-
1.
Social cognitive outcomes are associated with improvements in mobility performance following lifestyle intervention in prostate cancer patients undergoing androgen deprivation therapy.
Chaplow, ZL, Lucas, AR, Grainger, E, Simpson, C, Fairman, CM, DeScenza, VR, Bowman, J, Clinton, SK, Focht, BC
PloS one. 2022;(1):e0263136
Abstract
OBJECTIVE To compare the effects of an exercise and dietary intervention with those of standard-of-care management upon change in lift and carry performance and mobility-related self-efficacy beliefs and explore associations in prostate cancer patients undergoing androgen deprivation therapy. METHODS 32 prostate cancer patients (M age = 66.2 years; SD = 7.8) undergoing androgen deprivation therapy were randomly assigned to a 3-month exercise and dietary lifestyle intervention (n = 16) or standard-of-care management (n = 16). Outcome assessments were obtained at baseline, 2- and 3-month follow-up. RESULTS The lifestyle intervention resulted in significantly greater improvements in lift and carry performance (p = 0.01) at 2 Months (d = 1.01; p < 0.01) and 3 Months (d = 0.95; p < 0.01) and superior improvements in mobility-related self-efficacy at 2 Months (d = 0.38) and 3 Months (d = 0.58) relative to standard-of-care. Mobility-related self-efficacy (r = -.66; p = 0.006) and satisfaction with function (r = -.63; p = 0.01) were significantly correlated with lift and carry performance at 3 Months. CONCLUSIONS The exercise and dietary lifestyle intervention yielded superior improvements in lift and carry performance and mobility-related self-efficacy relative to standard-of-care and key social cognitive outcomes were associated with more favorable mobility performance.
-
2.
Mediterranean-style dietary pattern improves cancer-related fatigue and quality of life in men with prostate cancer treated with androgen deprivation therapy: A pilot randomised control trial.
Baguley, BJ, Skinner, TL, Jenkins, DG, Wright, ORL
Clinical nutrition (Edinburgh, Scotland). 2021;(1):245-254
Abstract
BACKGROUND & AIMS Cancer-related fatigue (CRF) is a prevalent and persistent symptom from androgen deprivation therapy (ADT) in prostate cancer. The Mediterranean-style dietary pattern (MED-diet) offers a plausible mechanism to mitigate CRF through reducing inflammation and improving body composition. This study aimed to evaluate the effects of a 12-week MED-diet, compared to usual care, on CRF and quality of life in men with prostate cancer treated with ADT. METHODS Twenty-three men (65.9 ± 7.8 years; body mass index: 29.6 ± 2.7 kg/m2; ADT duration: 33.8 ± 35.6 months) receiving ADT for ≥3 months were randomly assigned (1:1) to 12-weeks of usual care or the MED-diet involving six individualised nutrition consults. Primary outcomes included CRF [Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (FACIT-F) and quality of life [FACIT-General (FACIT-G)], secondary outcomes included body mass/composition and interleukin (IL)-6 and IL-8 concentrations measured at baseline, 8-weeks and 12 weeks. Intervention feasibility was measured by intervention safety, study completion rate, consult attendance, and adherence to the MED-diet through the Mediterranean-diet adherence screener (MEDAS). Intention to treat linear mixed models were used to determine changes in outcomes between the MED-diet and usual care at baseline, 8-weeks and 12-weeks. RESULTS The MED-diet improved CRF (FACIT-F) at 8-weeks [+4.8 (0.0, 9.8); P = 0.05] and 12-weeks [+7.2 (2.2, 12.0); P = 0.005], quality of life (FACIT-G) at 12-weeks [+9.2 (2.7, 15.8); P = 0.006], reduced total body mass at 8-weeks [-2.51 kg (-4.25, -0.78); P = 0.005] and 12-weeks [-2.97 kg (-4.71, -1.25); P = 0.001], lean mass at 8-weeks [-1.50 kg (-2.91, -0.10); P = 0.036], and IL-8 at 8-weeks [-0.18 ng/ml (-0.34, -0.02); P = 0.029] compared to usual care. The MED-diet demonstrated zero adverse events, 91% study completion, 100% attendance, and 81% adherence to the MEDAS. CONCLUSION The MED-diet is safe and feasible, and has the potential to improve CRF and quality of life in overweight men treated with ADT compared to usual care. Further exploration of the MED-diet is warranted in a larger powered sample size to consolidate these findings.
