1.
Metabolic changes in patients with prostate cancer during androgen deprivation therapy.
Mitsuzuka, K, Arai, Y
International journal of urology : official journal of the Japanese Urological Association. 2018;(1):45-53
Abstract
Androgen deprivation therapy continues to be widely used for the treatment of prostate cancer despite the appearance of new-generation androgen-receptor targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms in patients with metastatic prostate cancer and might have a survival benefit in some patients, but it causes undesirable changes in lipid, glucose, muscle or bone metabolism. These metabolic changes could lead to new onset or worsening of diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, sarcopenia or fracture. Several studies examining the influence of androgen deprivation therapy in Japanese patients with prostate cancer also showed that metabolic changes, such as weight gain, dyslipidemia or fat accumulation, can occur as in patients in Western countries. Efforts to decrease these unfavorable changes and events are important. First, overuse of androgen deprivation therapy for localized or elderly prostate cancer patients should be reconsidered. Second, intermittent androgen deprivation therapy might be beneficial for selected patients who suffer from impaired quality of life as a result of continuous androgen deprivation therapy. Third, education and instruction, such as diet or exercise, to decrease metabolic changes before initiating androgen deprivation therapy is important, because metabolic changes are likely to occur in the early androgen deprivation therapy period. Fourth, routine monitoring of weight, laboratory data or bone mineral density during androgen deprivation therapy are required to avoid unfavorable events.
2.
Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.
Dawson, JK, Dorff, TB, Todd Schroeder, E, Lane, CJ, Gross, ME, Dieli-Conwright, CM
BMC cancer. 2018;(1):368
Abstract
BACKGROUND Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. METHODS Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE = TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE = PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g⋅day- 1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m2), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. RESULTS A total of 37 participants were randomized; 32 participated in the intervention (EXE n = 13; NoEXE n = 19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d = 0.9), sarcopenia prevalence (d = 0.8), body fat % (d = 1.1), strength (d = 0.8-3.0), and prostate cancer-specific quality of life (d = 0.9) compared to NoEXE (p < 0.05). No significant differences were observed between groups for physical function or MetS-related variables except waist circumference (d = 0.8). CONCLUSIONS A 12-week resistance training intervention effectively improved sarcopenia, body fat %, strength and quality of life in hypogonadal prostate cancer patients, but did not change MetS or physical function. PRO did not offer additional benefit in improving body composition. TRIAL REGISTRATION ClinicalTrials.gov: NCT01909440 . Registered 24 July 2013.
3.
Medical therapy for Cushing's disease: adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers.
Fleseriu, M, Petersenn, S
Pituitary. 2015;(2):245-52
Abstract
Morbidity and mortality in Cushing's disease (CD) patients are increased if patients are not appropriately treated. Surgery remains the first line therapy, however the role of medical therapy has become more prominent in patients when biochemical remission is not achieved/or recurs after surgery, while waiting effects of radiation therapy or when surgery is contraindicated. Furthermore, use of preoperative medical therapy has been also recognized. In addition to centrally acting therapies (reviewed elsewhere in this special issue), adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are frequently used. A PubMed search of all original articles or abstracts detailing medical therapy in CD, published within 12 months (2013-2014), were identified and pertinent data extracted. Although not prospectively studied, ketoconazole and metyrapone have been the most frequently used medical therapies. A large retrospective ketoconazole study showed that almost half of patients who continued on ketoconazole therapy achieved biochemical control and clinical improvement; however almost 20% discontinued ketoconazole due to poor tolerability. Notably, hepatotoxicity was usually mild and resolved after drug withdrawal. Etomidate remains the only drug available for intravenous use. A new potent inhibitor of both aldosterone synthase and 11β-hydroxylase, following the completion of a phase II study LCI699 is being studied in a large phase III with promising results. Mifepristone, a glucocorticoid receptor antagonist, has been approved for hyperglycemia associated with Cushing's syndrome based on the results of a prospective study where it produced in the majority of patients' significant clinical and metabolic improvement. Absence of both a biochemical marker for remission and/or diagnosis of adrenal insufficiency remain, however, a limiting factor. Patient characteristics and preference should guide the choice between different medications in the absence of clinical trials comparing any of these therapies. Despite significant progress, there is still a need for a medical therapy that is more effective and with less adverse effects for patients with CD.