bone mineral within lacunae by osteocytes post-lactation.
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http://dx.doi.org/10.1530/JOE-20-0599DOI Listing
April 2021

The calcitonin receptor regulates osteocyte lacunae acidity during lactation in mice.

J Endocrinol 2021 Apr;249(1):31-41

Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.

The physiological role of calcitonin, and its receptor, the CTR (or Calcr), has long been debated. We previously provided the first evidence for a physiological role of the CTR to limit maternal bone loss during lactation in mice by a direct action on osteocytes to inhibit osteocytic osteolysis. We now extend these findings to show that CTR gene expression is upregulated two- to three-fold in whole bone of control mice at the end of pregnancy (E18) and lactation (P21) compared to virgin controls. This was associated with an increase in osteoclast activity evidenced by increases in osteoclast surface/bone surface and Dcstamp gene expression. To investigate the mechanism by which the CTR inhibits osteocytic osteolysis, in vivo acidification of the osteocyte lacunae during lactation (P14 days) was assessed using a pH indicator dye. A lower pH was observed in the osteocyte lacunae of lactating Global-CTRKOs compared to controls and was associated with an increase in the gene expression of ATPase H+ transporting V0 subunit D2 (Atp6v0d2) in whole bone of Global-CTRKOs at the end of lacation (P21). To determine whether the CTR is required for the replacement of mineral within the lacunae post-lactation, lacunar area was determined 3 weeks post-weaning. Comparison of the largest 20% of lacunae by area did not differ between Global-CTRKOs and controls post-lactation. These results provide evidence for CTR activation to inhibit osteocytic osteolysis during lactation being mediated by regulating the acidity of the lacunae microenvironment, whilst the CTR is dispensable for replacement of bone mineral within lacunae by osteocytes post-lactation.
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http://dx.doi.org/10.1530/JOE-20-0599DOI Listing
April 2021

Insulin resistance in transgender individuals correlates with android fat mass.

Ther Adv Endocrinol Metab 2021 23;12:2042018820985681. Epub 2021 Jan 23.

Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084, Australia.

Background: Transgender individuals receiving gender-affirming hormone therapy (GAHT) are at increased risk of adverse cardiovascular outcomes. This may be related to effects on body composition and insulin resistance.

Aims: To examine relationships between body fat distribution and insulin resistance in transgender individuals on established GAHT.

Methods: Comparisons of body composition (dual energy X-ray absorptiometry) and insulin resistance [Homeostasis Model of Insulin Resistance (HOMA2-IR)] were made between transgender individuals (43 trans men and 41 trans women) on established GAHT (>12 months) and age-matched cisgender controls (30 males and 48 females). Multiple linear regressions were used to examine the relationship between HOMA2-IR and fat mass with gender, adjusting for age and total duration of GAHT and Pearson correlation coefficients are reported.

Results: Compared with control cisgender women, trans men had mean difference of +7.8 kg (4.0, 11.5),  < 0.001 in lean mass and higher android:gynoid fat ratio [0.2 (0.1, 0.3),  < 0.001], but no difference in overall fat mass or insulin resistance. Compared with control cisgender men, trans women had median difference in lean mass of -6.9 kg (-10.6, -3.1),  < 0.001, fat mass of +9.8 kg (3.9, 14.5),  = 0.001, lower android:gynoid fat ratio -0.1 (-0.2,-0.0),  < 0.05), and higher insulin resistance 1.6 (1.3-1.9),  < 0.001). Higher HOMA2-IR correlated with higher android ( = 0.712,  < 0.001) and gynoid ( = 0.572,  < 0.001) fat mass in both trans men and trans women.

Conclusion: Android fat more strongly correlates with insulin resistance than gynoid fat in transgender individuals. Higher fat mass and insulin resistance in trans women may predispose to increased cardiovascular risk. Despite adverse fat distribution, insulin resistance was not higher in trans men.
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http://dx.doi.org/10.1177/2042018820985681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841663PMC
January 2021

The Health and Well-Being of Transgender Australians: A National Community Survey.

LGBT Health 2021 01 9;8(1):42-49. Epub 2020 Dec 9.

Department of Medicine (Austin Health), The University of Melbourne, Victoria, Australia.

Transgender, including gender diverse and nonbinary (trans), people experience significant health disparities. We aimed to better understand the health status and needs of Australian trans people to guide resources and health and well-being programs. This anonymous, cross-sectional online survey utilized nonprobability snowball sampling of Australian adults (18 years and over) who self-identified as trans between September 2017 and January 2018. This descriptive study assessed demographic data, community views on access to health care, health burden, access to health resources, and priorities for government funding in transgender health. Of 928 participants, 37% reported female, 36% reported male, and 27% reported nonbinary gender identities. Despite 47% having tertiary qualifications, the unemployment rate was 19%, with 33% reporting discrimination in employment due to being trans. Discrimination in accessing health care was reported by 26% and verbal abuse and physical assault were reported by 63% and 22%, respectively. Lifetime diagnosis of depression was reported by 73% and anxiety by 67%. Sixty-three percent reported previous self-harm and 43% had attempted suicide. Autism spectrum disorder and attention-deficit/hyperactivity disorder were reported by 15% and 11%, respectively. The most preferred method of receiving health information was through online resources, with the most popular source being Reddit, an online peer discussion board. Better training for doctors in trans health issues was the top priority for government funding. Barriers, including widespread discrimination and unemployment, contribute to health inequity and prevalent mental health conditions. Better training for health professionals in the provision of safe, gender-affirming and general health care for trans people is urgently required.
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http://dx.doi.org/10.1089/lgbt.2020.0178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826417PMC
January 2021