-
3.
Musculoskeletal Responses to Exercise Plus Nutrition in Men with Prostate Cancer on Androgen Deprivation: A 12-Month RCT.
Dalla Via, J, Owen, PJ, Daly, RM, Mundell, NL, Livingston, PM, Rantalainen, T, Foulkes, SJ, Millar, JL, Murphy, DG, Fraser, SF
Medicine and science in sports and exercise. 2021;(10):2054-2065
Abstract
PURPOSE Androgen deprivation therapy (ADT) for prostate cancer has multiple adverse effects on musculoskeletal health. This 12-month randomized controlled trial aimed to assess the effects of multicomponent exercise training combined with whey protein, calcium and vitamin D supplementation on bone mineral density (BMD), structure and strength, body composition, muscle strength, and physical function in ADT-treated men. METHODS Seventy ADT-treated men were randomized to exercise plus supplementation (Ex + Suppl; n = 34) or usual care (control; n = 36). Ex + Suppl involved thrice weekly progressive resistance training plus weight-bearing impact exercise with daily multinutrient supplementation. Primary outcomes were DXA hip and spine areal BMD. Secondary outcomes included the following: tibia and radius pQCT volumetric BMD, bone structure and strength, DXA body composition, pQCT muscle and fat cross-sectional area and muscle density, and muscle strength and physical function. RESULTS Sixty men (86%) completed the study. Mean exercise and supplement adherence were 56% and 77%, respectively. There were no effects of the intervention on bone or body composition outcomes. Ex + Suppl improved leg muscle strength (net difference, (95% confidence interval, or CI), 14.5% (-0.2 to 29.2); P = 0.007) and dynamic mobility (four-square-step test time, -9.3% (-17.3 to -1.3), P = 0.014) relative to controls. Per-protocol analysis of adherent participants (≥66% exercise, ≥80% supplement) showed Ex + Suppl preserved femoral neck aBMD (1.9% (0.1 to 3.8), P = 0.026) and improved total body lean mass (1.0 kg (-0.23 to 2.22), P = 0.044) relative to controls. CONCLUSIONS Exercise training combined with multinutrient supplementation had a limited effect on ameliorating the adverse musculoskeletal consequences of ADT, likely related to the modest intervention adherence.
-
4.
Timing of exercise for muscle strength and physical function in men initiating ADT for prostate cancer.
Newton, RU, Galvão, DA, Spry, N, Joseph, D, Chambers, SK, Gardiner, RA, Hayne, D, Taaffe, DR
Prostate cancer and prostatic diseases. 2020;(3):457-464
-
-
Free full text
-
Abstract
BACKGROUND Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) results in adverse effects, including reduced muscle strength and physical function, potentially compromising daily functioning. We examined whether it was more efficacious to commence exercise at the onset of ADT rather than later in treatment to counter declines in strength and physical function. METHODS One-hundred-and-four men with PCa (68.3 ± 7.0 years) initiating ADT were randomised to immediate exercise (IMX, n = 54) or delayed exercise (DEL, n = 50) for 12 months. IMX comprised 6 months of supervised resistance/aerobic/impact exercise initiated at the onset of ADT with a 6-month follow-up. DEL comprised 6 months of usual care followed by 6 months of resistance/aerobic/impact exercise. Upper and lower body muscle strength and physical function were assessed at baseline, 6 and 12 months. RESULTS There was a significant difference for all strength measures at 6 months favouring IMX (P < 0.001), with net differences in leg press, seated row and chest press strength of 19.9 kg (95% CI, 12.3-27.5 kg), 5.6 kg (3.8-7.4 kg) and 4.3 kg (2.7-5.8 kg), respectively. From 7 to 12 months, DEL increased in all strength measures (P < 0.001), with no differences between groups at 12 months. Similarly, physical function improved (P < 0.001) in IMX compared with DEL at 6 months for the 6-m fast walk (-0.2, 95% CI -0.3 to -0.1 s), 400-m walk (-9.7, -14.8 to -4.6 s), stair climb (-0.4, -0.6 to -0.2 s) and chair rise (-1.0, -1.4 to -0.7 s), with no differences between groups by 12 months, except for the 6-m fast walk (P < 0.001). CONCLUSION Exercise either at the onset or after 6 months of ADT preserves/enhances muscle strength and physical function. However, to avoid initial treatment-related adverse effects on strength and function, exercise therapy should be implemented with initiation of ADT.
