Effects of androgens on glucose metabolism

Umapathysivam, Mahesh M.; Grossmann, Mathis; Wittert, Gary

doi:10.1016/j.beem.2022.101654

Cited by 8 publications

(6 citation statements)

References 78 publications

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“…In men, it has been observed that testosterone levels decrease as weight gain occurs. This correlation is influenced by various intricate interactions involving obesity, insulin resistance, and the hypothalamic-pituitary-testicular axis ( Umapathysivam, Grossmann & Wittert, 2022 ). In this study, no significant correlation was found between hyperglycemia and initial testosterone levels.…”

Section: Discussionmentioning

confidence: 99%

Effect of metabolic syndrome on testosterone levels in patients with metastatic prostate cancer: a real-world retrospective study

Zhuo,

Yao,

Mei

et al. 2024

PeerJ

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Background Metabolic syndrome (MetS) has been shown to have a negative impact on prostate cancer (PCa). However, there is limited research on the effects of MetS on testosterone levels in metastatic prostate cancer (mPCa). Objective This study aims to investigate the influence of MetS, its individual components, and composite metabolic score on the prognosis of mPCa patients, as well as the impact on testosterone levels. Additionally, it seeks to identify MetS-related risk factors that could impact the time of decline in testosterone levels among mPCa patients. Methods A total of 212 patients with mPCa were included in the study. The study included 94 patients in the Non-MetS group and 118 patients in the combined MetS group. To analyze the relationship between MetS and testosterone levels in patients with mPCa. Additionally, the study aimed to identify independent risk factors that affect the time for testosterone levels decline through multifactor logistic regression analysis. Survival curves were plotted by the Kaplan-Meier method. Results Compared to the Non-MetS group, the combined MetS group had a higher proportion of patients with high tumor burden, T stage ≥ 4, and Gleason score ≥ 8 points (P < 0.05). Patients in the combined MetS group also had higher lowest testosterone values and it took longer for their testosterone to reach the lowest level (P < 0.05). The median progression-free survival (PFS) time for patients in the Non-MetS group was 21 months, while for those in the combined MetS group it was 18 months (P = 0.001). Additionally, the median overall survival (OS) time for the Non-MetS group was 62 months, whereas for the combined MetS group it was 38 months (P < 0.001). The median PFS for patients with a composite metabolic score of 0–2 points was 21 months, 3 points was 18 months, and 4–5 points was 15 months (P = 0.002). The median OS was 62 months, 42 months, and 29 months respectively (P < 0.001). MetS was found to be an independent risk factor for testosterone levels falling to the lowest value for more than 6 months. The risk of testosterone levels falling to the lowest value for more than 6 months in patients with MetS was 2.157 times higher than that of patients with Non-MetS group (P = 0.031). Patients with hyperglycemia had a significantly higher lowest values of testosterone (P = 0.015). Additionally, patients with a BMI ≥ 25 kg/m2 exhibited lower initial testosterone levels (P = 0.007). Furthermore, patients with TG ≥ 1.7 mmol/L experienced a longer time for testosterone levels to drop to the nadir (P = 0.023). The lowest value of testosterone in the group with a composite metabolic score of 3 or 4–5 was higher than that in the 0–2 group, and the time required for testosterone levels to decrease to the lowest value was also longer (P < 0.05). Conclusion When monitoring testosterone levels in mPCa patients, it is important to consider the impact of MetS and its components, and make timely adjustments to individualized treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Effect of metabolic syndrome on testosterone levels in patients with metastatic prostate cancer: a real-world retrospective study

Zhuo,

Yao,

Mei

et al. 2024

PeerJ

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“…Ultimately, post-pubescent cis males possess several significant anthropometric and physiological differences ( Table 1 ) compared to cis females, which correspond to a post-pubescent divergence in athletic performance between males and females [ 55 , 58 ], which this review will focus on. However, there are other factors such as, glucose utilisation [ 59 , 60 ], body fat distribution [ 61 ], lipid metabolism [ 60 ], energy balance [ 60 ], oestrogen levels [ 54 ], and skeletal muscle fibre type [ 62 ], all of which can affect athletic performance and are all affected by testosterone levels.…”

Section: Physiological Cisgender Male Vs Cisgender Female Differencesmentioning

confidence: 99%

The Participation of Trans Women in Competitive Fencing and Implications on Fairness: A Physiological Perspective Narrative Review

Tidmas,

Halsted,

Cohen

et al. 2023

Sports

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Debate has surrounded whether the participation of trans women in female sporting categories is fair, specifically the retained male physiological advantage due to increased testosterone compared to cisgender females. Recently, individual sporting organisations have been investigating and assessing policies regarding trans women athlete participation in female categories, resulting in several banning participation. This review aims to discuss the scientific evidence and provide appropriate guidance for the inclusion of trans women in elite competitive female fencing categories. Fencing is an intermittent sport, where competitions can span 1 to 3 days. The lunge is the most common movement used to attack opponents, where a successful hit relies on the speed of the action. Male puberty induced increased circulating testosterone promotes a greater stature, cardiovascular function, muscle mass, and strength compared to cisgender females, culminating in a ~12–40% sport performance advantage. Elite cisgender male fencers perform significantly higher, ~17–30%, jump heights and leg power measures compared to elite cisgender female fencers, resulting in faster lunges. Trans women receiving androgen-suppression therapy for 12 months showed significant reductions in strength, lean body mass, and muscle surface area, but even after 36 months, the measurements of these three indices remained above those for cisgender females. Previous male muscle mass and strength can be retained through continuation of resistance training. The literature reviewed shows that there is a retained physiological advantage for trans women who have undergone male puberty when participating in the elite competitive female fencing category. A proposed solution of an open or third gender category for elite fencing competition promotes fair competition, while allowing trans women to compete in their chosen sport.

