Adverse Changes In Body Composition Research Articles

Poor muscle health and cardiometabolic risks associated with antidepressant treatment.

This study aims to investigate whether antidepressant users display differences in fat distribution and muscle composition relative to non-users and to explore risk factors for developing cardiovascular disease (CVD) and type 2 diabetes. The study used quantitative adipose and muscle tissue measures derived from magnetic resonance imaging data from UK Biobank (N = 40,174). Fat distribution and muscle composition of selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) users were compared with sex-, age-, and BMI-matched control individuals. Cox regression models were used to test for increased risk of developing CVD and type 2 diabetes. SSRI users had more visceral fat, smaller muscle volume, and higher muscle fat infiltration compared with matched control individuals. Female users showed a larger increase in BMI over time compared with male users. However, male users displayed an unhealthier body composition profile. Male SSRI users also had an increased risk of developing CVD. Both male and female TCA users showed lower muscle volume and an increased risk of developing type 2 diabetes. Adverse changes in body composition of antidepressant users are not captured by tracking the body weight or the BMI of the patients. These changes may lead to a worsened cardiometabolic risk profile.

Exposure to air pollution, genetic susceptibility, and prevalence of sarcopenia in the UK

BackgroundThe role of environmental factors, particularly air pollutants, in the prevalence of sarcopenia remains unclear. ObjectivesThis study explored the relationship between the prevalence of sarcopenia and prolonged exposure to air pollutants, and investigated potential interactions with genetic susceptibility and inflammation. MethodsData from 408,117 people at baseline and 35,060 participants in the longitudinal analysis in the UK Biobank were used in this prospective cohort study. Utilizing land use regression models, air pollutants (nitrogen dioxide (NO2), nitric oxides (NOx), and particulate matter with aerodynamic diameters of ≤2.5 μm (PM2.5) and ≤10 μm (PM10) were estimated and classified into quartiles. Alterations in body composition were among the secondary results. ResultsLastly, 3353 people (0.8 %) developed sarcopenia. Higher levels of air pollutants were linked to an increased prevalence of sarcopenia after controlling for confounding variables (highest vs lowest quartile: NOx, OR, 1.21 [95 % CI, 1.16–1.26]; NO2, OR, 1.22 [95 % CI, 1.16–1.27]; PM2.5, OR, 1.17 [95 % CI, 1.12–1.22]; PM10, OR, 1.15 [95 % CI, 1.10–1.20]; all P<.001). Longitudinal analysis revealed that air pollutants had adverse changes in body composition, including increased muscle fat infiltration and decreased muscle mass. At baseline, the probability of sarcopenia was strongly correlated with NOx, NO2, PM2.5, and PM10, and increased with elevated PRSBMI or CRP levels in subgroup analyses. ConclusionAir pollutants may contribute to accelerated muscle aging and highlight the importance of environmental factors in sarcopenia development.

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biologic and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential change in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: 1) CT imaging of L3 prior to and after treatment, and 2) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher loss of SMMi after treatment (-11.1% vs. -6.3%, p = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs. -7.1%, p=0.04). In addition, HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs. 77.9, p=0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM were associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.

Changes in Body Composition and Nutritional Periodization during the Training Macrocycle in Football-A Narrative Review.

Nutrition periodization in football training is an important determinant of adaptation to cyclic training loads. Personalizing an athlete's diet is crucial to ensure optimal performance and body composition, depending on the phase of training. The purpose of this review is to answer the question of how the body composition of football players changes over the training macrocycle and how dietary recommendations should be tailored to specific training periods. The review of scientific evidence was conducted based on the available literature, typing in phrases related to training and nutrition periodization using the PubMed and Google Scholar database methodology tools. A literature search resulted in the selection of 346 sources directly related to the topic of the study, and then those with the highest scientific value were selected. There is a need to adjust energy and nutrient intake according to the different training phases in a football player's preparation cycle. During the preparatory phase, it is recommended to increase protein and energy intake to support anabolic processes and muscle mass development. During the competitive period, due to the intensity of matches and training, the importance of carbohydrates for glycogen replenishment and recovery is emphasized. The transition phase requires the regulation of caloric intake to prevent adverse changes in body composition. Hydration has been identified as a key element in each phase of training. Cooperation between coaches, nutritionists, and players is essential to optimize sports performance and rapid recovery, and the authors recommend continuous adaptation and nutritional optimization as an integral part of football training.