-
5.
Metabolomic effects of androgen deprivation therapy treatment for prostate cancer.
Chi, JT, Lin, PH, Tolstikov, V, Oyekunle, T, Chen, EY, Bussberg, V, Greenwood, B, Sarangarajan, R, Narain, NR, Kiebish, MA, et al
Cancer medicine. 2020;(11):3691-3702
Abstract
Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6 months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT-associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the steroid synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3-hydroxybutyric acid and ketogenesis. Third, many acyl-carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourth, ADT was associated with a corresponding reduction in 3-formyl indole (a.k.a. indole-3-carboxaldehyde), a microbiota-derived metabolite from the dietary tryptophan. Indole-3-carboxaldehyde is an agonist for the aryl hydrocarbon receptor and regulates the mucosal reactivity and inflammation. Together, these ADT-associated metabolomic analyses identified reduction in steroid synthesis and ketogenesis as prominent features, suggesting therapeutic potential of restricted ketogenic diets, though this requires formal testing. ADT may also impact the microbial production of indoles related to the immune pathways. Future research is needed to determine the functional impact and underlying mechanisms to prevent ADT-linked comorbidities and diabetes risk.
-
6.
A lifestyle intervention of weight loss via a low-carbohydrate diet plus walking to reduce metabolic disturbances caused by androgen deprivation therapy among prostate cancer patients: carbohydrate and prostate study 1 (CAPS1) randomized controlled trial.
Freedland, SJ, Howard, L, Allen, J, Smith, J, Stout, J, Aronson, W, Inman, BA, Armstrong, AJ, George, D, Westman, E, et al
Prostate cancer and prostatic diseases. 2019;(3):428-437
Abstract
PURPOSE The objective of this study was to test a low-carbohydrate diet (LCD) plus walking to reduce androgen deprivation therapy (ADT)-induced metabolic disturbances. MATERIALS AND METHODS This randomized multi-center trial of prostate cancer (PCa) patients initiating ADT was designed to compare an LCD (≤20g carbohydrate/day) plus walking (≥30 min for ≥5 days/week) intervention vs. control advised to maintain usual diet and exercise patterns. Primary outcome was change in insulin resistance by homeostatic model assessment at 6 months. To detect 20% reduction in insulin resistance, 100 men were required. The study was stopped early after randomizing 42 men due to slow accrual. Secondary outcomes included weight, body composition, lipids, and prostate-specific antigen (PSA). Changes from baseline were compared between arms using rank-sum tests. RESULTS At 6 months, LCD/walking reduced insulin resistance by 4% vs. 36% increase in control (p = 0.13). At 3 months, vs. control, LCD/walking arm significantly lost weight (7.8kg; p<0.001), improved insulin resistance (↑36%; p = 0.015), hemoglobin A1c (↓3.3%; p = 0.01), high-density lipoprotein (HDL) (↑13%; p = 0.004), and triglyceride (↓37%; p = 0.036). At 6 months, weight loss (10.6kg; p<0.001) and HDL (↑27%; p = 0.003) remained significant. LCD/walking preserved total body bone mineral count (p = 0.025), reduced fat mass (p = 0.002), lean mass (p = 0.036), and percent body fat (p = 0.004). There were no differences in PSA. Limitations include the effect of LCD, weight loss vs. walking instruction are indistinguishable, and small sample size. CONCLUSIONS In an underpowered study, LCD/walking did not improve insulin sensitivity at 6 months. Given most secondary outcomes were improved at 3 months with some remaining improved at 6 months and a secondary analysis showed that LCD/walking reduced insulin resistance over the study, supporting future larger studies of LCD/walking intervention to reduce ADT-induced disturbances.
-
7.
Effect of phlebotomy versus oral contraceptives containing cyproterone acetate on the clinical and biochemical parameters in women with polycystic ovary syndrome: a randomized controlled trial.