The Informed Consent Model of Care for Accessing Gender-Affirming Hormone Therapy Is Associated With High Patient Satisfaction.

J Sex Med 2021 01 26;18(1):201-208. Epub 2020 Nov 26.

Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia. Electronic address:

Background: There are 2 common approaches to assess an individual before commencing of gender-affirming hormone therapy (GAHT); a mental health practitioner assessment and approval or an informed consent model undertaken with a primary care general practitioner (GP).

Aim: In a primary care clinic practising an Informed Consent Model of care to initiate GAHT, we aimed to firstly describe the proportion and characteristics of patients referred for secondary consultation to a mental health practitioner (MH referred) and secondly, we aimed to measure patient satisfaction.

Methods: A retrospective audit of all new patients with a transgender or gender diverse identity presenting to a primary care clinic in Melbourne, Australia was performed between March 2017 and March 2019. In those newly seeking GAHT, de-identified data were obtained including presence of secondary mental health practitioner referral, time to GAHT commencement and co-occurring mental health conditions. A separate survey assessed patient satisfaction.

Outcomes: Mental health conditions and overall patient satisfaction in those referred for secondary mental health consultation (MH referred) were compared with those who were not (GP assessed).

Results: Of 590 new consultations, 309 were newly seeking GAHT. Referrals for secondary mental health assessment before GAHT occurred in 8%. The GP-assessed group commenced GAHT at median 0.9 months (0.5-1.8) after initial consultation compared with 3.1 months (1.3-4.0), P < .001 in the MH-referred group. The MH-referred group was more likely to have post-traumatic stress disorder (adjusted P = .036) and schizophrenia (adjusted P = .011). Of 43 respondents to the survey, a higher proportion in the GP-assessed group was extremely satisfied with their overall care compared with the MH-referred group (P < .01). Notably, 80% in the GP-assessed group chose to seek mental health professional support.

Clinical Implications: Initiation of GAHT can be performed in primary care by GPs using an informed consent model and is associated with high patient satisfaction. Mental health professionals remain a key source of support.

Strengths & Limitations: This retrospective audit did not randomize patients to pathways to initiate GAHT. Follow-up duration was short. Responder bias to survey with low response rates may overestimate patient satisfaction. This is one of the first studies to evaluate an informed consent model of care.

Conclusion: More widespread uptake of an informed consent model of care to initiate GAHT by primary care physicians has the potential for high patient satisfaction and may be a practical solution to reduce waiting lists in gender clinics. Spanos C, Grace JA, Leemaqz SY, et al. The Informed Consent Model of Care for Accessing Gender-Affirming Hormone Therapy Is Associated With High Patient Satisfaction. J Sex Med 2021;18:201-208.
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http://dx.doi.org/10.1016/j.jsxm.2020.10.020DOI Listing
January 2021

Paracrine signalling by cardiac calcitonin controls atrial fibrogenesis and arrhythmia.

Nature 2020 11 4;587(7834):460-465. Epub 2020 Nov 4.

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fibrosis and increases susceptibility to atrial fibrillation. In mice in which liver kinase B1 is knocked down specifically in the atria, atrial-specific knockdown of calcitonin promotes atrial fibrosis and increases and prolongs spontaneous episodes of atrial fibrillation, whereas atrial-specific overexpression of calcitonin prevents both atrial fibrosis and fibrillation. Human patients with persistent atrial fibrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fibroblast membrane. Although transcriptome analysis of human atrial fibroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fibrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may offer therapeutic avenues for patients with atrial fibrillation.
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http://dx.doi.org/10.1038/s41586-020-2890-8DOI Listing
November 2020

A systematic review of antiandrogens and feminization in transgender women.

Clin Endocrinol (Oxf) 2020 Sep 14. Epub 2020 Sep 14.

Department of Medicine, The University of Melbourne, Heidelberg, Vic., Australia.

Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects of testosterone, but it is unclear which antiandrogen is most effective at feminization. A systematic review was performed using PRISMA guidelines. We searched online databases (Medline, Embase and PsycINFO) and references of relevant articles for studies of antiandrogens in transgender women aged 16+ years to achieve feminization (namely changes in breast size, body composition, facial or body hair) or changes in serum total testosterone concentration when compared to placebo, estradiol alone or an alternative antiandrogen. Four studies fulfilled eligibility criteria and were included in a narrative review. The addition of cyproterone acetate, leuprolide and medroxyprogesterone acetate may be more effective than spironolactone or estradiol alone at suppressing the serum total testosterone concentration. Body composition changes appear similar in transgender women treated with estradiol and additional cyproterone acetate or leuprolide. No eligible studies adequately evaluated the effects of antiandrogens on breast development or facial and body hair reduction. It remains unclear which antiandrogen is most effective at achieving feminization. Cyproterone acetate, medroxyprogesterone acetate and leuprolide may be more effective than spironolactone at suppressing the serum total testosterone concentration. However, due to spironolactone's antagonism of the androgen receptor, it is unclear whether this results in clinically meaningful differences in feminization. Further research with clinically meaningful endpoints is needed to optimize the use of antiandrogens in transgender women.
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http://dx.doi.org/10.1111/cen.14329DOI Listing
September 2020

Approach to Interpreting Common Laboratory Pathology Tests in Transgender Individuals.

J Clin Endocrinol Metab 2021 Mar;106(3):893-901

Trans Health Research group, Department of Medicine (Austin Health), The University of Melbourne, Victoria, Australia.

Context: As the number of transgender (trans) people (including those who are binary and/or nonbinary identified) seeking gender-affirming hormone therapy rises, endocrinologists are increasingly asked to assist with interpretation of laboratory tests. Many common laboratory tests such as hemoglobin, iron studies, cardiac troponin, and creatinine are affected by sex steroids or body size. We seek to provide a summary of the impact of feminizing and masculinizing hormone therapy on common laboratory tests and an approach to interpretation.

Cases: Case scenarios discussed include 1) hemoglobin and hematocrit in a nonbinary person undergoing masculinizing hormone therapy; 2) estimation of glomerular filtration rate in a trans woman at risk of contrast-induced nephropathy; 3) prostate-specific antigen (PSA) in a trans woman; and 4) chest pain in a trans man with a cardiac troponin concentration between the reported male and female reference ranges.

Conclusions: The influence of exogenous gender-affirming hormone therapy on fat and muscle distribution and other physiological changes determines interpretation of laboratory tests that have sex-specific differences. In addition to affirmative practice to ensure a patient's name, gender, and pronoun are used appropriately, we propose that once individuals have commenced gender-affirming hormone therapy, the reference range of the affirmed gender be reported (and specified by treating clinicians) except for PSA or cardiac troponin, which are dependent on organ size. While suggestions may be challenging to implement, they also represent an opportunity to lead best practice to improve the quality of care and experiences of healthcare for all trans people.
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http://dx.doi.org/10.1210/clinem/dgaa546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947878PMC
March 2021

Relationships between body mass index with oral estradiol dose and serum estradiol concentration in transgender adults undergoing feminising hormone therapy.

Ther Adv Endocrinol Metab 2020 24;11:2042018820924543. Epub 2020 May 24.

Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.

Aim: Feminising hormone therapy with estradiol is used to align an individual's physical characteristics with their gender identity. Given considerable variations in doses of estradiol therapy administered as gender-affirming hormone therapy (GAHT), we aimed to assess if body mass index (BMI) correlated with estradiol dose/concentration and assess the correlation between estradiol dose and estradiol concentrations.

Methods: In a retrospective cross-sectional study, we analysed transgender individuals attending a primary or secondary care clinic in Melbourne, Australia who were prescribed oral estradiol valerate for at least 6 months and had estradiol dose and concentration available. Estradiol concentration was measured by immunoassay. Outcomes were the correlation between estradiol dose and BMI, and estradiol dose and estradiol concentration.

Results: Data were available for 259 individuals {median age 25.8 [interquartile range (IQR) 21.9, 33.5] years}. Median duration of estradiol therapy was 24 (15, 33) months. Median estradiol concentration was 328 (238, 434) pmol/l [89 (65, 118) pg/ml] on 6 (4, 8) mg estradiol valerate. Median BMI was 24.7 (21.8, 28.6) kg/m. There was a weak positive correlation between estradiol dose and estradiol concentration ( = 0.156,  = 0.012). There was no correlation between BMI and estradiol concentration achieved ( = -0.063,  = 0.413) or BMI and estradiol dose ( = 0.048,  = 0.536). Estradiol concentrations were within the target range recommended in consensus guidelines in 172 (66%) individuals.

Conclusion: Estradiol dose was only weakly correlated with estradiol concentration, suggesting significant interindividual variability. Prescription of estradiol dose should not be based upon an individual's BMI, which did not correlate with estradiol concentration achieved. In all, 66% of individuals achieved estradiol concentrations recommended in Australian consensus guidelines with a relatively high oral estradiol dose.
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http://dx.doi.org/10.1177/2042018820924543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249588PMC
May 2020

Differing Effects of Zoledronic Acid on Bone Microarchitecture and Bone Mineral Density in Men Receiving Androgen Deprivation Therapy: A Randomized Controlled Trial.

