1.Metabolic complications of androgen deprivation therapy and its intervention management.
Yong-Hui HU ; Song WU ; Meng ZHANG
National Journal of Andrology 2018;24(3):277-281
Androgen deprivation therapy (ADT) is one of the dominant treatment options for advanced prostate cancer, which has been certified to significantly improve the overall survival of prostate cancer patients. However, it sometimes can also produce severe adverse effects on body metabolism. This review summarizes the adverse effects of ADT on body composition, the levels of cholesterol and blood glucose, and the cardiovascular system, and the intervention management of these metabolic complications as well.
Androgen Antagonists
;
adverse effects
;
Blood Glucose
;
drug effects
;
Body Composition
;
drug effects
;
Cardiovascular System
;
drug effects
;
Cholesterol
;
blood
;
Humans
;
Male
;
Prostatic Neoplasms
;
blood
;
drug therapy
2.Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports.
Christer EHRNBORG ; Thord ROSÉN
Asian Journal of Andrology 2008;10(3):373-383
Growth Hormone (GH) is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombinant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH's rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span (24-36 hours) from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial.However, work with different approaches to develop an alternative, reliable test is ongoing.
Body Composition
;
Bone and Bones
;
drug effects
;
Doping in Sports
;
Growth Hormone
;
adverse effects
;
pharmacology
;
physiology
;
Humans
;
Lipolysis
;
Muscle, Skeletal
;
drug effects
;
physiology
3.Geriatric clinical pharmacology and clinical trials in the elderly.
Translational and Clinical Pharmacology 2014;22(2):64-69
The aging process is linked to changes in the physiological function of organs and changes in body composition that alter the pharmacokinetics of drugs and pharmacodynamic responses. Comorbidity and polypharmacy in the elderly decreases tolerability of drugs, leading to greater vulnerability to adverse drug reactions than that observed in younger adults. In geriatric pharmacotherapy, the general recommendation is dose reduction and slow titration, which is based on pharmacokinetic considerations and concern for adverse drug reactions, rather than clinical trial data. Older patients are under-represented in clinical trials. In the absence of evidence, extrapolation of risk-benefit ratios from younger adults to geriatric populations is not necessarily valid. Sound evidence through prospective clinical trials is essential, and geriatric societies, governments, and patient advocacy groups should collaborate to promote the inclusion of older people in clinical trials. It is believed that all involved in clinical trials have both an obligation and an opportunity to eliminate age discrimination in clinical trial practice.
Adult
;
Aged*
;
Ageism
;
Aging
;
Body Composition
;
Comorbidity
;
Drug Therapy
;
Drug-Related Side Effects and Adverse Reactions
;
Geriatrics
;
Humans
;
Patient Advocacy
;
Pharmacokinetics
;
Pharmacology, Clinical*
;
Polypharmacy
4.Effects of chromium nanoparticle dosage on growth, body composition, serum hormones and tissue chromium in Sprague-Dawley rats.
Long-ying ZHA ; Zi-rong XU ; Min-qi WANG ; Liang-ying GU
Journal of Zhejiang University. Science. B 2007;8(5):323-330
This 6-week study was conducted to evaluate the effects of seven different levels of dietary chromium (Cr) (0, 75, 150, 300, 450, 600, and 1 200 ppb Cr) in the form of Cr nanoparticle (CrNano) on growth, body composition, serum hormones and tissue Cr in Sprague-Dawley (SD) rats. Seventy male SD rats (average initial body weight of (83.2+/-4.4) g) were randomly assigned to seven dietary treatments (n=10). At the end of the trial, body composition was assessed via dual energy X-ray absorptiometry (DEXA). All rats were then sacrificed to collect samples of blood, organs and tissues for determination of serum hormones and tissue Cr contents. The results indicated that lean body mass was significantly increased (P<0.05) due to the addition of 300 and 450 ppb Cr from CrNano. Supplementation of 150, 300, 450, and 600 ppb Cr decreased (P<0.05) percent body fat significantly. Average daily gain was increased (P<0.05) by addition of 75, 150, and 300 ppb Cr and feed efficiency was increased (P<0.05) by supplementation of 75, 300, and 450 ppb Cr. Addition of 300 and 450 ppb Cr decreased (P<0.05) the insulin level in serum greatly. Cr contents in liver and kidney were greatly increased (P<0.05) by the addition of Cr as CrNano in the dosage of from 150 ppb to 1 200 ppb. In addition, Supplementation of 300, 450, and 600 ppb Cr significantly increased (P<0.05) Cr content in the hind leg muscle. These results suggest that supplemental CrNano has beneficial effects on growth performance and body composition, and increases tissue Cr concentration in selected muscles.
