Relationships between insulin resistance and frailty with body composition and testosterone in men undergoing androgen deprivation therapy for prostate cancer

Cheung, Ada S; Hoermann, Rudolf; Dupuis, Philippe; Joon, Daryl Lim; Zajac, Jeffrey D; Grossmann, Mathis

doi:10.1530/eje-16-0200

Cited by 57 publications

(61 citation statements)

References 42 publications

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“…Whereas 12-month longitudinal studies have reported decreases of 5.0% to 11% in men treated with ADT [25,28,29] . Whilst these decrements appear to be greater than that of healthy older men (approximately 4.0% per year), these studies had noteworthy methodological limitations and therefore these results should be interpreted with caution.…”

Section: Muscle Strength and Powermentioning

confidence: 96%

“…In addition to decrements in lean mass and muscle CSA, the potential subsequent loss Table 2.6) [25][26][27][28][29][30] . Cross-sectional analyses…”

Section: Muscle Strength and Powermentioning

confidence: 99%

“…Interestingly, the one longitudinal study that compared handgrip strength in men treated with ADT to healthy controls observed no difference, despite men treated with ADT having demonstrated significant decrements (5.0%) when compared to PCa controls. Common limitations among these studies include the lack of comparison to both healthy and PCa controls [26][27][28][29][30] , with only one study to date including both within analyses [25] . Given the unknown degree in which men diagnosed and/or treated with non-hormonal therapies may experience indirect or direct decrements in handgrip strength (as discussed in Section 2.6.4; Figure 2.5), it is important that this population group is considered when attempting to quantify this outcome in men treated with ADT.…”

Section: Muscle Strength and Powermentioning

confidence: 99%

“…Besides the notable contribution to male cancer-related deaths [1] , the diagnosis and treatment of PCa may predispose men to a range of adverse health outcomes. One specific treatment, ADT, is often accompanied by prospective decrements in lean mass and muscle CSA [15][16][17][18][19][20][21] , increased fat mass [17][18][19][20][21][22][23] and reduced muscle strength and functional capacity [25][26][27][28][29][30][31][32][33][34] . While rates of compromise vary between trials, in part due to factors such as ADT duration and patient age, men treated with ADT tend to lose 2.0-3.6% lean mass and gain 11% fat mass per year [195] .…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, measures of muscle strength, such as via handgrip dynamometry, may decrease 5.0-11% per year in these men [25,28,29] . However, the true extent to which these outcomes may be compromised in these men in comparison to non-ADT treated individuals is unclear due largely to methodological inconsistencies in previous studies, including a lack of appropriate control group(s), differences in the measurements used to quantify muscle, fat and performance and the inability to account for different potential confounding variables such as diet and physical activity [15-23, 25-34, 36-38] .…”

Section: Introductionmentioning

confidence: 99%

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Muscle, fat and performance during androgen deprivation for prostate cancer