J Bone Miner Res 2020 10 6;35(10):1871-1880. Epub 2020 Jul 6.

Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Australia.

Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency, leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8 years (63.8 to 73.9) with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomized to zoledronic acid and 37 to matching placebo. Bone microarchitecture was measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). Using a mixed model, mean adjusted differences (MAD; 95% confidence interval [95% CI]) between the groups are reported as the treatment effect at several time points. Over 24 months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7 mg HA/cm [-2.0 to 15.4], p = 0.21) and tibia (1.9 mg HA/cm [-3.3 to 7.0], p = 0.87). Similarly, there were no between-group differences in other measures of microarchitecture, with the exception of a modest effect of zoledronic acid over placebo in total cortical vBMD at the radius over 12 months (17.3 mgHA/cm [5.1 to 29.5]). In contrast, zoledronic acid showed a treatment effect over 24 months on areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) at all sites, including lumbar spine (0.10 g/cm [0.07 to 0.13]), p < 0.001), and total hip (0.04 g/cm [0.03 to 0.05], p < 0.001). Bone remodeling markers were initially suppressed in the treatment group then increased but remained lower relative to placebo (MADs at 24 months CTX -176 ng/L [-275 to -76], p < 0.001; P1NP -18 mg/L [-32 to -5], p < 0.001). These findings suggest that a single dose of zoledronic acid over 2 years is ineffective in preventing the unbalanced bone remodeling and severe microstructural deterioration associated with ADT therapy. © 2020 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.4106DOI Listing
October 2020

Testosterone therapy considerations in oestrogen, progesterone and androgen receptor-positive breast cancer in a transgender man.

Clin Endocrinol (Oxf) 2020 09 26;93(3):355-357. Epub 2020 Jun 26.

Endocrinology Department, Austin Health, Heidelberg, Vic., Australia.

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http://dx.doi.org/10.1111/cen.14263DOI Listing
September 2020

Global Coagulation Assays in Transgender Women on Oral and Transdermal Estradiol Therapy.

J Clin Endocrinol Metab 2020 07;105(7)

Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia.

Context: The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests.

Objective: To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women.

Design: Cross-sectional case-control study.

Setting: General community.

Participants: Transgender women, cisgender male and cisgender female controls.

Main Outcome Measures: Citrated blood samples were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram); and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented.

Results: Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum amplitude + 6.94 mm (3.55, 10.33); P < 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91); P = 0.009; peak thrombin + 38.10 nM (2.27, 73.94); P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25); P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters.

Conclusion: Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters.
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http://dx.doi.org/10.1210/clinem/dgaa262DOI Listing
July 2020

Androgens stimulate erythropoiesis through the DNA-binding activity of the androgen receptor in non-hematopoietic cells.

Eur J Haematol 2020 Sep 15;105(3):247-254. Epub 2020 May 15.

Central Clinical School, Australian Centre for Blood Diseases, Monash University, Melbourne, Vic., Australia.

Background: Androgens function through DNA and non-DNA binding-dependent signalling of the androgen receptor (AR). How androgens promote erythropoiesis is not fully understood.

Design And Methods: To identify the androgen signalling pathway, we treated male mice lacking the second zinc finger of the DNA-binding domain of the AR (AR ) with non-aromatizable 5α-dihydrotestosterone (5α-DHT) or aromatizable testosterone. To distinguish direct hematopoietic and non-hematopoietic mechanisms, we performed bone marrow reconstitution experiments.

Results: In wild-type mice, 5α-DHT had greater erythroid activity than testosterone, which can be aromatized to estradiol. The erythroid response in wild-type mice following 5α-DHT treatment was associated with increased serum erythropoietin (EPO) and its downstream target erythroferrone, and hepcidin suppression. 5α-DHT had no erythroid activity in AR mice, proving the importance of DNA binding by the AR. Paradoxically, testosterone, but not 5α-DHT, suppressed EPO levels in AR mice, suggesting testosterone following aromatization may oppose the erythroid-stimulating effects of androgens. Female wild-type mice reconstituted with AR bone marrow cells remained responsive to 5α-DHT. In contrast, AR mice reconstituted with female wild-type bone marrow cells showed no response to 5α-DHT.

Conclusion: Erythroid promoting effects of androgens are mediated through DNA binding-dependent actions of the AR in non-hematopoietic cells, including stimulating EPO expression.
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http://dx.doi.org/10.1111/ejh.13431DOI Listing
September 2020

Non-Binary and Binary Gender Identity in Australian Trans and Gender Diverse Individuals.

Arch Sex Behav 2020 10 13;49(7):2673-2681. Epub 2020 Apr 13.

Murdoch Children's Research Institute and University of Melbourne (Department of Paediatrics), Royal Children's Hospital, Parkville, VIC, Australia.