Behboudi-Gandevani, S, Abtahi, H, Saadat, N, Tohidi, M, Ramezani Tehrani, F
Journal of ovarian research. 2019;(1):78
Abstract
BACKGROUND Reduction of the body iron stores can improve hyperandrogenemia and insulin resistance. This study aimed to compare clinical and para-clinical responses to the treatment of phlebotomy using oral contraceptive pills (OCs) containing cyproterone acetate in women with PCOS. METHODS In this randomized clinical trial, 64 patients with PCOS were randomly assigned to the phlebotomy and OCs groups (n = 32 in each group). The intervention group, using a single treatment procedure, underwent venesection of 450 mL of whole blood at the early follicular phase of the spontaneous or progesterone-induced menstrual cycle. The control group received OCs pills for 3 months from the 1th day of spontaneous or progesterone-induced menstrual cycle onwards for 3 weeks, followed by a pill-free interval of 7 days. The women were evaluated after the 3-month intervention. The primary outcome measure was a change in the HOMA-IR and free androgen index (FAI). Secondary outcomes were changes in the Ferriman-Gallwey (FG) score and other clinical, biochemical and hormonal changes from the baseline (pre-treatment) to week 12. RESULTS In the phlebotomy group, 27 (84.3%) and in the OCs group 30 (93.7%) of the women completed the 3-month follow-up. The median HOMA-IR significantly decreased from 3.5 to 2.7 in the phlebotomy, and from 3.1 to 2.8 in the OCs group, and the changes were comparable between the groups. Median changes in the FAI significantly decreased in both groups, but the differences were not statistically significant between the groups (P = 0.061). With regard to secondary outcomes, mean FG scores in both groups significantly decreased [from 16.8 (6) to 13.3 (7.4), P < 0.028] in the phlebotomy group and [from 14.3 (7) to 9.8 (7.6) in the OCs group, P = 0.001] after 3 months of treatment, but such changes had no statistically significant differences between the groups. During treatment, menstrual cycles became regular in all women in the OCs group and in 12.27 (44.4%) of the women in the phlebotomy group, and the difference was statistically significant (P = 0.001). Despite no statistically significant differences in lipid profiles between the groups at the baseline, triglycerides were significantly higher in the OCs group compared to the phlebotomy at end of follow up (p = 0.019). CONCLUSION Both treatment modalities had similar beneficial effects on insulin resistance and on androgenic profiles. However, OCs was reported more effective in treating menstrual irregularities and phlebotomy had less adverse effects on triglyceride concentrations. TRIAL REGISTRATION Code: IRCT2013080514277N1 .
-
8.
Exercise Mode Specificity for Preserving Spine and Hip Bone Mineral Density in Prostate Cancer Patients.
Newton, RU, Galvão, DA, Spry, N, Joseph, D, Chambers, SK, Gardiner, RA, Wall, BA, Bolam, KA, Taaffe, DR
Medicine and science in sports and exercise. 2019;(4):607-614
Abstract
PURPOSE Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an array of adverse effects, including reduced bone mineral density (BMD) predisposing patients to increased fracture risk. Our purpose was to examine the effects of targeted exercise modes on BMD in men with PCa undergoing ADT. METHODS Between 2009 and 2012, 154 PCa patients 43-90 yr old on ADT were randomized to exercise targeting the musculoskeletal system (impact loading + resistance training [ImpRes], n = 57) supervised for 12 months, cardiovascular and muscular systems (aerobic + resistance training, n = 50) supervised for 6 months followed by a 6-month home-based program, or delayed aerobic exercise (DelAer, n = 47) received exercise information for 6 months followed by 6 months of supervised aerobic exercise (stationary cycling). End points were lumbar spine, hip and whole-body BMD measured by dual-energy x-ray absorptiometry with secondary end points of lean and fat mass, appendicular skeletal muscle mass, and neuromuscular strength. ANOVA was used to compare the exercise groups with DelAer at 6 and 12 months. RESULTS There was a between-group difference in BMD for ImpRes and DelAer at the spine (6 months, P = 0.039; 12 months, P = 0.035) and femoral neck (6 months, P = 0.050), with decline attenuated in ImpRes (~-1.0% vs ~-2.0%). Compared with DelAer, ImpRes increased appendicular skeletal muscle at 6 months (0.3 kg, P = 0.045) and improved muscle strength at 6 and 12 months (P ≤ 0.012) by 9%-34%. A limitation was inclusion of well-functioning patients. CONCLUSION Combined impact loading and resistance exercise attenuates bone loss at the spine and enhances overall musculoskeletal function in PCa patients undergoing ADT.