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“…All testosterone assays measure total testosterone which predominantly reflects SHBG-bound testosterone, and therefore, if SHBG decreases, this will be reflected in a decrease in total testosterone concentration (Gleicher et al 2020, Kim et al 2020, Zhou et al 2020. The extent to which, and under what circumstances, there are direct defects of excess adipose tissue on the regulation of the hypothalamic-pituitary-testicular (HPT) axis is not completely resolved, but there is some evidence for mediation by hypothalamic leptin resistance, central effects of inflammatory cytokines and inhibitory effects of increased oxidised low-density lipoprotein, adenosine and dysregulated iron metabolism on Leydig cell function in the testis (Umapathysivam et al 2022).…”

Section: Waist Circumference To Assess Obesitymentioning

confidence: 99%

“…The apparent decrease in testosterone seen in unselected middle aged and older men reflects obesity and the accumulation of chronic conditions (Shi et al 2013), for example, cardiovascular disease (Regadera et al 1985) and depression (Finkelstein et al 2013, Shi et al 2013, medication use (most commonly opioids), health-related behaviours (e.g. excessive alcohol consumption) and psychosocial factors (Wittert & Grossmann 2022) rather than chronological ageing in itself. However, beyond the age of 70 years, declining testosterone concentrations in unselected men with co-morbidities are accompanied by increases in LH, suggesting possibly impaired Leydig cell function (Yeap et al 2018).…”

Section: Introduction Testosterone Obesity and Male Ageingmentioning

confidence: 99%

“…However, beyond the age of 70 years, declining testosterone concentrations in unselected men with co-morbidities are accompanied by increases in LH, suggesting possibly impaired Leydig cell function (Yeap et al 2018). The obesity phenotype associated with a decrease in serum testosterone concentration in middle to older aged men is associated with a reduction serum SHBG with mid-normal serum LH and FSH and is characterised by an accumulation of visceral adipose tissue associated with insulin resistance, aberrant glucose metabolism and dyslipidaemia as features of the metabolic syndrome (Umapathysivam et al 2022). The proportionate fall in serum testosterone and sex hormone binding globulin (SHBG) concentrations under these circumstances is inherently reversible with weight loss (Grossmann 2018) and does not demonstrate androgen deficiency.…”

Section: Introduction Testosterone Obesity and Male Ageingmentioning

confidence: 99%

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Testosterone and type 2 diabetes prevention: translational lessons from the T4DM study

Wittert

Grossmann

Yeap

et al. 2023

Journal of Endocrinology

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Testosterone acting via the androgen receptor, and via aromatisation to oestradiol, an activator of the oestrogen receptor, plays key roles in adipose tissue, bone, and skeletal muscle biology. This is reflected in epidemiological studies associating obesity and disordered glucose metabolism with lower serum testosterone concentrations and an increased risk of type 2 diabetes (T2D) in men. Testosterone also modulates erythrocytosis and vascular endothelial and smooth muscle cell function, with potential impacts on haematocrit and the cardiovascular system. The Testosterone for the Prevention of Type 2 Diabetes (T4DM) study enrolled men aged 50 years and over with a waist circumference of 95cm or over, impaired glucose tolerance or newly diagnosed T2D, and a serum testosterone concentration (as measured by chemiluminescence immunoassay) <14.0 nmol/L. The study reported that 2 years treatment with testosterone undecanoate 1000mg, administered 3-monthly intramuscularly, on the background of a lifestyle program, reduced the likelihood of T2D diagnosis by 40% compared to placebo. This effect was accompanied by a decrease in fasting serum glucose, and associated with favourable changes in body composition, hand grip strength, bone mineral density and skeletal microarchitecture, but not in HbA1c, a red blood cell-dependent measure of glycaemic control. There was no signal for cardiovascular adverse events. With the objective of informing translational science and future directions, this commentary discusses mechanistic studies underpinning the rationale for T4DM, and translational implications of the key outcomes relating to glycaemia, and body composition, together with effects on erythrocytosis, and cardiovascular risk and slow recovery of the hypothalamo-pituitary-testicular axis.

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Effects of androgens on glucose metabolism

Cited by 8 publications

References 78 publications

Effect of metabolic syndrome on testosterone levels in patients with metastatic prostate cancer: a real-world retrospective study

Effect of metabolic syndrome on testosterone levels in patients with metastatic prostate cancer: a real-world retrospective study

The Participation of Trans Women in Competitive Fencing and Implications on Fairness: A Physiological Perspective Narrative Review

Testosterone and type 2 diabetes prevention: translational lessons from the T4DM study

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