Baseline characteristics and effects of growth hormone therapy over two years in younger and elderly adults with adult onset GH deficiency. Fifteen years of GH replacement improves body composition and cardiovascular risk factors Growth hormone (GH) replacement decreases serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor (statin) therapy Evaluation of coagulation and fibrinolytic parameters in adult onset GH deficiency and the effects of GH replacement therapy: a placebo controlled study. Moderate doses of hGH (0.64 mg/d) improve lipids but not cardiovascular function in GH-deficient adults with normal baseline cardiac function. Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy. Increased lipid peroxidation in adult GH-deficient patients: Effects of short-term GH administration Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency. Growth hormone treatment on atherosclerosis: results of a 5-year open, prospective, controlled study in male patients with severe growth hormone deficiency. Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A. Alterations of monocyte function in patients with growth hormone (GH) deficiency: effect of substitutive GH therapy. Lipid and apoprotein changes during atorvastatin up-titration in hemodialysis patients with hypercholesterolemia: a placebo-controlled study. Effects of growth hormone treatment on arginine to asymmetric dimethylarginine ratio and endothelial function in patients with growth hormone deficiency. One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults. Effects of GH on lipid peroxidation and neutrophil superoxide anion‐generating capacity in hypopituitary adults with GH deficiency The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial. Is Hypertriglyceridemia a Risk Factor for Atherosclerotic Cardiovascular Disease? A Simple Question with a Complicated Answer The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults. Randomized Controlled Trial on the Efficacy and Safety of Atorvastatin in Patients with Type 2 Diabetes on Hemodialysis (4D Study): Demographic and Baseline Characteristics Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on cardiovascular risk factors
CONTEXT The effects of GH replacement in elderly GH-deficient ( GHD ) adults are not well known . OBJECTIVE / DESIGN / PATIENTS In this prospect i ve , single-center , open-label study , baseline characteristics and the effects of 2-yr GH replacement were determined in 24 GHD adults above 65 yr of age and in 24 younger GHD patients ( mean age , 37 yr ; range , 27 - 46 yr ) . All patients had adult onset disease , and both groups were comparable in terms of the number of pituitary hormonal deficiencies , gender , body mass index , and waist/hip ratio . Duration of hypopituitarism was , however , longer in the elderly patients . RESULTS The mean maintenance dose of GH was 0.31 ( sem , 0.03 ) mg/d in the elderly GHD patients and 0.44 ( 0.04 ) mg/d in the younger patients . The less marked response in IGF-I sd score , total body fat , and extracellular water in the elderly patients lost significance when the dose of GH was accounted for in the statistical analyses . Despite the lower dose in the elderly GHD group , these patients had a more marked reduction in waist/hip ratio and serum low-density lipoprotein-cholesterol level , and these differences remained also after correction for duration of hypopituitarism . There was no difference at baseline or in responsiveness in lean mass , bone mineral density , and glucose homeostasis . CONCLUSIONS This study identifies elderly GHD adults as a GH-sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism .  GH replacement should therefore be considered in elderly GHD adults Objective Few studies have determined the effects of more than 5–10 years of GH replacement  in adults on  body composition and cardiovascular risk factors . Design / patients In this prospect i ve , single-center , open-label study , the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults ( 93 men ) with adult-onset GH deficiency ( GHD ) . Mean age was 50.5 ( range 22–74 ) years at study start .  Body composition was measured using dual-energy X-ray absorptiometry . Results The mean initial GH dose of 0.55 ( s.e.m . 