The consequences of growth hormone deficiency in adults

Adult growth hormone deficiency (GHD) is a result of the decreased growth hormone (GH) production and secretion from the anterior pituitary gland in adulthood, that cannot be explained by the physiological ageing process. GHD is associated with numerous deleterious consequences such as adverse changes in body composition, carbohydrate and lipid metabolism, alterations in the cardiovascular system, and deterioration in the quality of life (QoL). Most of these complications are at least partially reversible during recombinant human growth hormone (rhGH) replacement therapy. Thus, physicians and particularly endocrinologists, should consider GHD diagnosis and select patients who could benefit from rhGH therapy.

COCs with estradiol valerate/dienogest vs 17β-estradiol/nomegestrol acetate: effects on metabolism and body composition in menopausal transition women

Context: Women during the menopausal transition (MT) have reduced fertility, and yet frequency of pregnancy in the absence of contraception is about 30%. Late reproductive age women are at a higher risk of adverse pregnancy outcome, and thus require effective contraceptive methods if pregnancy is to be avoided. The use of combined oral contraceptives (COCs), in addition to highly effective pregnancy prevention, is associated with important non-contraceptive benefits for perimenopausal women, such as an improved bleeding pattern, particularly in the setting of irregular or heavy menses, alleviation of vasomotor symptoms. The main requirements in choosing СOCs for women during the MT are their safety, metabolic neutrality, and no weight gain, because during the MT occurs adverse changes in metabolic profile and body composition.

PD21-08 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023PD21-08 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER Nicholas Deebel, Jessica Delgado, Jesse Ory, Justin Loloi, Ari Bernstein, Sirpi Nackeeran, and Ranjith Ramasamy Nicholas DeebelNicholas Deebel More articles by this author , Jessica DelgadoJessica Delgado More articles by this author , Jesse OryJesse Ory More articles by this author , Justin LoloiJustin Loloi More articles by this author , Ari BernsteinAri Bernstein More articles by this author , Sirpi NackeeranSirpi Nackeeran More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen deprivation therapy (ADT) is frequently used in the treatment of localized PCa. Many men receiving temporary ADT for localized prostate cancer fail to achieve baseline testosterone (T) levels after cessation. However, current literature limits the ability to predict prolonged testosterone deficiency (TD) based on ADT regimen and duration. Testosterone recovery in men with localized prostate cancer receiving temporary ADT was assessed. METHODS: A globally federated health research network (TriNetX) was used to identify men diagnosed with prostate cancer undergoing temporary ADT. Inclusion criteria consisted of: a clinically localized prostate cancer and eugonadal mean baseline T level (>300 ng/dL). Prior to starting ADT two cohorts were identified: Men receiving LHRH antagonists or LHRH agonists and men receiving combined ADT (LHRH agonist and antiandrogens). Further stratification was based on treatment duration of 6 months (short-term) or 18 months (long-term) to compare T recovery profiles 5 years after ADT cessation. RESULTS: A total of 28,583 men received LHRH agonist or antagonist therapy alone and 20,188 men received combination ADT. A total of 46.7% of men who received short-term LHRH agonists or antagonists and 40.6% of men who received short-term combined ADT recovered to mean baseline T levels at 5 years (p = 0.06). Only men who received short-term LHRH agonist/antagonists recovered to a mean eugonadal level at 5 year follow-up. Meanwhile, 50% of men who received long-term LHRH agonist/antagonist therapy and 10.7% of men who received long-term combined ADT recovered to mean baseline T levels at 5 years (p < 0.0001). However, neither group recovered to a mean eugonadal T level. CONCLUSIONS: Most patients failed to recover to mean baseline and eugonadal T levels at 5-year follow-up. Given that TD is associated with a myriad of adverse effects such as metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and hypogonadal symptoms, serum T levels must be closely followed in men receiving ADT following treatment cessation. Source of Funding: NIH Grant R01 DK130991 and Clinician Scientist Development Grant from the ACS to RR © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e593 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Deebel More articles by this author Jessica Delgado More articles by this author Jesse Ory More articles by this author Justin Loloi More articles by this author Ari Bernstein More articles by this author Sirpi Nackeeran More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

New Horizons: Testosterone or Exercise for Cardiometabolic Health in Older Men.

