Medicine (Austin & Northern Health) - Research Publications

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    Testosterone levels increase in association with recovery from acute fracture in men
    Cheung, AS ; Baqar, S ; Sia, R ; Hoermann, R ; Iuliano-Burns, S ; Vu, TDT ; Chiang, C ; Hamilton, EJ ; Gianatti, E ; Seeman, E ; Zajac, JD ; Grossmann, M (SPRINGER LONDON LTD, 2014-08)
    UNLABELLED: In this longitudinal case-control study, acute fracture was associated with low serum testosterone, which was transient in 43% of men. While assessment of gonadal status is part of the assessment of bone fragility, measurement of testosterone in the early period after fracture may overestimate the prevalence of androgen deficiency. INTRODUCTION: Measurement of circulating testosterone is recommended in the evaluation of bone fragility in men. Since acute illness can transiently decrease circulating testosterone, we quantified the association of acute fracture and serum testosterone levels. METHODS: A case-control study was conducted involving 240 men with a radiologically confirmed minimal trauma fracture presenting to a tertiary referral hospital and 89 age-matched men without a history of minimal trauma fracture serving as controls. Follow-up testosterone levels 6 months after baseline were available for 98 cases and 27 controls. Results were expressed as the median and interquartile (IQR) range. RESULTS: Compared to controls, cases had lower total testosterone [TT, 7.2 (3.5, 10.8) vs 13.6 (10.9, 17.1) nmol/L, p < 0.001]. The 143 cases treated as inpatients had lower testosterone levels than the 97 cases treated as outpatients [TT 4.7 (2.3, 8.1) vs 10.3 (7.5, 12.7) nmol/L, p < 0.001]. Group differences in calculated free testosterone (cFT) were comparable to the group differences in TT. At follow-up, in 98 cases, median TT increased from 6.5 nmol/L (3.2, 8.5) to 9.6 nmol/L (6.9, 12.0) p < 0.0001, and SHBG remained unchanged. Of cases with low testosterone, 43% with TT <10 nmol/L and/or cFT <230 pmol/L at presentation were reclassified as androgen sufficient at follow-up. TT was unchanged in the controls. CONCLUSIONS: Low testosterone levels in men presenting with an acute fracture may, at least in part, be due to an acute, fracture-associated, stress response. To avoid over diagnosis, evaluation for testosterone deficiency should be deferred until recovery from the acute event.
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    Effect of Testosterone Treatment on Glucose Metabolism in Men With Type 2 Diabetes: A Randomized Controlled Trial
    Gianatti, EJ ; Dupuis, P ; Hoermann, R ; Strauss, BJ ; Wentworth, JM ; Zajac, JD ; Grossmann, M (AMER DIABETES ASSOC, 2014-08)
    OBJECTIVE: To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. RESEARCH DESIGN AND METHODS: We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35-70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). RESULTS: Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo -0.08 [95% CI -0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0-0.7]; P = 0.05), despite a decrease in fat mass (MAD -2.38 kg [-3.10 to -1.66]; P < 0.001) and an increase in lean mass (MAD 2.08 kg [1.52-2.64]; P < 0.001). Testosterone therapy reduced subcutaneous (MAD -320 cm(3) [-477 to -163]; P < 0.001) but not visceral abdominal adipose tissue (MAD 140 cm(3) [-89 to 369]; P = 0.90). CONCLUSIONS: Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D.