0.03 ) mg/day was gradually lowered to 0.40 ( 0.01 ) mg/day after 15 years . The mean serum IGF1 SDS increased from −1.53 ( 0.10 ) at baseline to 0.74 ( 0.13 ) at study end ( P<0.001 vs baseline ) . Lean soft tissue ( LST ) increased to 3 % above the baseline level at study end ( P<0.001 ) . After a 9 % decrease during the first year of treatment ( P<0.001 vs baseline ) , body fat ( BF ) started to increase and had returned to the baseline level after 15 years . Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased . Fasting plasma glucose increased from 4.4 ( 0.1 ) at baseline to 4.8 ( 0.1 ) mmol/l at study end ( P<0.001 ) . However , blood HbA1c decreased from 5.0 ( 0.1 ) to 4.6 ( 0.1 ) % ( P<0.001 ) . Conclusions Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile . Fasting plasma glucose increased whereas blood HbA1c was reduced Objective Adult onset GH deficiency ( GHD ) is characterized by abnormalities of serum lipoprotein profiles and GH replacement results in favourable alterations in serum total and low density lipoprotein (LDL)‐cholesterol . Preliminary evidence has indicated that the effect of GH replacement in this respect may be additive to that of HMG CoA reductase inhibitor ( statin ) therapy . We have examined this possibility during prospect i ve follow‐up of adult onset hypopituitary patients enrolled in KIMS ( Pfizer International Metabolic Data base ) , a pharmacoepidemiological study of GH replacement in adult hypopituitary patients OBJECTIVE Increased cardiovascular mortality/morbidity observed in patients with hypopituitarism is ascribed to growth hormone deficiency ( GHD ) because of its unfavorable cardiovascular risk profile . Abnormalities in the coagulation system may also contribute to increased cardiovascular morbidity/mortality . To get a better insight into the role of hemostasis in GHD we assessed several hemostatic markers at baseline and after 6 months of GH replacement therapy ( GHRT ) . DESIGN - PATIENTS : Nineteen patients with adult onset GHD were enrolled ( twelve patients into the treatment and seven patients into the placebo group )  into the study . Platelet count , collagen/epinephrine closure time , collagen/ADP closure time , fibrinogen , prothrombin time ( PT ) , activated partial thromboplastin time ( aPTT ) , antithrombin III ( AT III ) , protein C activity , protein S activity , lupus anticoagulant , antiphospholipid antibody immunoglobulin M , and antiphospholipid antibody immunoglobulin G were measured at baseline and 6 months after treatment . RESULTS The investigated parameters in the groups were similar at baseline except for low protein S ( PS ) activity . Protein S deficiency was observed in three of the patients in the GH treatment group at baseline , however the PS activity values normalized following GHRT .  AT III and protein C activities decreased when compared to baseline values in the treatment group but not in the placebo group . CONCLUSIONS We observed protein S deficiency more frequent than seen in the general population and normalization of protein S activity and decreases , in other natural anticoagulants following GHRT . Further studies are required to underst and the impact of these changes in cardiovascular morbidity and mortality in this patient population CONTEXT Data regarding effects of lower-dose GH on cardiopulmonary function in GH-deficient ( GHD ) adults are limited . OBJECTIVES The objective was to assess effects of lower-dose GH on exercise capacity and echocardiographic parameters in GHD adults . DESIGN The study was a 6-month double-blind , placebo-controlled r and omized trial . SETTING The study was conducted at the General Clinical Research Center . PARTICIPANTS Thirty hypopituitary adults with GHD were studied . INTERVENTION Subjects were r and omized to recombinant human GH or placebo for 6 months , followed by open-label recombinant human GH for 12 months . MAIN OUTCOME MEASURES Primary endpoints were exercise duration , maximal oxygen consumption , and left ventricular ejection fraction . Secondary endpoints were echocardiographic indices of systolic and diastolic function , left ventricular mass , lipids , and body composition . RESULTS In the 6-month double-blind phase , mean GH dose was 0.64 mg/d . Mean IGF-I sd score increased from -4.5 to -1.0 . Exercise duration , maximal oxygen consumption , left ventricular ejection fraction , and other echocardiographic parameters were normal at baseline and did not change . GH decreased total and low-density lipoprotein cholesterol by 7.5 % ( P = 0.016 ) and 14.7 % ( P = 0.002 ) ( P = 0.04 vs. placebo ) . Mean lean body mass increased by 2.2 kg ( P = 0.004 ) , fat mass decreased by 1.7 kg ( P = 0.21 ) , and percent body fat decreased by 2.5 % ( P = 0.018 ) , although between-group changes were not significant . CONCLUSIONS Human GH did not improve exercise performance or echocardiographic parameters or decrease fat mass but significantly decreased total and low-density lipoprotein cholesterol , increased IGF-I , and increased lean body mass . These results indicate that responses to human GH are variable and should be assessed at baseline and during treatment OBJECTIVE Patients with growth hormone deficiency ( GHD ) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein ( HDL ) cholesterol concentrations , two lipid abnormalities usually accompanied by increased small dense LDL in the ' atherogenic lipoprotein phenotype ' ( ALP ) . In the present study , we directly investigated ( 1 ) whether hypopituitary patients with GHD have increased small dense LDL ; ( 2 ) whether growth hormone replacement therapy ( GHRT ) beneficially impact on such particles ; ( 3 ) the prevalence of ALP in GHD and GHRT patients . DESIGN AND METHODS In 14 hypopituitary patients with GHD ( 44 + /- 13 years , body mass index ( BMI ) 27 + /- 3 ) before and after 4 months of GHRT , and in 11 healthy age- and BMI -matched controls we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis . RESULTS Compared with controls , GHD showed increased triglycerides ( P = 0.0024 ) , similar total and LDL cholesterol levels and a tendency towards reduced HDL cholesterol concentrations ( P = 0.0894 ) . GHRT reduced total and LDL cholesterol levels ( P = 0.0303 and 0.0120 respectively ) , but no effect was found on triglycerides and HDL cholesterol levels . LDL size was unchanged in GHD versus controls ( 269 + /- 9 vs 274 + /- 6 A , P = ns ) , but LDL subclass analysis revealed a shift towards more dense particles ( P = 0.0046 ) . GHRT had no significant impact on LDL size and subclasses . The prevalence of ALP was 14 % in GHD and 7 % in GHRT . CONCLUSIONS In GHD patients , individual features of ALP ( including increased small dense LDL ) may be common , but complete ALP is relatively uncommon . Short-term replacement therapy seems to be ineffective on such lipid alterations , but the effect of a longer GHRT remains to be assessed Objective : Adult GH deficiency ( GHD ) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality . Oxidative stress appears to play an important role in early atherogenesis . Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium . Its concentrations are increased in GHD , but the association between this abnormality and oxidative stress is still unclear , due to the discordant results yielded by the few available studies . Design and methods : In 13 GHD patients , plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH ( rhGH ) and compared with those of 13 age- and sex-matched controls . In the same subjects , the so-called “ lag-time ” , an index of anti-oxidant activity and thus of plasma oxidative balance , was also measured using a fluorescence kinetics method . Results : Before treatment , peroxide levels were significantly higher in patients than in controls ( 374.0±31.52 vs 268.0±8.51 U.C. , p<0.01 ) , whereas the lag-time was significantly lower ( 113.0±10.70 vs 168.0±7.80 min , p<0.01 ) . RhGH administration to patients result ed both in a significant decrease in lipid peroxide levels ( from 374.0±31.52 to 336.0±33.17 U.C. , p<0.01 ) and a significant prolongation of lag-time ( from 113.0±10.70 to 144.0±15.00 min , p<0.01 ) . After treatment , both parameters were no longer significantly different in patients and controls . Lagtime and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients . After replacement therapy , however , lag-time was positively ( r2= 0.62 , p<0.01 ) , and peroxide levels negatively ( r2=0.41 , p<0.05 ) , correlated with IGF-I levels . Conclusions : These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former . This abnormality , likely contributing to the increased atherogenic risk of GHD patients , is corrected by short-term GH administration at a dose able to increase , although not to fully normalize , IGF-I levels CONTEXT GH secretion and response to GH replacement are gender-related . OBJECTIVE The objective of this study was to investigate the effects of GH deficiency ( GHD ) and replacement on the cardiovascular system according to gender . DESIGN The design was open and prospect i ve . SETTING The study was conducted at a university hospital . SUBJECTS Subjects included 36 severe adult-onset GHD patients ( 18 men , 20 women , aged < 45 yr ) ; 36 gender- , age- , and body mass index-matched healthy subjects served as controls . INTERVENTIONS Subjects received GH replacement at a median dose of 6.5 microg/kg.d in men and 7.7 microg/kg.d in women for 2 yr . MAIN OUTCOME MEASURES Homeostasis model assessment index , total to HDL cholesterol ratio , fibrinogen and C-reactive protein levels , left ventricular mass index , blood pressure , heart rate , diastolic filling , and systolic function at rest and at peak exercise and intima-media thickness ( IMT ) at common carotid arteries were measured . RESULTS Basal prevalence and /or degree of insulin resistance , lipid alterations , compromised cardiac function , and IMT were similar in women and men . Diastolic dysfunction was more prevalent in men ( 61 vs. 25 % , P = 0.036 ) . After GH replacement , IGF-I levels normalized in all patients . Lipid profile , fibrinogen , and C-reactive protein levels normalized in all cases . The total to HDL ratio ( P = 0.04 ) was higher in women than men . The homeostasis model assessment index persisted higher in GHD patients than controls and decreased only in GHD men ( P = 0.017 ) . Left ventricular mass index normalized during treatment in both women and men , abnormal diastolic function persisted in three women ( P = 0.031 ) , and abnormal systolic performance persisted in six women and one man ( P = 0.13 ) . IMT decreased similarly in women and men , persisting higher than in controls . Exercise performance normalized in all . CONCLUSIONS Two-year GH replacement has similar beneficial effects on cardiac and exercise performance and atherosclerosis in women and men with severe GHD BACKGROUND Severe GH deficiency ( GHD ) is associated with , increased cardiovascular risk and intima-media thickness ( IMT ) at major arteries . OBJECTIVE The objective of the study was to investigate the 5-yr effects of GH replacement on common carotid IMT and insulin resistance syndrome ( IRS ) ( at least two of the following : triglycerides levels > or = 1.7 mmol/liter , high-density lipoprotein-cholesterol levels < or = 1.0 mmol/liter , blood pressure above 130/85 mm Hg , fasting glucose 6.1 - 7 or 2 hr after glucose 7.7 - 11.1 mmol/liter ) . DESIGN This was an interventional , open , prospect i ve , controlled study . PATIENTS Patients included 35 men with severe GHD and 35 age-matched healthy men as controls . INTERVENTION All patients received st and ard replacement therapy ; GH replacement was added in 22 patients ( group A ) and refused by 13 others ( group B ) . MEASUREMENTS Five-year changes in IMT and IRS prevalence were measured . RESULTS At baseline , IMT was higher in the patients with ( P < 0.001 ) and without IRS ( P = 0.004 ) than in controls . Eighteen patients ( 51.4 % ) and two controls ( 5.7 % ; P < 0.0001 ) had IRS . At study end , use of lipid-lowering drugs ( 92.3 , vs. 13.6 and 34.3 % , P < 0.0001 ) , glucose-lowering drugs ( 69.2 vs. 31.4 and 22.7 % ; P = 0.016 ) , and antihypertensive drugs ( 61.5 vs. 20.0 and 4.5 % ; P < 0.0001 ) was higher in group B patients than controls and group A patients . IGF-I levels normalized in all group A patients and remained lower than -1 sd score in 77 % of group B patients . IMT significantly decreased only in group A and significantly increased in controls and nonsignificantly in group B patients . IRS