Medicine (Austin & Northern Health) - Research Publications

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    Met and unmet need for medical gender affirmation in the Australian non-binary community
    Zwickl, S ; Ruggles, T ; Sheahan, S ; Murray, J ; Grace, J ; Ginger, A ; Wong, AFQ ; Cheung, AS (TAYLOR & FRANCIS INC, 2024-01-01)
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    The Impact of Gender-Affirming Hormone Therapy on Physical Performance
    Cheung, AS ; Zwickl, S ; Miller, K ; Nolan, BJ ; Wong, AFQ ; Jones, P ; Eynon, N (ENDOCRINE SOC, 2024-01-18)
    CONTEXT: The inclusion of transgender people in elite sport has been a topic of debate. This narrative review examines the impact of gender-affirming hormone therapy (GAHT) on physical performance, muscle strength, and markers of endurance. EVIDENCE ACQUISITION: MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT), and physical performance outcomes. EVIDENCE SYNTHESIS: Existing literature comprises cross-sectional or small uncontrolled longitudinal studies of short duration. In nonathletic trans men starting testosterone therapy, within 1 year, muscle mass and strength increased and, by 3 years, physical performance (push-ups, sit-ups, run time) improved to the level of cisgender men. In nonathletic trans women, feminizing hormone therapy increased fat mass by approximately 30% and decreased muscle mass by approximately 5% after 12 months, and steadily declined beyond 3 years. While absolute lean mass remains higher in trans women, relative percentage lean mass and fat mass (and muscle strength corrected for lean mass), hemoglobin, and VO2 peak corrected for weight was no different to cisgender women. After 2 years of GAHT, no advantage was observed for physical performance measured by running time or in trans women. By 4 years, there was no advantage in sit-ups. While push-up performance declined in trans women, a statistical advantage remained relative to cisgender women. CONCLUSION: Limited evidence suggests that physical performance of nonathletic trans people who have undergone GAHT for at least 2 years approaches that of cisgender controls. Further controlled longitudinal research is needed in trans athletes and nonathletes.
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    Implications of gender-affirming endocrine care for sports participation
    Moreland, E ; Cheung, AS ; Hiam, D ; Nolan, BJ ; Landen, S ; Jacques, M ; Eynon, N ; Jones, P (SAGE PUBLICATIONS LTD, 2023-06)
    Many transgender (trans) individuals utilize gender-affirming hormone therapy (GAHT) to promote changes in secondary sex characteristics to affirm their gender. Participation rates of trans people in sport are exceedingly low, yet given high rates of depression and increased cardiovascular risk, the potential benefits of sports participation are great. In this review, we provide an overview of the evidence surrounding the effects of GAHT on multiple performance-related phenotypes, as well as current limitations. Whilst data is clear that there are differences between males and females, there is a lack of quality evidence assessing the impact of GAHT on athletic performance. Twelve months of GAHT leads to testosterone concentrations that align with reference ranges of the affirmed gender. Feminizing GAHT in trans women increases fat mass and decreases lean mass, with opposite effects observed in trans men with masculinizing GAHT. In trans men, an increase in muscle strength and athletic performance is observed. In trans women, muscle strength is shown to decrease or not change following 12 months of GAHT. Haemoglobin, a measure of oxygen transport, changes to that of the affirmed gender within 6 months of GAHT, with very limited data to suggest possible reductions in maximal oxygen uptake as a result of feminizing GAHT. Current limitations of this field include a lack of long-term studies, adequate group comparisons and adjustment for confounding factors (e.g. height and lean body mass), and small sample sizes. There also remains limited data on endurance, cardiac or respiratory function, with further longitudinal studies on GAHT needed to address current limitations and provide more robust data to inform inclusive and fair sporting programmes, policies and guidelines.
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    Effect of gender-affirming hormone therapy on hair growth: a systematic review of the literature
    Tang, GT ; Zwickl, S ; Sinclair, R ; Zajac, JD ; Cheung, AS (OXFORD UNIV PRESS, 2023-09-19)
    Gender-affirming hormone therapy (GAHT) leads to changes in body composition, secondary sex characteristics and in the distribution and pattern of hair growth. Transgender individuals undergoing GAHT may experience altered hair growth patterns that may be affirming and desirable, or undesirable with a subsequent impact on their quality of life. Given increasing numbers of transgender individuals commencing GAHT worldwide and the clinical relevance of the impact of GAHT on hair growth, we systematically reviewed the existing literature on the impact of GAHT on hair changes and androgenic alopecia (AGA). The majority of studies used grading schemes or subjective measures of hair changes based on patient or investigator's examination. Very few studies used objective quantitative measures of hair parameters but demonstrated statistically significant changes in hair growth length, diameter and density. Feminizing GAHT with estradiol and/or antiandrogens in transgender women may reduce facial and body hair growth and also can improve AGA. Masculinizing GAHT with testosterone in transgender men may increase facial and body hair growth as well as induce or accelerate AGA. The impact of GAHT on hair growth may not align with a transgender person's hair growth goals and specific treatment for AGA and/or hirsutism may be sought. Further research on how GAHT affects hair growth is required.