Many trans and gender diverse (TGD) people have gender identities that are not exclusively male or female but instead fall in-between or outside of the gender binary (non-binary). It remains unclear if and how those with non-binary gender identity differ from TGD individuals with binary identities. We aimed to understand the sociodemographic and mental health characteristics of people with non-binary identities compared with binary TGD identities. We performed a retrospective audit of new consultations for gender dysphoria between 2011 and 2016 in three clinical settings in Melbourne, Australia; (1) Equinox Clinic, an adult primary care clinic, (2) an adult endocrine specialist clinic, and (3) the Royal Children's Hospital, a child and adolescent specialist referral clinic. Age (grouped by decade), gender identity, sociodemographic, and mental health conditions were recorded. Of 895 TGD individuals, 128 (14.3%) had a non-binary gender. Proportions differed by clinical setting; 30.4% of people attending the adult primary care clinic, 7.4% attending the adult endocrine specialist clinic, and 8.0% attending the pediatric clinic identified as non-binary. A total of 29% of people in the 21-30-year-old age-group had a non-binary gender identity, higher than all other age-groups. Compared to TGD people with a binary gender identity, non-binary people had lower rates of gender-affirming interventions, and a higher prevalence of depression, anxiety, and illicit drug use. Tailoring clinical services to be inclusive of non-binary people and strategies to support mental health are required. Further research to better understand health needs and guide evidence-based gender-affirming interventions for non-binary people are needed.
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http://dx.doi.org/10.1007/s10508-020-01689-9DOI Listing
October 2020

Prevalence of polycythaemia with different formulations of testosterone therapy in transmasculine individuals.

Intern Med J 2020 Apr 1. Epub 2020 Apr 1.

Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.

Background: Masculinising hormone therapy with testosterone is used to align an individual's physical characteristics with their gender identity. Testosterone therapy is typically administered via intramuscular or transdermal routes and polycythaemia is the most common adverse event.

Aims: To compare the risk of polycythaemia with different formulations of testosterone therapy in transmasculine individuals.

Methods: A retrospective cross-sectional analysis was undertaken of transmasculine individuals at a primary and secondary care clinic in Melbourne, Australia. 180 individuals who were on testosterone therapy for >6 months were included. Groups included those receiving (1) intramuscular testosterone undecanoate (n = 125), (2) intramuscular testosterone enantate (n = 31), or (3) transdermal testosterone (n = 24). Outcome was prevalence of polycythaemia (defined as haematocrit >0.5).

Results: Mean age was 28.4 (8.8) years with a median duration of testosterone therapy 37.7 (24.2) months. 27% were smokers. There was no difference between groups in serum total testosterone concentration measured. Whilst there was no difference between groups in haematocrit, there was a higher proportion of patients with polycythemia in those who were on intramuscular testosterone enantate (23.3%) than on transdermal testosterone (0%), p = 0.040. There was no statistically significant difference in polycythaemia between intramuscular testosterone undecanoate (15%) and transdermal, p = 0.066 nor between intramuscular testosterone enantate and undecanoate, p = 0.275.

Conclusions: One in four individuals treated with intramuscular testosterone enantate and one in six treated with testosterone undecanoate had polycythaemia. No individual treated with transdermal testosterone had polycythaemia. This highlights the importance of regular monitoring of haematocrit in transmasculine individuals treated with testosterone and findings may inform treatment choices. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.14839DOI Listing
April 2020

Effects of gender-affirming hormone therapy on insulin resistance and body composition in transgender individuals: A systematic review.

World J Diabetes 2020 Mar;11(3):66-77

Trans Medical Research Group, Department of Medicine (Austin Health), University of Melbourne, Victoria 3084, Australia.

Background: Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of adverse cardiovascular outcomes, including myocardial infarction and stroke. This may be related to the effects of testosterone or estradiol therapy on body composition, fat distribution, and insulin resistance but the effect of gender-affirming hormone therapy on these cardiovascular risk factors has not been extensively examined.

Aim: To evaluate the impact of gender-affirming hormone therapy on body composition and insulin resistance in transgender individuals, to guide clinicians in minimising cardiovascular risk.

Methods: We performed a review of the literature based on PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining body composition, insulin resistance or body fat distribution in transgender individuals aged over 18 years on established gender-affirming hormone therapy. Studies were selected for full-text analysis if they investigated transgender individuals on any type of gender-affirming hormone therapy and reported effects on lean mass, fat mass or insulin resistance.

Results: The search strategy identified 221 studies. After exclusion of studies that did not meet inclusion criteria, 26 were included (2 cross-sectional, 21 prospective-uncontrolled and 3 prospective-controlled). Evidence in transgender men suggests that testosterone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Evidence in transgender women suggests that feminising hormone therapy (estradiol, with or without anti-androgen agents) decreases lean mass, increases fat mass, and may worsen insulin resistance. Changes to body composition were consistent across almost all studies: Transgender men on testosterone gained lean mass and lost fat mass, and transgender women on oestrogen experienced the reverse. No study directly contradicted these trends, though several small studies of short duration reported no changes. Results for insulin resistance are less consistent and uncertain. There is a paucity of prospective controlled research, and existing prospective evidence is limited by small sample sizes, short follow up periods, and young cohorts of participants.