prevalence significantly reduced only in group A patients . CONCLUSIONS Severely hypopituitary GHD men have more frequently increased IMT at common carotid arteries and IRS than controls . After 5 years , only in GH replaced patients , IMT and prevalence of IRS decreased OBJECTIVE  GH deficiency ( GHD ) in adults is associated with adverse effects on metabolism and increased cardiovascular risk . Pregnancy-associated plasma protein-A ( PAPP-A ) is a protease that promotes IGF-I availability in vascular tissues . PAPP-A levels appear to correlate with carotid intima-media thickness and have been proposed as an early predictor of cardiac events . The aim of our study was to evaluate PAPP-A levels in GHD adults at baseline and after GH replacement and correlate them with changes in body composition , lipid profile , glucose homeostasis , inflammatory markers and in leptin and adiponectin . PATIENTS AND METHODS Fourteen GHD adults were evaluated at baseline and after 1 year of GH therapy .  All patients were compared at baseline with 28 age- , sex- and body mass index ( BMI ) -matched control subjects . RESULTS At baseline , GHD adults showed higher PAPP-A levels ( P=0.03 ) and higher leptin ( P=0.04 ) , fibrinogen ( P=0.002 ) and highly sensitive C-reactive protein ( P=0.01 ) values than controls . Therapy with GH  reduced PAPP-A ( P=0.03 ) and fibrinogen levels ( P=0.002 ) while increased BMI ( P=0.01 ) and reduced waist-hip ratio ( WHR ; P=0.05 ) were observed . Insulin and homeostasis model assessment of insulin resistance index increased after treatment ( P<0.004/P=0.007 ) , without changes in leptin or adiponectin levels . PAPP-A values correlated positively with BMI and WHR and negatively with adiponectin before and after treatment , with no correlation with glucose homeostasis parameters , lipid profile or leptin . CONCLUSIONS Our study suggests that PAPP-A expression is increased in GHD adults , and that 1 year of GH replacement therapy is able to reduce PAPP-A levels in this population . However , further studies are required to determine whether this decrease correlates with an improvement in atherosclerosis GH deficiency ( GHD ) is associated with increased prevalence of atherosclerosis and cardiovascular morbidity . Because monocytes play a crucial role in the development of atherosclerosis , we investigated in the present study the effect of GH deficiency and subsequent GH replacement on monocytic function in hypopituitary subjects . Twelve patients were r and omized to receive GH replacement therapy ( either 3 or 6 microg/kg x day , s.c . ) for 3 months . Plasma levels and monocyte production of cytokines and monocyte adhesion to endothelium were determined in controls and patients with GHD before and after GH treatment . Before GH therapy , patients with GHD had increased basal plasma tumor necrosis factor-alpha ( TNF alpha ; 220 % over control values ; P = 0.004 ) and interleukin-6 ( IL-6 ; 340 % over control values ; P 0.0009 ) levels . Basal monocyte production of both cytokines was also significantly higher in patients with GHD [ 484 % over control values for TNF alpha ( P = 0.0007 ) ; 1479 % over control values for IL-6 ( P = 0.035 ) ] . GH treatment for 3 months led to a reduction in plasma TNF alpha ( 135 % over control values ; P = 0.03 , pre- vs. post-GH therapy ) , monocyte TNF alpha production ( 204 % over control values ; P = 0.01 ) , plasma IL-6 ( 219 % over control values ; P = 0.07 ) , and monocyte IL-6 production ( 448 % over control values ; P = 0.01 ) . Plasma TNF alpha levels positively correlated with monocyte TNF alpha production in patients with GHD both before and after GH therapy ( P = 0.003 and P = 0.049 , respectively ) . A positive correlation ( P = 0.0003 ) was also observed between monocyte TNF alpha production and monocyte IL-6 production . There were no correlations between these plasma cytokine levels or monocyte cytokine production and parameters of body composition , lipid profile , or IGF-I and IGF-binding protein-3 levels . Before GH treatment , adhesiveness of monocytes to cultured aortic endothelial cells was also enhanced . This alteration was not reversed by GH administration . In conclusion , our