Animals
;
Body Composition
;
drug effects
;
Body Weight
;
drug effects
;
Chromium
;
administration & dosage
;
chemistry
;
pharmacokinetics
;
Dose-Response Relationship, Drug
;
Hormones
;
blood
;
Male
;
Nanoparticles
;
administration & dosage
;
ultrastructure
;
Organ Specificity
;
Particle Size
;
Rats
;
Rats, Sprague-Dawley
;
Tissue Distribution
5.Adipogenic and Lipolytic Effects of Ascorbic Acid in Ovariectomized Rats
Byoungjae KIM ; Kyung Min CHOI ; Hong Soon YIM ; Hyun Tae PARK ; Joung Han YIM ; Min Goo LEE
Yonsei Medical Journal 2018;59(1):85-91
PURPOSE: Ascorbic acid has been reported to have an adipogenic effect on 3T3-L1 preadipocytes, while evidence also suggests that ascorbic acid reduces body weight in humans. In this study, we tested the effects of ascorbic acid on adipogenesis and the balance of lipid accumulation in ovariectomized rats, in addition to long-term culture of differentiated 3T3-L1 adipocytes. MATERIALS AND METHODS: Murine 3T3-L1 fibroblasts and ovariectomized rats were treated with ascorbic acid at various time points. In vitro adipogenesis was analyzed by Oil Red O staining, and in vivo body fat was measured by a body composition analyzer using nuclear magnetic resonance. RESULTS: When ascorbic acid was applied during an early time point in 3T3-L1 preadipocyte differentiation and after bilateral ovariectomy (OVX) in rats, adipogenesis and fat mass gain significantly increased, respectively. However, lipid accumulation in well-differentiated 3T3-L1 adipocytes showed a significant reduction when ascorbic acid was applied after differentiation (10 days after induction). Also, oral ascorbic acid administration 4 weeks after OVX in rats significantly reduced both body weight and subcutaneous fat layer. In comparison to the results of ascorbic acid, which is a well-known cofactor for an enzyme of collagen synthesis, and the antioxidant ramalin, a potent antioxidant but not a cofactor, showed only a lipolytic effect in well-differentiated 3T3-L1 adipocytes, not an adipogenic effect. CONCLUSION: Taking these results into account, we concluded that ascorbic acid has both an adipogenic effect as a cofactor of an enzymatic process and a lipolytic effect as an antioxidant.
3T3-L1 Cells
;
Adipocytes/drug effects
;
Adipocytes/metabolism
;
Adipogenesis/drug effects
;
Animals
;
Antioxidants/pharmacology
;
Ascorbic Acid/pharmacology
;
Body Composition/drug effects
;
Body Weight/drug effects
;
Cell Differentiation/drug effects
;
Female
;
Fibroblasts/drug effects
;
Fibroblasts/metabolism
;
Lipolysis/drug effects
;
Mice
;
Ovariectomy
;
Rats, Sprague-Dawley
6.Isoflavone regulates lipid metabolism via expression of related genes in OVX rats fed on a high-fat diet.
Xiao-Lin NA ; Junko EZAKI ; Fumie SUGIYAMA ; Hong-Bin CUI ; Yoshiko ISHIMI
Biomedical and Environmental Sciences 2008;21(5):357-364
OBJECTIVETo investigate the effects of isoflavone on body weight, fat mass, and gene expression in relation to lipid metabolism.
METHODSThirty-six female SD rats were ovariectomized or sham-operated and fed on a high-fat diet. Two months later, abdominal incision was made, blood was collected to separate serum, and the liver and adipose tissue were immediately collected and weighed. Some portions of these tissues were frozen in liquid nitrogen and stored at -80 degrees C.
RESULTSOvariectomy (OVX) with a high-fat diet could induce obesity in rats, while treatment with isoflavone significantly inhibited the increase in body weight and fat mass in abdomen. Serum total cholesterol and leptin were significantly decreased in isoflavone group, compared with the OVX group. The mRNA expression of liver fatty acid synthase (FAS) in the OVX group was significantly higher than that in sham-operated group, while this difference was not observed in the isoflavone group. The mRNA expression of liver hormone-sensitive lipase (HSL) in the OVX rats tended to be lower than that in the sham-operated rats. Furthermore, a large amount of isoflavone maintained the mRNA expression at a sham level.