Owen¹

2018

Preprint

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Introduction: Prostate cancer (PCa) is one of the most frequently diagnosed male cancers worldwide. One treatment, androgen deprivation therapy (ADT), is often accompanied with a myriad of adverse effects, including those that negatively impact muscle, fat and performance outcomes. Therefore, ADT-treated men may be living longer, but are at risk of both age- and treatment-related complications. The overall aim of this thesis was to quantify outcomes of muscle, fat and performance in men treated with ADT when compared to PCa (men diagnosed with PCa, not treated with ADT) and healthy controls (men not diagnosed with PCa), and assess the feasibility of implementing a multi-component exercise program combined with protein, calcium and vitamin D supplementation (Ex+ProCaD) compared to usual care in ADT-treated men. Methods: This thesis presents two studies that form part of a larger 52-week randomised controlled trial (RCT), which examined the efficacy of Ex+ProCaD compared to usual care in men treated with ADT for PCa. The first study presented was a nested cross-sectional study performed parallel to the baseline assessment of the RCT and examined differences in muscle, fat and performance outcomes between men treated with ADT when compared to PCa and healthy controls. The second study presented examined the feasibility of implementing the first 26 weeks of the RCT. Results: The cross-sectional study showed that height, weight, body mass index and diet were similar between the three groups, but ADT-treated men were four years older and tended to be less physically active (23-30%; P=0.054). After adjusting for age and physical activity, total body fat mass was 3.3-5.0 kg (P < 0.05) greater in men treated with ADT compared to PCa controls, but there was no difference in total body and regional lean mass. When adiposity was considered, ADT-treated men had 10-12% (P < 0.05) lower appendicular lean mass adjusted for body mass index and 5.6-6.4% (P < 0.05) lower forearm percent muscle cross-sectional area compared to controls. Absolute muscle strength was similar between groups, but when expressed relative to body weight, men treated with ADT had 13-21% (P < 0.05) lower muscle strength compared to controls. Whilst only two ADT-treated men had sarcopenia, these men had a higher proportion (P < 0.001) of pre-sarcopenia when appendicular lean mass was adjusted for body mass index (42%) compared to PCa (15%) and healthy (7%) controls. Men treated with ADT had 15-36% (P < 0.05) greater storage of fat within subcutaneous depots when compared to controls, whereas visceral and intermuscular fat was similar. The majority of subcutaneous fat depots (excluding android region) were shown to be positively associated with ADT duration (P < 0.05). Forearm muscle density was shown to negatively correlate with ADT duration (P < 0.05). The RCT had a high participant retention rate (96%). Adherence was high for the supplement (mean, 92-93%) and modest for the exercise program (mean, 60%). A relatively high proportion (81%) of men in the intervention group reported an adverse event, although only 16% were confirmed to be related to the intervention and the vast majority (97%) were determined to be mild or moderate in terms of severity. Across the ten separate recruitment pathways considered, clinician referral (43%) and PCa support groups (29%) yielded the greatest proportion of enrolled participants. A total of 149 potential participants were screened, which resulted in 42 participants at the time of write up for this thesis. Among the first 28 participants to complete the 26-week intervention, 21-50% were unable to complete at least one measure of muscle strength due to pre-existing comorbidities. Data from the initial 28 participants tended to show that when compared to usual care, Ex+ProCaD led to net improvements in lean mass (0.2-1.4 kg), fat mass (-0.1 to -0.9 kg), muscle strength (8.0-19%), functional muscle power (8.6%) and functional capacity (12-14%). Conclusions: The following key themes emerged from this thesis and may be used to guide clinical practice guidelines and future research: 1) Men treated with ADT for PCa had greater amounts of fat when compared to non-ADT counterparts, 2) Current definitions of sarcopenia and sarcopenic obesity were limited in men treated with ADT for PCa, 3) The greater amounts of fat observed in men treated with ADT for PCa tended to be stored in subcutaneous depots and supersede age-related plateaus/losses, 4) The recruitment of men treated with ADT for PCa into a lifestyle intervention was challenging, and 5) Men treated with ADT for PCa tended to respond positively to a multi-modal exercise training combined with multi-nutrient supplementation.

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Section: Muscle Strength and Powermentioning

confidence: 96%

“…In addition to decrements in lean mass and muscle CSA, the potential subsequent loss Table 2.6) [25][26][27][28][29][30] . Cross-sectional analyses…”

Section: Muscle Strength and Powermentioning

confidence: 99%

Section: Muscle Strength and Powermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Muscle, fat and performance during androgen deprivation for prostate cancer

Owen¹

2018

Preprint

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Examining the associations between testosterone and biomarkers as men age

Smith

Bekele

Lopresti

et al. 2023

American J Hum Biol

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ObjectivesTestosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone‐binding globulin (SHBG), using a large nationally‐representative data set (National Health and Nutrition Examination Survey; NHANES).MethodsNHANES is a cross‐sectional survey, physical examination, and laboratory evaluation of a nationally‐representative sample of a non‐institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013–2014 and NHANES 2015–2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA‐IR), insulin, glucose, and age.ResultsAn overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA‐IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA‐IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre‐diabetic HOMA‐IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables.ConclusionThe results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.

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