Middle-aged and older men have typically accumulated comorbidities, are increasingly sedentary, and have lower testosterone concentrations (T) compared to younger men. Reduced physical activity (PA) and lower T both are associated with, and may predispose to, metabolically adverse changes in body composition, which contribute to higher risks of cardiometabolic disease. Exercise improves cardiometabolic health, but sustained participation is problematic. By contrast, rates of T prescription have increased, particularly in middle-aged and older men without organic diseases of the hypothalamus, pituitary, or testes, reflecting the unproven concept of a restorative hormone that preserves health. Two recent large randomized trials of T, and meta-analyses of randomized trials, did not show a signal for adverse cardiovascular (CV) events, and T treatment on a background of lifestyle intervention reduced type 2 diabetes by 40% in men at high risk. Men with both higher endogenous T and higher PA levels have lower CV risk, but causality remains unproven. Exercise training interventions improve blood pressure and endothelial function in middle-aged and older men, without comparable benefits or additive effects of T treatment. Therefore, exercise training improves cardiometabolic health in middle-aged and older men when effectively applied as a supervised regimen incorporating aerobic and resistance modalities. Treatment with T may have indirect cardiometabolic benefits, mediated via favorable changes in body composition. Further evaluation of T as a pharmacological intervention to improve cardiometabolic health in aging men could consider longer treatment durations and combination with targeted exercise programs.

A phase II trial modifying metabolic syndrome and cardiovascular risk for patients with prostate cancer on ADT using a risk factor modification program and continuous Fitbit monitoring (ProTrio).

TPS273 Background: Prostate cancer is a disease of older age, and there is significant overlap with age-related illnesses. Androgens play a critical role in prostate cancer but also have been linked to cardiovascular (CV) disease, metabolic syndrome, bone health, and frailty. ADT is associated with an increased risk of CV events primarily due to increased rates of diabetes, dyslipidemia, and adverse changes in body composition. We assume that prostate cancer and age-related illnesses share biology with therapeutic implications in a subset of men. The ProTrio trial will test the hypothesis that a 16-week digital risk factor modification program will improve 10-year atherosclerotic cardiovascular disease (ASCVD) risk score as compared to usual care in men with potentially lethal prostate cancer receiving ADT. Methods: This single center, open-label, randomized phase II trial is evaluating a 16-week digital risk factor modification program, which includes an exercise prescription (150 minutes of titrated cardiovascular exercise and resistance exercise 2 times a week) with support via a smart phone application (Moving Analytics) and Fitbit, in patients with prostate cancer who are receiving ADT compared to usual care with Fitbit monitoring. Eligible patients are men receiving ADT +/- an androgen signaling inhibitor for at least 3 months prior to enrollment. The study will enroll to two cohorts: (1) distant metastatic disease and (2) biochemically recurrent or regional lymph node disease. Patients will be stratified according to their baseline ASCVD risk score. The primary endpoint is the difference in ASCVD risk score post-intervention. Secondary endpoints include difference in metabolic severity index z-score, PSA velocity, 6-minute walk, 5X Sit-to-Stand, body composition, physical activity measured by Fitbit, and health-related quality of life. Up to 100 patients will be enrolled in each cohort. A clinically relevant improvement in ASCVD score reduction is 2.5%. With 44 men per arm, after 12% dropout, we can detect an improvement of 2.5% vs. 0% at a 2-sided 5% significance level with 80% power assuming a standard deviation (SD) of 4.125%. A sample size adjustment is planned based on the SD of the first cohort to reach 44 patients. Each cohort will undergo futility analysis once half the men are enrolled. The study is enrolling at MD Anderson Cancer Center. Clinical trial information: NCT05054296 .