-
9.
Does exercise impact gut microbiota composition in men receiving androgen deprivation therapy for prostate cancer? A single-blinded, two-armed, randomised controlled trial.
Newton, RU, Christophersen, CT, Fairman, CM, Hart, NH, Taaffe, DR, Broadhurst, D, Devine, A, Chee, R, Tang, CI, Spry, N, et al
BMJ open. 2019;(4):e024872
Abstract
INTRODUCTION A potential link exists between prostate cancer (PCa) disease and treatment and increased inflammatory levels from gut dysbiosis. This study aims to examine if exercise favourably alters gut microbiota in men receiving androgen deprivation therapy (ADT) for PCa. Specifically, this study will explore whether: (1) exercise improves the composition of gut microbiota and increases the abundance of bacteria associated with health promotion and (2) whether gut health correlates with favourable inflammatory status, bowel function, continence and nausea among patients participating in the exercise intervention. METHODS AND ANALYSIS A single-blinded, two-armed, randomised controlled trial will explore the influence of a 3-month exercise programme (3 days/week) for men with high-risk localised PCa receiving ADT. Sixty patients will be randomly assigned to either exercise intervention or usual care. The primary endpoint (gut health and function assessed via feacal samples) and secondary endpoints (self-reported quality of life via standardised questionnaires, blood biomarkers, body composition and physical fitness) will be measured at baseline and following the intervention. A variety of statistical methods will be used to understand the covariance between microbial diversity and metabolomics profile across time and intervention. An intention-to-treat approach will be utilised for the analyses with multiple imputations followed by a secondary sensitivity analysis to ensure data robustness using a complete cases approach. ETHICS AND DISSEMINATION Ethics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (ID: 19827 NEWTON). Findings will be reported in peer-reviewed publications and scientific conferences in addition to working with national support groups to translate findings for the broader community. If exercise is shown to result in favourable changes in gut microbial diversity, composition and metabolic profile, and reduce gastrointestinal complications in PCa patients receiving ADT, this study will form the basis of a future phase III trial. TRIAL REGISTRATION NUMBER ANZCTR12618000280202.
-
10.
Effects of a Group-Mediated Cognitive Behavioral Lifestyle Intervention on Select Social Cognitive Outcomes in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy.
Focht, BC, Lucas, AR, Grainger, E, Simpson, C, Fairman, CM, Thomas-Ahner, JM, Chaplow, ZL, DeScenza, VR, Bowman, J, Clinton, SK
Integrative cancer therapies. 2019;:1534735419893764
Abstract
Objective. To compare the effects of a group-mediated cognitive behavioral (GMCB) exercise and dietary (EX+D) intervention with those of standard-of-care (SC) treatment on select social cognitive outcomes in prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Methods. In the single-blind, 2-arm, randomized controlled Individualized Diet and Exercise Adherence-Pilot (IDEA-P) trial, 32 PCa patients (mean age = 66.2 years; SD = 7.8) undergoing ADT were randomly assigned to a 12-week EX+D intervention (n = 16) or SC treatment (n = 16). The exercise component of the personalized EX+D intervention integrated a combination of supervised resistance and aerobic exercise performed twice per week. The dietary component involved counseling and education to modify dietary intake and composition. Blinded assessments of social cognitive outcomes were obtained at baseline and 2-month and 3-month follow-up. Results. Intent-to-treat analysis of covariance demonstrated that the EX+D intervention resulted in significantly greater improvements in scheduling (P < .05), coping (P < .01), and exercise self-efficacy (P < .05), and satisfaction with function (P < .01) at 3 months relative to SC. Results of partial correlation analysis also demonstrated that select social cognitive outcomes were significantly correlated with primary trial outcomes of mobility performance and exercise participation (P < .05) at 3-month follow-up. Conclusions: The GMCB lifestyle intervention yielded more favorable improvements in relevant social cognitive outcomes relative to SC among PCa patients undergoing ADT. Additionally, more favorable social cognitive outcomes were associated with superior mobility performance and exercise participation following the independent maintenance phase of the EX+D intervention.