A randomized controlled trial on the effectiveness of strength training on clinical and muscle cellular outcomes in patients with prostate cancer during androgen deprivation therapy: rationale and design

Background Studies indicate that strength training has beneficial effects on clinical health outcomes in prostate cancer patients during androgen deprivation therapy. However, randomized controlled trials are needed to scientifically determine the effectiveness of strength training on the muscle cell level. Furthermore, close examination of the feasibility of a high-load strength training program is warranted. The Physical Exercise and Prostate Cancer (PEPC) trial is designed to determine the effectiveness of strength training on clinical and muscle cellular outcomes in non-metastatic prostate cancer patients after high-dose radiotherapy and during ongoing androgen deprivation therapy. Methods/design Patients receiving androgen deprivation therapy for 9-36 months combined with external high-dose radiotherapy for locally advanced prostate cancer are randomized to an exercise intervention group that receives a 16 week high-load strength training program or a control group that is encouraged to maintain their habitual activity level. In both arms, androgen deprivation therapy is continued until the end of the intervention period. Clinical outcomes are body composition (lean body mass, bone mineral density and fat mass) measured by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning (muscle strength and cardio-respiratory fitness) assessed with physical tests and psycho-social functioning (mental health, fatigue and health-related quality of life) assessed by questionnaires. Muscle cellular outcomes are a) muscle fiber size b) regulators of muscle fiber size (number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors and proteins involved in muscle protein degradation and muscle hypertrophy) and c) regulators of muscle fiber function such as proteins involved in cellular stress and mitochondrial function. Muscle cellular outcomes are measured on muscle cross sections and muscle homogenate from muscle biopsies obtained from muscle vastus lateralis. Discussion The findings from the PEPC trial will provide new knowledge on the effects of high-load strength training on clinical and muscle cellular outcomes in prostate cancer patients during androgen deprivation therapy. Trial registration ClinicalTrials.gov: NCT0065822

Effects of training, detraining, and retraining on strength, hypertrophy, and myonuclear number in human skeletal muscle

Previously trained mouse muscles acquire strength and volume faster than naïve muscles; it has been suggested that this is related to increased myonuclear density. The present study aimed to determine whether a previously strength-trained leg (mem-leg) would respond better to a period of strength training than a previously untrained leg (con-leg). Nine men and 10 women performed unilateral strength training (T1) for 10 wk, followed by 20 wk of detraining (DT) and a 5-wk bilateral retraining period (T2). Muscle biopsies were taken before and after each training period and analyzed for myonuclear number, fiber volume, and cross-sectional area (CSA). Ultrasound and one repetition of maximum leg extension were performed to determine muscle thickness (MT) and strength. CSA (~17%), MT (~10%), and strength (~20%) increased during T1 in the mem-leg. However, the myonuclear number and fiber volume did not change. MT and CSA returned to baseline values during DT, but strength remained elevated (~60%), supporting previous findings of a long-lasting motor learning effect. MT and strength increased similarly in the mem-leg and con-leg during T2, whereas CSA, fiber volume, and myonuclear number remained unaffected. In conclusion, training response during T2 did not differ between the mem-leg and con-leg. However, this does not discount the existence of human muscle memory, since no increase in the number of myonuclei was detected during T1 and no clear detraining effect was observed for cell size during DT; thus, the present data did not allow for a rigorous test of the muscle memory hypothesis. NEW & NOTEWORTHY If a long-lasting intramuscular memory exists in humans, this will affect strength-training advice for both athletes and the public. Based on animal experiments, we hypothesized that such a memory exists and that it is related to the myonuclear number. However, a period of unilateral strength training, followed by detraining, did not increase the myonuclear number. The training response, during a subsequent bilateral retraining period, was not enhanced in the previously trained leg.