A Systematic Review of Testosterone Therapy in Men With Spinal Cord Injury or Traumatic Brain Injury.

Spinal cord injuries (SCI) and traumatic brain injuries (TBI) increase the risk of testosterone deficiency and result in adverse changes in body composition and poor functional outcomes. The current systematic review aims to provide insights into the use of testosterone therapy for treating men with SCI and TBI. The PubMed and EMBASE databases were systematically reviewed using appropriate terms, and resulting manuscripts were screened using defined Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The patient population included male patients with SCI or TBI. Further inclusion criteria were: a) human participants 18 years of age or older; b) manuscript published in English; c) study included an intervention with exogenous testosterone; and d) articles published in peer-reviewed journals with full text available. Two reviewers independently extracted data regarding injury type, intervention, and outcomes. Following screening for inclusion/exclusion criteria, a total of 12 primary research studies conducted over the last 30 years were included. Men with SCI were investigated in 11 articles. The combination of testosterone patches and resistance training with functional electrical stimulation (FES) for 16 weeks in men with SCI and an average baseline testosterone level above the cutoff for testosterone deficiency increased muscle mass, strength, bone quality, and basal metabolic ratewhile testosterone patches without exercise for 16 weeks produced no significant changes in these parameters. Testosterone patches for 12 months in men with SCI and testosterone deficiency also increased lean tissue mass (LTM) and resting energy expenditure (REE). In one study, men with TBI and testosterone deficiency receiving testosterone gel for eight weeks showed a non-statistically significant greater absolute change in functional independence measure (FIM) and grip strength compared to a placebo group. Testosterone therapy with exercise may help improve muscle mass, bone health, strength, energy expenditure, and cardiac health in men with SCI without major side effects. It is difficult to draw conclusions regarding the effects of testosterone therapy in men with TBI based on the limited available evidence. Further investigation is warranted to explore the relationship between testosterone therapy and recovery after SCI and TBI.

Onset of androgen deprivation therapy leads to rapid deterioration of body composition, physical performance, cardiometabolic health and quality-of-life in prostate cancer patients

Objectives To assess the adverse impact of the first 5 months of androgen deprivation therapy on body composition, physical performance, cardiometabolic health and health-related quality-of-life in prostate cancer patients. Materials and Methods Thirty-four prostate cancer patients (70 ± 7 years) were assessed shortly after initiation of androgen deprivation therapy and again 5 months thereafter. Measurements consisted of whole-body dual-energy x-ray absorptiometry (body composition), computed tomography scanning of the upper leg (muscle mass), one-repetition maximum leg press (muscle strength), cardiopulmonary exercise testing (aerobic capacity), blood draws (metabolic parameters), accelerometry (habitual physical activity) and questionnaires (health-related quality-of-life). Data were analyzed with Student’s paired t-tests. Results Over time, whole-body fat mass (from 26.2 ± 7.7 to 28.4 ± 8.3 kg, p < 0.001) and fasting insulin (from 9.5 ± 5.8 to 11.3 ± 6.9 mU/L, p < 0.001) increased. Declines were observed for quadriceps cross-sectional area (from 66.3 ± 9.1 to 65.0 ± 8.5 cm2, p < 0.01), one-repetition maximum leg press (from 107 ± 27 to 100 ± 27 kg, p < 0.01), peak oxygen uptake (from 23.2 ± 3.7 to 20.3 ± 3.4 mL/min/kg body weight, p < 0.001), step count (from 7,048 ± 2,277 to 5,842 ± 1,749 steps/day, p < 0.01) and health-related quality-of-life (from 84.6 ± 13.5 to 77.0 ± 14.6, p < 0.001). Conclusions Androgen deprivation therapy induces adverse changes in body composition, muscle strength, cardiometabolic health and health-related quality-of-life already within 5 months after the start of treatment, possibly largely contributed by diminished habitual physical activity. Prostate cancer patients should, therefore, be stimulated to increase their habitual physical activity immediately after initiation of androgen deprivation therapy, to limit adverse side-effects and to improve health-related quality-of-life.