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    Estradiol Concentrations and Wellbeing in Trans People Using Estradiol Hormone Therapy
    Ginger, A ; Zwickl, S ; Angus, LM ; Leemaqz, SY ; Cook, T ; Wong, AFQ ; Cheung, AS (MARY ANN LIEBERT, INC, 2023-01-01)
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    Early Access to Testosterone Therapy in Transgender and Gender-Diverse Adults Seeking Masculinization A Randomized Clinical Trial
    Nolan, BJ ; Zwickl, S ; Locke, P ; Zajac, JD ; Cheung, AS (JAMA Network, 2023-09-07)
    IMPORTANCE: Testosterone treatment is a necessary component of care for some transgender and gender-diverse individuals. Observational studies have reported associations between commencement of gender-affirming hormone therapy and improvements in gender dysphoria and depression, but there is a lack of data from randomized clinical trials. OBJECTIVE: To assess the effect of testosterone therapy compared with no treatment on gender dysphoria, depression, and suicidality in transgender and gender-diverse adults seeking masculinization. DESIGN, SETTING, AND PARTICIPANTS: A 3-month open-label randomized clinical trial was conducted at endocrinology outpatient clinics and primary care clinics specializing in transgender and gender-diverse health in Melbourne, Australia, from November 1, 2021, to July 22, 2022. Participants included transgender and gender-diverse adults aged 18 to 70 years seeking initiation of testosterone therapy. INTERVENTIONS: Immediate initiation of testosterone commencement (intervention group) or no treatment (standard care waiting list of 3 months before commencement). This design ensured no individuals would be waiting longer than the time to standard care. MAIN OUTCOMES AND MEASURES: The primary outcome was gender dysphoria, as measured by the Gender Preoccupation and Stability Questionnaire. Secondary outcomes included the Patient Health Questionnaire-9 (PHQ-9) to assess depression and the Suicidal Ideation Attributes Scale (SIDAS) to assess suicidality. Questionnaires were undertaken at 0 and 3 months. The evaluable cohort was analyzed. RESULTS: Sixty-four transgender and gender-diverse adults (median [IQR] age, 22.5 [20-27] years) were randomized. Compared with standard care, the intervention group had a decrease in gender dysphoria (mean difference, -7.2 points; 95% CI, -8.3 to -6.1 points; P < .001), a clinically significant decrease in depression (ie, change in score of 5 points on PHQ-9; mean difference, -5.6 points; 95% CI, -6.8 to -4.4 points; P < .001), and a significant decrease in suicidality (mean difference in SIDAS score, -6.5 points; 95% CI, -8.2 to -4.8 points; P < .001). Resolution of suicidality assessed by PHQ-9 item 9 occurred in 11 individuals (52%) with immediate testosterone commencement compared with 1 (5%) receiving standard care (P = .002). Seven individuals reported injection site pain/discomfort and 1 individual reported a transient headache 24 hours following intramuscular administration of testosterone undecanoate. No individual developed polycythemia. CONCLUSIONS AND RELEVANCE: In this open-label randomized clinical trial of testosterone therapy in transgender and gender-diverse adults, immediate testosterone compared with no treatment significantly reduced gender dysphoria, depression, and suicidality in transgender and gender-diverse individuals desiring testosterone therapy. TRIAL REGISTRATION: ANZCTR Identifier: ACTRN1262100016864.
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    Dermatological considerations for transgender and gender diverse patients: An Australian perspective
    Gu, Y ; Tang, GT ; Cheung, AS-Z ; Sebaratnam, DF (WILEY, 2024-02)
    Transgender and gender diverse (TGD) individuals are a group that experiences significant health disparities. In the multidisciplinary management of TGD patients, dermatologists may participate in managing skin- and hair-related issues which contribute to gender affirmation and to the cutaneous sequelae of gender-affirming hormone therapy. This review aims to highlight the unique needs of TGD patients, particularly from the perspective of Australian dermatologists. We review appropriate terminology critical for TGD care, gender affirmation in the Australian healthcare landscape, dermatological considerations for TGD patients and considerations for management.
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    Prevalence of polycythaemia with different formulations of testosterone therapy in transmasculine individuals
    Nolan, BJ ; Leemaqz, SY ; Ooi, O ; Cundill, P ; Silberstein, N ; Locke, P ; Grossmann, M ; Zajac, JD ; Cheung, AS (WILEY, 2021-06)
    BACKGROUND: Masculinising hormone therapy with testosterone is used to align an individual's physical characteristics with his or her 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. A total of 180 individuals who were on testosterone therapy for >6 months was included. Groups included those receiving: (i) intramuscular testosterone undecanoate (n = 125); (ii) intramuscular testosterone enantate (n = 31); or (iii) 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 of 37.7 (24.2) months; 27% were smokers. There was no difference between groups in serum total testosterone concentration measured. While there was no difference between groups in haematocrit, there was a higher proportion of patients with polycythaemia 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 testosterone, 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.
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    Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial
    Russell, N ; Ghasem-Zadeh, A ; Hoermann, R ; Cheung, AS ; Zajac, JD ; Shore-Lorenti, C ; Ebeling, PR ; Handelsman, DJ ; Grossmann, M (BIOSCIENTIFICA LTD, 2022-08)
    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: This study is a 6-month randomized, placebo-controlled trial with the hypothesis that E2 would slow the decline of volumetric bone mineral density (vBMD) and bone microstructure, maintain areal bone mineral density (aBMD), and reduce bone remodelling. METHODS: 78 participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel daily or matched placebo. The outcome measures were vBMD and microarchitecture at the distal tibia and distal radius by high-resolution peripheral quantitative CT, aBMD at the spine and hip by dual-energy x-ray absorptiometry, and serum bone remodelling markers. RESULTS: For the primary endpoint, total vBMD at the distal tibia, there was no significant difference between groups, mean adjusted difference (MAD) 2.0 mgHA/cm3 (95% CI: -0.8 to 4.8), P = 0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8 mgHA/cm3 (95% CI: 4.5 to 25.0), P = 0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250 N (95% CI: 36 to 465), P = 0.02, and radius, MAD 193 N (95% CI: 65 to 320), P = 0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02 g/cm2 (95% CI: 0.01 to 0.03), P = 0.01, and ultra-distal radius, MAD 0.01 g/cm2 (95% CI: 0.00 to 0.02), P = 0.01, and reduced serum bone remodelling markers. CONCLUSION: Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.