Conclusion: Further research is required to further characterise the impact of gender-affirming hormone therapy on body composition and insulin resistance in the medium-long term. Until further evidence is available, clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.
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http://dx.doi.org/10.4239/wjd.v11.i3.66DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061235PMC
March 2020

Sex-specific adipose tissue imprinting of regulatory T cells.

Nature 2020 03 26;579(7800):581-585. Epub 2020 Feb 26.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.

Adipose tissue is an energy store and a dynamic endocrine organ. In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism. Impaired VAT function-for example, in obesity-is associated with insulin resistance and type 2 diabetes. Regulatory T (T) cells that express the transcription factor FOXP3 are critical for limiting immune responses and suppressing tissue inflammation, including in the VAT. Here we uncover pronounced sexual dimorphism in T cells in the VAT. Male VAT was enriched for T cells compared with female VAT, and T cells from male VAT were markedly different from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. Heightened inflammation in the male VAT facilitated the recruitment of T cells via the CCL2-CCR2 axis. Androgen regulated the differentiation of a unique IL-33-producing stromal cell population specific to the male VAT, which paralleled the local expansion of T cells. Sex hormones also regulated VAT inflammation, which shaped the transcriptional landscape of VAT-resident T cells in a BLIMP1 transcription factor-dependent manner. Overall, we find that sex-specific differences in T cells from VAT are determined by the tissue niche in a sex-hormone-dependent manner to limit adipose tissue inflammation.
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http://dx.doi.org/10.1038/s41586-020-2040-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241647PMC
March 2020

Intestinal Pseudo-Obstruction and Livedo Reticularis: Rare Manifestations of Catecholamine Excess.

Am J Med 2020 09 27;133(9):e526-e527. Epub 2020 Jan 27.

Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, The University of Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1016/j.amjmed.2019.12.030DOI Listing
September 2020

Health Needs of Trans and Gender Diverse Adults in Australia: A Qualitative Analysis of a National Community Survey.

Int J Environ Res Public Health 2019 12 13;16(24). Epub 2019 Dec 13.

Trans Medical Research Group, Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria 3084, Australia.

There is an increasing demand for trans and gender diverse (TGD) health services worldwide. Given the unique and diverse healthcare needs of the TGD community, best practice TGD health services should be community-led. We aimed to understand the healthcare needs of a broad group of TGD Australians, how health professionals could better support TGD people, and gain an understanding of TGD-related research priorities. An anonymous online survey received 928 eligible responses from TGD Australian adults. This paper focuses on three questions out of that survey that allowed for free-text responses. The data were qualitatively coded, and overarching themes were identified for each question. Better training for healthcare professionals and more accessible transgender healthcare were the most commonly reported healthcare needs of participants. Findings highlight a pressing need for better training for healthcare professionals in transgender healthcare. In order to meet the demand for TGD health services, more gender services are needed, and in time, mainstreaming health services in primary care will likely improve accessibility. Evaluation of training strategies and further research into optimal models of TGD care are needed; however, until further data is available, views of the TGD community should guide research priorities and the TGD health service delivery.
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http://dx.doi.org/10.3390/ijerph16245088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950552PMC
December 2019

Australian endocrinologists need more training in transgender health: A national survey.

Clin Endocrinol (Oxf) 2020 03 1;92(3):247-257. Epub 2020 Jan 1.

Department of Endocrinology, Austin Health, Heidelberg, Vic., Australia.

Objective: An increasing number of trans and gender diverse (TGD) individuals are seeking gender-affirming hormone therapy for gender transition. Little is known about the levels of training, experience and confidence of endocrinologists in providing care and lack of training and experience is a potential barrier to individuals seeking appropriate and timely health care. We aimed to assess the level of training and confidence of Australian endocrinologists and trainees in the endocrine management of trans and gender diverse individuals in a representative sample.

Design: Endocrinologist and trainee members of the Endocrine Society of Australia were invited to participate in an anonymous 14-item survey. Of the 545 members, 147 clinicians (95 adult endocrinologists, 2 paediatric endocrinologists and 50 endocrinology trainees) responded.

Results: When presented with a scenario regarding commencement of gender-affirming hormone therapy, only 19% felt confident providing clinical care to TGD individuals. Compared to other areas of endocrinology, 75% felt less or not at all confident in commencing hormone therapy in a TGD patient. No training in transgender medicine during medical school or during their endocrinology training was reported by 96% and 60%, respectively. There were significantly higher levels of confidence in all aspects including performing a consultation in those who had previously seen a TGD patient. The desire for more training was high (91%).