Persistent Testosterone Suppression After Cessation of Androgen Deprivation Therapy for Prostate Cancer.

Introduction Many men receiving temporary androgen deprivation therapy (ADT) for localized prostate cancer fail to achieve baseline testosterone levels after cessation. Testosterone recovery in men with localized prostate cancer receiving temporary ADT was assessed. Methods A global federated health research network (TriNetX) was used to identify men diagnosed with prostate cancer undergoing temporary ADT. Two cohorts were identified: men receiving luteinizing hormone-releasing hormone (LHRH) antagonists or LHRH agonists, and men receiving combined ADT (LHRH agonist and antiandrogens). Further stratification was based on a treatment duration of six months (short-term) or 18 months (long-term) to compare testosterone (T) recovery profiles five years after ADT cessation. Results A total of 28,583 men received LHRH agonist or antagonist therapy alone, and 20,188 men received combination ADT. A total of 46.7% of men who received short-term LHRH agonists or antagonistsand 40.6% of men who received short-term combined ADT, recovered to mean baseline T levels at five years. Only men who received short-term LHRH agonists/antagonists recovered to eugonadal levels at the five-year follow-up. Around 50% of men who received long-term LHRH agonist/antagonist therapy and 10.7% of men who received combined ADT, recovered to mean baseline T levels at five years. However, neither group recovered to eugonadal T levels. Conclusions At the five-year follow-up after ADT cessation, most patients failed to recover to their mean baseline and eugonadal T levels. Given that testosterone deficiency is associated with metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and hypogonadal symptoms, serum T levels must be closely monitored in men receiving ADT following treatment cessation.

Associations among body composition parameters and quality of life in peritoneal dialysis patients

Health-related quality of life (HRQOL) is an important issue among patients undergoing dialysis treatment. Peritoneal dialysis (PD) is associated with a number of adverse body composition changes. However, whether body composition is associated with HRQOL is uncertain. The purpose of this study was to analyze the effects of body composition on HRQOL in PD patients. We performed a cross-sectional observational study on the association between body composition and HRQOL in PD patients at a single center. Body composition was determined by multifrequency bioimpedance spectroscopy. HRQOL is summarized to three composite scores: kidney disease component summary (KDCS), physical component summary (PCS), and mental component summary (MCS). The relationships between HRQOL and the hydration index, lean tissue index (LTI), and fat tissue index (FTI) were analyzed by regression analysis. One hundred and ninety-seven PD patients were included in the present study. Patients with severe fluid overload showed a lower PCS. The hydration index and FTI showed statistically significant negative associations with PCS. In subgroup analysis, the associations between the hydration index and PCS remained robust after stratifying according to sex, age, and residual urine. Our results indicated that both the hydration index and FTI were negatively associated with HRQOL, especially PCS.

Effects of aromatase inhibitor therapy on visceral adipose tissue area and cardiometabolic health in postmenopausal women with early and locally advanced breast cancer.

Aromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen receptor-positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In nonbreast cancer populations, experimentally induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk. Given that AI treatment blocks oestradiol production, we hypothesized that AI treatment would increase VAT. We conducted a prospective 12-month cohort study of 52 postmenopausal women newly initiating AI treatment (median age: 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age: 63.5 years). VAT area and other body composition parameters were measured at baseline, 6months and 12 months using dual X-ray absorptiometry. Other risk markers of cardiometabolic health were also assessed. In women initiating AI treatment, there was no statistically significant difference in VAT area after 12 months when compared to controls, with a mean adjusted difference of -5.00 cm2 (-16.9, 6.91), p = .55. Moreover, changes in total fat mass, lean mass, subcutaneous adipose tissue area, hepatic steatosis and measures in endothelial function were also not statistically different between groups after 12 months. Findings were similar after adjustments for activity levels and coronavirus disease 2019 lockdown duration. These data provide reassurance that over the initial 12 months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study.