CONCLUSIONIsoflavone may prevent obesity induced by ovariectomy with a high-fat diet, in part by modulating gene expression related to lipid metabolism.
Adipose Tissue ; Animals ; Body Composition ; Body Weight ; Dietary Fats ; metabolism ; Feeding Behavior ; Female ; Gene Expression Regulation ; drug effects ; Isoflavones ; pharmacology ; Lipid Metabolism ; drug effects ; Liver ; anatomy & histology ; Organ Size ; Ovariectomy ; Rats ; Rats, Sprague-Dawley
7.Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism.
Mi Chung YOON ; Sun Hyo JEONG ; Christopher J NICOL ; Hyung Hee LEE ; Mi Young HAN ; Jung Jae KIM ; Yun Jeong SEO ; Chil Yeol RYU ; Goo Taeg OH
Experimental & Molecular Medicine 2002;34(6):481-488
To determine whether the PPARalpha agonist fenofibrate regulates obesity and lipid metabolism with sexual dimorphism, we examined the effects of fenofibrate on body weight, white adipose tissue (WAT) mass, circulating lipids, and the expression of PPARalpha target genes in both sexes of high fat diet-fed C57BL/6J mice. Both sexes of mice fed a high-fat diet for 14 weeks exhibited increases in body weight, visceral WAT mass, as well as serum triglycerides and cholesterol, although these effects were more pronounced among males. Feeding a high fat diet supplemented with fenofibrate (0.05% w/w) reduced all of these effects significantly in males except serum cholesterol level. Females on a fenofibrate-enriched high fat diet had reduced serum triglyceride levels, albeit to a smaller extent compared to males, but did not exhibit decreases in body weight, WAT mass, and serum cholesterol. Fenofibrate treatment resulted in hepatic induction of PPAR alpha target genes encoding enzymes for fatty acid beta-oxidation, the magnitudes of which were much higher in males compared to females, as evidenced by results for acyl-CoA oxidase, a first enzyme of the beta-oxidation system. These results suggest that observed sexually dimorphic effects on body weight, WAT mass and serum lipids by fenofibrate may involve sexually related elements in the differential activation of PPARalpha.
Adipose Tissue/drug effects/metabolism
;
Animals
;
Body Composition/drug effects
;
Body Weight/drug effects
;
Diet
;
Dietary Fats/pharmacology
;
Female
;
Gene Expression Regulation/drug effects
;
Lipids/blood/*metabolism
;
Liver/drug effects/metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Obesity/*metabolism/pathology
;
Organ Weight/drug effects
;
Procetofen/*pharmacology
;
Receptors, Cytoplasmic and Nuclear/*agonists
;
*Sex Characteristics
;
Time Factors
;
Transcription Factors/*agonists
8.The Effects of a High Fat Diet Containing Diacylglycerol on Bone in C57BL/6J Mice.
Han Seok CHOI ; Su Jin PARK ; Zang Hee LEE ; Sung Kil LIM
Yonsei Medical Journal 2015;56(4):951-960
PURPOSE: In epidemiologic and animal studies, a high fat diet (HFD) has been shown to be associated with lower bone mineral density (BMD) and a higher risk of osteoporotic fractures. Meanwhile, consuming a HFD containing diacylglycerol (DAG) instead of triacylglycerol (TAG) is known to offer metabolically beneficial effects of reductions in body weight and abdominal fat. The purpose of this study was to investigate the effects of a HFD containing DAG (HFD-DAG) on bone in mice. MATERIALS AND METHODS: Four-week-old male C57BL/6J mice (n=39) were divided into three weight-matched groups based on diet type: a chow diet group, a HFD containing TAG (HFD-TAG) group, and a HFD-DAG group. After 20 weeks, body composition and bone microstructure were analyzed using dual energy X-ray absorptiometry and micro-computed tomography. Reverse transcription-polymerase chain reaction (PCR) and real-time PCR of bone marrow cells were performed to investigate the expressions of transcription factors for osteogenesis or adipogenesis. RESULTS: The HFD-DAG group exhibited lower body weight, higher BMD, and superior microstructural bone parameters, compared to the HFD-TAG group. The HFD-DAG group showed increased expression of Runx2 and decreased expression of PPARgamma in bone marrow cells, compared to the HFD-TAG group. The HFD-DAG group also had lower levels of plasma glucose, insulin, total cholesterol, and triglyceride than the HFD-TAG group. CONCLUSION: Compared to HFD-TAG, HFD-DAG showed beneficial effects on bone and bone metabolism in C57BL/6J mice.