Conclusions: These results highlight the shortfall in training in TGD health care amongst endocrinologists and show that prior clinical experience is associated with higher levels of confidence. Medical schools and endocrinology fellowship training programmes will need to adapt to meet the increasing demand for quality TGD health services.
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http://dx.doi.org/10.1111/cen.14143DOI Listing
March 2020

Prevalence of Autism Spectrum Disorder and Attention-Deficit Hyperactivity Disorder Amongst Individuals with Gender Dysphoria: A Systematic Review.

J Autism Dev Disord 2020 Mar;50(3):695-706

Department of Medicine (Austin Health), The University of Melbourne, Studley Road, Heidelberg, VIC, Australia.

Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) can compromise health and may be more prevalent amongst individuals with gender dysphoria (GD). Symptoms such as attention or social difficulties can impact assessment of GD, understanding of health information, and engagement in clinical care. To ensure neurodevelopmental conditions are adequately considered in gender health services, we aimed to systematically review the literature examining the prevalence of ASD and ADHD amongst individuals with GD. In this systematic review based on the PRISMA guidelines. MEDLINE and PsycINFO databases were searched for studies examining the prevalence of ASD and/or ADHD in individuals with GD or investigated the rate of GD in cohorts with ASD or ADHD. All English peer-reviewed publications were included. The search strategy identified 179 studies. After applying exclusion criteria, a total of 30 studies were identified, 22 studies which examined the prevalence of ASD or ADHD in people with GD. A further 8 studies examined the reverse; prevalence of GD in people with ASD. The few studies employing diagnostic criteria for ASD suggest a prevalence of 6-26% in transgender populations, higher than the general population, but no different from individuals attending psychiatry clinics. Few studies examine prevalence of ADHD. Low-level evidence exists to suggest a link between ASD and GD. Further population-based and controlled studies using diagnostic criteria for ASD and ADHD are required.
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http://dx.doi.org/10.1007/s10803-019-04298-1DOI Listing
March 2020

Feasibility of using a transition diabetes team to commence injectable therapies postdischarge from a tertiary hospital: a pilot, randomised controlled trial.

BMJ Open 2019 09 20;9(9):e023583. Epub 2019 Sep 20.

Endocrinology, Austin Health, Heidelberg, Victoria, Australia.

Objectives: This study aimed to investigate if the use of a transition team was feasible for patients with diabetes being discharged from hospital on injectable diabetes therapies.

Design: Pilot, randomised controlled trial.

Setting: The trial was conducted between 2014 and 2016 conjointly by a tertiary referral hospital and a community healthcare provider.

Participants: Hospital inpatients (n=105) on new injectable diabetes therapies were randomised 1:1 to transition team or standard care. The transition team received in-home diabetes education 24-48 hours postdischarge, with endocrinologist review 2-4 weeks and 16 weeks postdischarge.

Main Outcome Measures: The primary outcome was feasibility, defined by percentage of patients successfully receiving the intervention. Secondary outcomes included safety, defined by hospital readmission and emergency department presentations within 16 weeks postrandomisation, and treatment satisfaction, measured using Diabetes Treatment Satisfaction Questionnaire (DTSQ). Exploratory outcomes included length of stay (LOS) and change in haemoglobin A1c (HbA1c) throughout the study.

Results: The intervention was deemed feasible (85% (95% CI 73% to 94%)). No difference in safety between groups was detected. No difference in change in HbA1c between groups was detected (standard care median HbA1c -1.5% (IQR -3.7% to -0.2%) vs transition team median HbA1c -1.9% (IQR -3.8% to -0.2%), p=0.83). There was a trend towards reduced LOS in the transition team group (per protocol, standard care median LOS 8 (IQR 5.5-12); transition team median LOS 6 (IQR 3-12), p=0.06). There was a significant improvement in patient satisfaction in the transition team (standard care median 10.5 (IQR 8.5-16); transition team DTSQ change version median 15 (IQR 10-17.5), p=0.047), although interpretability is limited by missing data.

Conclusion: This study demonstrated that the use of a novel transition diabetes team is a feasible alternative model of care.
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http://dx.doi.org/10.1136/bmjopen-2018-023583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756454PMC
September 2019

Biomechanical Leg Muscle Function During Stair Ambulation in Men Receiving Androgen Deprivation Therapy.

J Gerontol A Biol Sci Med Sci 2020 09;75(9):1715-1722

Department of Medicine (Austin Health), Victoria.

Background: The role of testosterone in maintaining functional performance in older men remains uncertain.

Methods: We conducted a 12-month prospective, observational case-control study including 34 men newly commencing androgen deprivation therapy for prostate cancer and 29 age-matched prostate cancer controls. Video-based motion capture and ground reaction force data combined with computational musculoskeletal modeling, and data were analyzed with a linear mixed model.