PSUN311 JTV-519 Alleviates the Impairment of FGF21 Axis Signaling after Spinal Cord Contusion in Mice

Abstract Spinal cord injury (SCI) causes adverse changes in body composition and metabolic profile due to dramatic loss of skeletal muscle mass and an extremely sedentary lifestyle. These abrupt and permanent changes increase the risk for cardiovascular disease, liver disorders, and type 2 diabetes compared to the general population. We have reported that metabolic dysregulation following SCI due to transection is associated with impaired fibroblast growth factor 21 (FGF21) and adiponectin (ADPN) signaling [1], two important regulators of metabolism [2, 3]. JTV519, which stabilizes ryanodine receptors and blocks calcium uptake via SERCA [4], has been reported to have a strong cardioprotective effect via stabilization of ryanodine receptor 2. We examined the effects of SCI caused by contusion (a more common cause of SCI), with or without JTV519 administration, on FGF21 and ADPN signaling in tissues collected from mice at 56 days after SCI. SCI reduced serum and hepatic mRNA levels of FGF21 by 75% and 45%, respectively, compared to sham mice. SCI also significantly diminished FGF21 receptor (FGF-R1) and coreceptor (beta-klotho, KLB) mRNA expression in adipose tissue. In addition, SCI decreased serum ADPN levels, particularly its high molecular weight (HMW) isoform which is the most potent form of the protein. These inhibitory effects were associated with decreased hepatic mRNA expression for PPARalpha (55%), type-2 adiponectin receptor (AdipoR2; 70%), and Glut4 (75%). In addition, SCI reduced mRNA expression of leptin (by 85%) and UCP1 (by 95%) in adipose tissue. In skeletal muscle (gastrocnemius), SCI lowered mRNA expression of PGC1alpha (by 38%), ADPN (by 80%), FGF-R1 (by 35%) and AdipoR1 (by 20%) compared to sham mice. Treating sham-mice with JTV519 upregulated FGF21 and ADPN serum and mRNA levels as well as the expression of the associated metabolic genes of interest (mentioned above). Likewise, SCI-mice treated with JTV519 also demonstrated upregulation of serum levels of FGF21, the HMW isoform of ADPN, and hepatic FGF21 mRNA expression compared to vehicle-treated SCI-mice. Decreased hepatic mRNA expression of PPARalpha, AdipoR2, Glut4 and FGF-R1 and KLB mRNA in adipose tissue were also reversed after JTV519 administration, with levels approximately equivalent to those observed in sham-vehicle treated mice but lower than sham-JTV519 treated mice. Moreover, JTV519 treatment protected against SCI-induced decreases of PGC1alpha, ADPN and FGF-R1 mRNA expression in the gastrocnemius. These data imply that JTV-519 is able to alleviate SCI-induced impairments of FGF21/ADPN signaling. Therefore, JTV519 could be a potential pharmacological agent to treat metabolic dysfunction after SCI.

Sarcopenia in patients with diabetes mellitus.

Diseases such as diabetes mellitus may be associated with adverse changes in body composition. Sarcopenia is characterized by a progressive and generalized loss of skeletal muscle mass and functionality. To investigate the relationship between type 2 diabetes mellitus (T2DM) and sarcopenia. In a retrospective, non-randomized study, 35 T2DM patients, aged 20-80 years, were assessed for sarcopenia prevalence compared to controls (n=16). Appendicular skeletal mass (ASM) (kg) was measured, and sarcopenia was defined as SMI <7.0 and <5.7 kg/m2, in males and females, respectively, using the European Working Group on Sarcopenia in Elderly (EWGOSP) definition. Low physical performance was defined as a walking speed of <0.8 m/s. Incidence of sarcopenia was significantly higher in T2DM patients vs. controls (27% vs. 20%, p=0.01) and elderly vs. young participants (40% vs. 12%, p<0.001), respectively. Walking velocity was significantly lower in T2DM patients compared to male and female controls (1.08±0.22 vs. 1.23±0.18 and 1.07±0.26 vs. 1.26±0.16, respectively, p<0.001,). A moderate prevalence of sarcopenia in patients with type 2 diabetes mellitus was observed, which appeared to increase significantly in older men. Finally, incidence of T2DM displayed decreased physical performance in both genders.