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    Effect of Testosterone Treatment on Constitutional and Sexual Symptoms in Men With Type 2 Diabetes in a Randomized, Placebo-Controlled Clinical Trial
    Gianatti, EJ ; Dupuis, P ; Hoermann, R ; Zajac, JD ; Grossmann, M (ENDOCRINE SOC, 2014-10)
    OBJECTIVE: The objective of the study was to assess the effect of T treatment on constitutional and sexual symptoms in men with type 2 diabetes (T2D). DESIGN: This was a randomized double-blind, parallel, placebo-controlled trial. SETTING: The study was conducted at a tertiary referral center. PATIENTS: Men aged 35-70 years with T2D, a hemoglobin A1c less than 8.5%, and a total T level less than 12.0 nmol/L (346 ng/dL) with mild to moderate aging male symptoms and erectile dysfunction. INTERVENTION: Eighty-eight participants were randomly assigned to 40 weeks of im T undecanoate (n = 45) or matching placebo (n = 43). MAIN OUTCOME MEASURES: Constitutional symptoms using the aging male symptoms (AMS) score, sexual desire (question 17 AMS score), and erectile function (International Index of Erectile Function-5). RESULTS: T treatment did not substantially improve aging male symptoms [mean adjusted difference (MAD) in change over 40 weeks across the T and placebo groups in AMS total score, -0.9 (95% confidence interval [CI] -4.1, 2.2), P = .67] or sexual desire [MAD in question 17 AMS, -0.3 (95% CI -0.8, 0.2), P = .17]. Although compared with placebo, erectile function in men assigned to T was reduced [MAD in International Index of Erectile Function abridged version 5, -2.0 (95% CI -3.4, -0.6), P < .02], there was no significant difference between baseline and 40-week International Index of Erectile Function abridged version 5 scores if both groups were analyzed separately. At baseline, symptoms were worse in men with depression and microvascular complications but did not correlate with T levels. CONCLUSIONS: In this trial, T treatment did not substantially improve constitutional or sexual symptoms in obese, aging men with T2D with mild to moderate symptoms and modest reduction in T levels typical for the vast majority of such men.
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    Measuring thyroid peroxidase antibodies on the day nulliparous women present for management of miscarriage: a descriptive cohort study
    Grossmann, M ; Hoermann, R ; Francis, C ; Hamilton, EJ ; Tint, A ; Kaitu'u-Lino, T ; Kuswanto, K ; Lappas, M ; Sikaris, K ; Zajac, JD ; Permezel, M ; Tong, S (BIOMED CENTRAL LTD, 2013-05-14)
    BACKGROUND: There has been recent evidence suggesting the presence of anti-thyroid peroxidase antibodies (TPOAb) increases the risk of miscarriage, and levothyroxine can rescue miscarriages associated with TPOAb. We propose the most clinically pragmatic cohort to screen for TPOAb are women presenting for management of a missed miscarriage and have never birthed a liveborn. We measured serum TPOAb among nulliparous women presenting for management of miscarriage, and compared levels with women who have had 2 or more livebirths (and never miscarried). Given its potential role in immunomodulation, we also measured Vitamin D levels. METHODS: We performed a prospective descriptive cohort study at a tertiary hospital (Mercy Hospital for Women, Victoria, Australia). We measured TPOAb and Vitamin D levels in serum obtained from 118 nulliparous women presenting for management of miscarriage, and 162 controls with 2 or more livebirths (and no miscarriages). Controls were selected from a serum biobank prospectively collected in the first trimester at the same hospital. RESULTS: Nulliparous women with 1 or more miscarriages had higher thyroid peroxidase antibody (TPOAb) levels than those with 2 or more livebirths; TPOAb in miscarriage group was 0.3 mIU/L (interquartile range [IR]: 0.2-0.7) vs 0.2 mIU/L among controls (IR 0.0-0.5; p < 0.0001). We confirmed TPOAb levels were not correlated with serum human chorionic gonadotrophin (hCG) concentrations in either the miscarriage or control groups. In contrast, thyroid stimulating hormone, fT3 and fT4 levels (thyroid hormones) either trended towards a correlation, or were significantly correlated with serum hCG levels in the two groups. Of the entire cohort that was predominantly caucasian, only 12% were Vitamin D sufficient. Low Vitamin D levels were not associated with miscarriage. CONCLUSIONS: We have confirmed the association between miscarriage and increased TPOAb levels. Furthermore, it appears TPOAb levels in maternal blood are not influenced by serum hCG levels. Therefore, we propose the day nulliparous women present for management for miscarriage is a clinically relevant, and pragmatic time to screen for TPOAb.