Absorptiometry, Photon
;
Adipogenesis
;
Animals
;
Body Composition
;
Body Weight
;
Bone Density/*drug effects
;
Bone Marrow Cells/metabolism
;
Diet, High-Fat/*adverse effects
;
Dietary Fats/*pharmacology
;
Diglycerides/administration & dosage/*adverse effects
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Osteogenesis/*drug effects
;
Real-Time Polymerase Chain Reaction
;
Triglycerides
;
X-Ray Microtomography
9.Growth hormone replacement therapy in adults with growth hormone deficiency; thrice weekly low dose administration.
Yoon Sok CHUNG ; Hyun Chul LEE ; Soo Kwan HWANG ; In Kyung PAIK ; Jong Ho LEE ; K B HUH
Journal of Korean Medical Science 1994;9(2):169-178
Recent reports on growth hormone (GH) therapy have shown that GH has various beneficial effects in GH deficient adults. In most of these studies, GH was administered daily. Because GH is still expensive and has to be delivered by subcutaneous injection, we studied the 6-month therapeutic effects of thrice weekly GH injection therapy and compared it with daily therapy. Twenty eight adult patients with GH deficiency were randomly assigned into group 1 (ten cases, thrice weekly injections of GH), group 2 (nine cases, daily injections), and group 3 (nine cases, placebo injections). Lean body mass, serum basal GH levels, and insulin-like growth factor 1 levels significantly increased after six months of GH therapy in both groups 1 and 2. According to computed tomography, the mean mid-thigh muscle mass significantly increased in group 1, while the visceral fat mass significantly decreased in group 2. GH levels significantly increased exercise rate-pressure product and hand grip strength only in group 1. These results suggest that thrice weekly injections of GH are as effective as daily injections in GH deficient adults.
Adult
;
Anthropometry
;
Body Composition/drug effects
;
Bone Density/drug effects
;
C-Peptide/blood
;
Carbohydrate Metabolism
;
Dose-Response Relationship, Drug
;
Drug Administration Schedule
;
Exercise/physiology
;
Female
;
Growth Hormone/*administration & dosage/adverse effects/*deficiency
;
Humans
;
Insulin/blood
;
Insulin-Like Growth Factor I/metabolism
;
Lipids/blood
;
Male
;
Middle Aged
;
Tomography, X-Ray Computed
10.Effect of Half-dose and Standard-dose Conjugated Equine Estrogens Combined with Natural Progesterone or Dydrogesterone on Components of Metabolic Syndrome in Healthy Postmenopausal Women: A Randomized Controlled Trial.
Wei XUE ; Yan DENG ; Yan-Fang WANG ; Ai-Jun SUN
Chinese Medical Journal 2016;129(23):2773-2779
BACKGROUNDMenopausal hormone therapy (MHT) has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen (CEE) and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women.
METHODSA prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups: Group A received CEE 0.3 mg/micronized progesterone (MP) 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student's t-test and analysis of variance.
RESULTSA total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline (all P < 0.05). Among the three groups, only Group C showed significantly increased triglycerides compared with baseline (1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P = 0.026). Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups.
CONCLUSIONSAmong Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.
TRIAL REGISTRATIONClinicalTrials.gov, NCT01698164; https://clinicaltrials.gov/ct2/show/NCT01698164?term=NCT01698164&rank=1.
Apolipoproteins B ; blood ; Blood Pressure ; drug effects ; Body Composition ; drug effects ; Dydrogesterone ; administration & dosage ; therapeutic use ; Estrogens, Conjugated (USP) ; administration & dosage ; therapeutic use ; Female ; Humans ; Insulin ; blood ; Lipoprotein(a) ; blood ; Metabolic Syndrome ; blood ; drug therapy ; Middle Aged ; Postmenopause ; Progesterone ; administration & dosage ; therapeutic use ; Triglycerides ; blood