Adverse Changes in Body Composition During the Menopausal Transition and Relation to Cardiovascular Risk: A Contemporary Review.

The menopausal transition period in aging women is strongly associated with weight gain. Evidence shows that weight changes during menopause increases the risk of developing cardiovascular disease (CVD) in postmenopausal women. However, the potential mechanisms that cause weight gain and adverse changes to body composition specifically during the menopausal transition period remain to be elucidated. In this contemporary review, we examined recent evidence for adverse changes in body composition at midlife during the menopausal transition and the link to increased CVD risk and described factors that may contribute to these changes, including normal chronological aging, hormonal factors (decreased estrogen, etc.), behavioral factors (changes in diet, physical activity), or other emerging factors (e.g., sleep). This review focused on identifying factors that make the menopausal transition period a critical window for prevention of CVD. Future study is needed to decipher the extent to which hormonal changes, age-related factors, and behavioral factors interact with and contribute to increased CVD risk in women undergoing menopause. Understanding the causes of weight gain during the menopausal transition may help to inform strategies to mitigate adverse CVD outcomes for women transitioning through menopause.

MP48-02 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP48-02 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER Jessica Delgado, Jesse Ory, Joshua Bitran, Ruben Blachman Braun, Sirpi Nackeeran, and Ranjith Ramasamy Jessica DelgadoJessica Delgado More articles by this author , Jesse OryJesse Ory More articles by this author , Joshua BitranJoshua Bitran More articles by this author , Ruben Blachman BraunRuben Blachman Braun More articles by this author , Sirpi NackeeranSirpi Nackeeran More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002619.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Introduction: ADT plays a fundamental role in the treatment of localized prostate cancer. However, there is limited data regarding testosterone recovery in men who have received ADT for localized prostate cancer. Identification of T recovery profiles associated with ADT will facilitate personalization of ADT regimens and guide future treatment strategies to minimize the risk of T deficiency in patients following treatment for prostate cancer. Objective: Temporary use of Androgen Deprivation Therapy (ADT) is a cornerstone in the treatment of localized prostate cancer. However, the ability for testosterone to recover after ADT is not well understood. The aim of this study was to investigate testosterone recovery in men with localized prostate cancer following ADT. METHODS: A global federated health research network (TriNetX) was used to identify men with a diagnosis of prostate cancer who underwent temporary use of ADT. Three cohorts were identified: Men who received LHRH antagonists, LHRH agonists, and men who received combined ADT (LHRH agonist and antiandrogens). Further stratification was based on treatment duration of 6 or 18 months to compare T recovery profiles 5 years after ADT cessation. RESULTS: A total of 17,884 men received LHRH agonists alone, 12,767 men received combined ADT, and 628 men received LHRH antagonist therapy alone. Eugondal mean baseline T level (>300 ng/dL) prior to starting ADT was an inclusion criterion for all men. Five years after ADT cessation, 36% of patients who received LHRH agonists recovered eugondal T levels, 26% recovered after LHRH antagonist therapy, and 36.8% recovered after combined ADT. Overall, more than half of men who received ADT failed to recover eugondal T levels even 5 years after treatment cessation. CONCLUSIONS: Five years after ADT cessation for localized prostate cancer, incomplete testosterone recovery persists in >50% of the men. Since, testosterone deficiency will lead to metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and poor quality of life, serum T levels need to be closely followed in men receiving ADT. Source of Funding: Funding to access the TriNetX database was provided in part by an educational grant from Acerus Pharmaceuticals. Acerus Pharmaceuticals was not involved in the planning, design, writing or any other aspect of this project. © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e820 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jessica Delgado More articles by this author Jesse Ory More articles by this author Joshua Bitran More articles by this author Ruben Blachman Braun More articles by this author Sirpi Nackeeran More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF DownloadLoading ...