Results: Compared with controls over 12 months, men receiving androgen deprivation therapy had a mean reduction in circulating testosterone from 14.1 nmol/L to 0.4 nmol/L, associated with reductions in peak knee extension torque, mean adjusted difference (MAD) -0.07 Nm/kg (95% confidence interval [CI]: -0.18, 0.04), p = .009, with a corresponding more marked decrease in quadriceps force MAD -0.11 × body weight (BW) [-0.27, 0.06], p = .045 (equating to a 9 kg force reduction for the mean body weight of 85 kg), and decreased maximal contribution of quadriceps to upward propulsion, MAD -0.47 m/s2 [-0.95, 0.02], p = .009. We observed between-group differences in several other parameters, including increased gluteus maximus force in men receiving androgen deprivation therapy, MAD 0.11 × BW [0.02, 0.20], p = .043, which may be compensatory.

Conclusions: Severe testosterone deprivation over 12 months is associated with selective deficits in lower-limb function evident with an important task of daily living.
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http://dx.doi.org/10.1093/gerona/glz169DOI Listing
September 2020

Prevalence of pre-existing dysglycaemia among inpatients with acute coronary syndrome and associations with outcomes.

Diabetes Res Clin Pract 2019 Aug 4;154:130-137. Epub 2019 Jul 4.

Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address:

Aims: We aimed to confirm the hypothesis that dysglycaemia including in the pre-diabetes range affects a majority of patients admitted with acute coronary syndrome (ACS) and is associated with worse outcomes.

Methods: In this prospective observational cohort study, consecutive inpatients aged ≥ 54 years with ACS were uniformly tested and categorised into diabetes (prior diagnosis/ HbA1c ≥ 6.5%, ≥48 mmol/mol), pre-diabetes (HbA1c 5.7-6.4%, 39-47 mmol/mol) and no diabetes (HbA1c ≤ 5.6%, ≤38 mmol/mol) groups.

Results: Over two years, 847 consecutive inpatients presented with ACS. 313 (37%) inpatients had diabetes, 312 (37%) had pre-diabetes and 222 (25%) had no diabetes. Diabetes, compared with no diabetes, was associated with higher odds of acute pulmonary oedema (APO, odds ratio, OR 2.60, p < 0.01), longer length of stay (LOS, incidence rate ratio, IRR 1.18, p = 0.02) and, 12-month ACS recurrence (OR 1.86, p = 0.046) after adjustment, while no significant associations were identified for pre-diabetes. Analysed as a continuous variable, every 1% (11 mmol/mol) increase in HbA1c was associated with increased odds of APO (OR 1.28, P = 0.002) and a longer LOS (IRR 1.05, P = 0.03).

Conclusions: The high prevalence of dysglycaemia and association with poorer clinical outcomes justifies routine HbA1c testing to identify individuals who may benefit from cardioprotective anti-hyperglycaemic agents and, lifestyle modification to prevent progression of pre-diabetes.
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http://dx.doi.org/10.1016/j.diabres.2019.07.002DOI Listing
August 2019

Position statement on the hormonal management of adult transgender and gender diverse individuals.

Med J Aust 2019 08 4;211(3):127-133. Epub 2019 Jul 4.

Austin Health, University of Melbourne, Melbourne, VIC.

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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http://dx.doi.org/10.5694/mja2.50259DOI Listing
August 2019

Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy.

Endocr Connect 2019 Jul;8(7):935-940

Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia.

Background: Oestradiol with or without an anti-androgen (cyproterone acetate or spironolactone) is commonly prescribed in transfeminine individuals who have not had orchidectomy; however, there is no evidence to guide optimal treatment choice.

Objective: We aimed to compare add-on cyproterone acetate versus spironolactone in lowering endogenous testosterone concentrations in transfeminine individuals.

Design: Retrospective cross-sectional study.

Methods: We analysed 114 transfeminine individuals who had been on oestradiol therapy for >6 months in two gender clinics in Melbourne, Australia. Total testosterone concentrations were compared between three groups; oestradiol alone (n = 21), oestradiol plus cyproterone acetate (n = 21) and oestradiol plus spironolactone (n = 38). Secondary outcomes included serum oestradiol concentration, oestradiol valerate dose, blood pressure, serum potassium, urea and creatinine.

Results: Median age was 27.0 years (22.5-45.1) and median duration of hormone therapy was 1.5 years (0.9-2.6), which was not different between groups. On univariate analysis, the cyproterone group had significantly lower total testosterone concentrations (0.8 nmol/L (0.6-1.20)) compared with the spironolactone group (2.0 nmol/L (0.9-9.4), P = 0.037) and oestradiol alone group (10.5 nmol/L (4.9-17.2), P < 0.001), which remained significant (P = 0.005) after adjustments for oestradiol concentration, dose and age. Serum urea was higher in the spironolactone group compared with the cyproterone group. No differences were observed in total daily oestradiol dose, blood pressure, serum oestradiol, potassium or creatinine.

Conclusions: The cyproterone group achieved serum total testosterone concentrations in the female reference range. As spironolactone may cause feminisation without inhibition of steroidogenesis, it is unclear which anti-androgen is more effective at feminisation. Further prospective studies are required.
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http://dx.doi.org/10.1530/EC-19-0272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612061PMC
July 2019