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    Obesity and age as dominant correlates of low testosterone in men irrespective of diabetes status
    Fui, MNT ; Hoermann, R ; Cheung, AS ; Gianatti, EJ ; Zajac, JD ; Grossmann, M (WILEY, 2013-11)
    Although men with type 2 diabetes (T2D) frequently have lowered testosterone levels, it is not well established whether this is ascribable to the diabetic state per se, or because of other factors, such as obesity. Our objective was to determine the prevalence and correlates of low testosterone in middle-aged men with diabetes. We conducted a cross-sectional study in 240 men including 80 men with type 1 diabetes (T1D), 80 men with T2D and 80 men without diabetes. Prevalence of a total testosterone ≤8 nmol/L was low, occurring in none of the men with T1D, 6.2% of men with T2D and 2.5% of men without diabetes. Men with T1D had higher testosterone levels compared with men without diabetes (p < 0.001), even after adjustment for body mass index (BMI) and age (p < 0.02). While men with T2D had lower testosterone compared with controls (p = 0.03), this was no longer significant when BMI and age were taken into account (p = 0.16). In the entire cohort, TT remained inversely associated with BMI independent of age, sex hormone-binding globulin and diabetic status (p = 0.01), whereas calculated free testosterone (cFT) was independently and inversely associated with age (p < 0.001), but not with BMI (p = 0.47). These results suggest that marked reductions in circulating testosterone are uncommon in middle-aged men with diabetes. Increasing BMI and age are dominant drivers of lowered total and cFT, respectively, independent of the presence or absence of diabetes.
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    Cardiovascular risk and bone loss in men undergoing androgen deprivation therapy for non-metastatic prostate cancer: implementation of standardized management guidelines
    Cheung, AS ; Pattison, D ; Bretherton, I ; Hoermann, R ; Joon, DL ; Ho, E ; Jenkins, T ; Hamilton, EJ ; Bate, K ; Chan, I ; Zajac, JD ; Grossmann, M (WILEY, 2013-07)
    Our objective was to evaluate the effectiveness of implementing standardized guidelines to mitigate metabolic and bone side effects of androgen deprivation therapy (ADT) in men with non-metastatic prostate cancer. We conducted a 2-year prospective cohort study at a tertiary referral teaching hospital. Overall, 236 men (mean age 69.8 ± 7.1) commencing ADT for non-metastatic prostate cancer attended a baseline clinic visit between 2007 and 2011, and 153 men were eligible for follow-up after 2 years of continuous ADT. Of these, 113 men had data available for analysis at 2 years. At baseline, 87% of the men were overweight or obese, 61% had hypertension, 56% had hypercholesterolaemia, 27% prior cardiovascular disease, 11% osteoporosis and 40% osteopaenia. After 2 years of ADT, there was an increase in waist circumference (+2.8 ± 6.3 cm, p = 0.002), and, in men without diabetes, in HbA1c (+0.13 ± 0.34%, p = 0.019). Despite this, due to treatment, there were significant reductions in total cholesterol (-0.35 ± 1.00 mmol/L, p < 0.001), and blood pressure (systolic -7.6 ± 19.3 mmHg; diastolic -4.7 ± 11.6 mmHg, p < 0.001). After 2 years, men not receiving anti-resorptive therapy experienced a significant decline in lumbar spine (-0.042 ± 0.134 g/cm(2) , p = 0.012) and total hip bone mineral density (BMD) (-0.026 ± 0.036 g/cm(2) , p < 0.001), whereas bisphosphonate treatment maintained stable BMD. Prevalence of anaemia increased from 13.8 to 32.5%. Older age independently predicted a greater drop in haemoglobin (p = 0.005). We conclude that a structured approach to assess and treat men undergoing ADT effectively improves cardiovascular risk factors and prevents bone decay. Larger studies are needed to determine effects on cardiovascular outcomes, fracture prevention and survival.