Persistent Testosterone Suppression After Cessation of Androgen Deprivation Therapy for Localized Prostate Cancer

ABSTRACT Introduction ADT plays a fundamental role in the treatment of localized prostate cancer. However, there is limited data regarding testosterone recovery in men who have received ADT for prostate cancer. Identification of T recovery profiles associated with ADTs will facilitate personalization of ADT regimens and guide future treatment strategies to minimize the risk of T deficiency in patients with prostate cancer. Objective Temporary use of Androgen Deprivation Therapy (ADT) is a cornerstone in the treatment of localized prostate cancer. However, the ability for testosterone to recover after ADT is not well understood. The aim of this study was to investigate testosterone recovery in men with prostate cancer following varying ADT modalities and treatment durations. Methods A global federated health research network (TriNetX) was used to identify men with a diagnosis of prostate cancer who underwent temporary use of ADT. Three cohorts were identified: Men who received LHRH antagonists, LHRH agonists, and men who received combined ADT (LHRH agonist and antiandrogens). Further stratification was based on treatment duration of 6 or 18 months to compare T recovery profiles at follow up periods of 2 and 5 years. Results A total of 17,884 men received LHRH agonists alone, 12,767 men received combined ADT, and 628 men received LHRH antagonist therapy alone. Eugondal mean baseline T level (&amp;gt;300 ng/dL) prior to starting ADT was an inclusion criterion for all men. Five years after ADT cessation, 36% of patients who received LHRH agonists recovered eugondal T levels, 26% recovered after LHRH antagonist therapy, and 36.8% recovered after combined ADT. Overall, more than half of men who received ADT failed to recover eugondal T levels even 5 years after treatment cessation. Conclusions Five years after ADT cessation, incomplete testosterone recovery persists in more than 50% of men. Testosterone deficiency will lead to metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and poor quality of life and needs to be evaluated even after cessation of ADT. Disclosure No

Stimulated Insulin Secretion Predicts Changes in Body Composition Following Weight Loss in Adults with High BMI

BackgroundThe aim of obesity treatment is to promote loss of fat relative to lean mass. However, body composition changes with calorie restriction differ among individuals. ObjectivesThe goal of this study was to test the hypothesis that insulin secretion predicts body composition changes among young and middle-age adults with high BMI (in kg/m2) following major weight loss. MethodsExploratory analyses were conducted with pre-randomization data from 2 large feeding trials: the Framingham, Boston, Bloomington, Birmingham, and Baylor study (FB4; n = 82, 43.9% women, BMI ≥27) and the Framingham State Food Study [(FS)2; n = 161, 69.6% women, BMI ≥25]. Participants in the 2 trials consumed calorie-restricted moderate-carbohydrate or very-low-carbohydrate diets to produce 12–18% weight loss in ∼14 wk or 10–14% in ∼10 wk, respectively. We determined insulin concentration 30 min after a 75-g oral glucose load (insulin-30) as a measure of insulin secretion and HOMA-IR as a measure of insulin resistance at baseline. Body composition was determined by DXA at baseline and post–weight loss. Associations were analyzed using general linear models with adjustment for covariates. ResultsIn FB4, higher insulin-30 was associated with a smaller decrease in fat mass (0.441 kg per 100 μIU/mL increment in baseline insulin-30; P = 0.005; –1.20-kg mean difference between the first compared with the fifth group of insulin-30) and a larger decrease in lean mass (–0.465 kg per 100 μIU/mL; P = 0.004; 1.27-kg difference). Participants with higher insulin-30 lost a smaller proportion of weight loss as fat (–3.37% per 100 μIU/mL; P = 0.003; 9.20% difference). Greater HOMA-IR was also significantly associated with adverse body composition changes. Results from (FS)2 were qualitatively similar but of a smaller magnitude. ConclusionsBaseline insulin dynamics predict substantial individual differences in body composition following weight loss. These findings may inform understanding of the pathophysiological basis for weight regain and the design of more effective obesity treatment. Registered at http://www.clinicaltrials.gov clinicaltrials.gov as NCT03394664 and NCT02068885.