results demonstrate that markers of monocyte activation are increased in patients with GHD and that GH replacement partly reduces these abnormalities . Reduction of cellular activation of monocytes by GH therapy could potentially contribute to reduce the risk of cardiovascular events in patients with GHD BACKGROUND Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich , apoprotein B-containing " remnant " lipoproteins , small dense low-density lipoprotein , and low levels of high-density lipoprotein . They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin , a potent , broadacting lipid regulator . This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients , to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup . METHODS In this r and omized , placebo-controlled , double-blind study in hemodialysis patients with hypercholesterolemia ( n = 42 , mean total cholesterol 243 + /- 33 mg/dl ( 6.3 + /- 0.8 mmol/l ) ) , the efficacy of 4-weekly increasing doses of atorvastatin ( 10 - 40 mg daily ) was investigated . Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions . RESULTS Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin ( total cholesterol -33 % , low-density lipoprotein cholesterol -43 % after 12 weeks ) , while high-density lipoprotein cholesterol remained unchanged . Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg , while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III . At week 12 , the fraction of small dense low-density lipoprotein was significantly reduced from 23 % - 18 % , and apoprotein B-containing intermediate-density lipoproteins were no longer detectable . CONCLUSION In conclusion , atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis .  Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated . Further prospect i ve studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality Patients with growth hormone deficiency ( GHD ) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events . An increase in asymmetric dimethylarginine ( ADMA ) levels previously found in GHD patients could promote premature atherosclerosis . The aim of this study was to determine whether 6-month growth hormone ( GH ) replacement therapy was able to decrease ADMA levels and ameliorate endothelial dysfunction .  Thirty-one GHD patients were studied before and after 6 months of GH ( 4 microg/[kg d ] , daily ) replacement therapy . Reduced pretreatment levels of serum insulin-like growth factor ( IGF ) 1 were normalized during GH treatment ( 88.2 + /- 62.5 to 191.7 + /- 80.3 ng/mL , P < .0001 ) . After 6 months of GH replacement , plasma cyclic guanosine monophosphate levels significantly increased ( 2.14 + /- 0.52 to 3.54 + /- 1.2 ng/mL , P < .0001 ) , serum ADMA levels were significantly decreased ( 0.65 + /- 0.1 vs 0.59 + /- 0.11 mumol/L , P < .05 ) , and arganine ( Arg ) to ADMA ratio was significantly higher ( 155 + /- 53 vs 193 + /- 61 , P < .01 ) . No changes were observed for plasma nitric oxide end products ( nitrite and nitrate ) levels after GH treatment ( 21.9 + /- 14.9 vs 24.1 + /- 19.0 mumol/L , not significant ) . Basal forearm blood flow remained unchanged , whereas reactive hyperemia increased from 7.30 + /- 5.31 mL/100 mL forearm per minute before GH therapy to 13.18 + /- 7.30 mL/100 mL forearm per minute after 6 months of therapy ( P < .001 ) . There was a positive correlation between IGF-1 and cyclic guanosine monophosphate ( r = 0.73 , P < .0001 ) , IGF-1 and reactive hyperemia ( r = 0.63 , P < .0001 ) , and IGF-1 and Arg/ADMA ratio ( r = 0.44 , P < .01 ) . Conversely , a negative correlation was found between IGF-1 and ADMA levels ( r = -0.41 , P < .02 ) . At the end of the study period , fat-free mass , plasma glucose , and hemoglobin A(1c ) levels significantly increased , even if they were still in the reference range , suggesting moderate alteration of glucose metabolism . In conclusion , in GHD patients , GH replacement contributes to decreased , to some extent , cardiovascular risk , reducing ADMA levels and improving Arg/ADMA ratio and endothelial dysfunction OBJECTIVE We have studied the effects on body composition and metabolism of a fixed low dose of growth hormone ( GH ) , 0.6 IU ( 0.2 mg)/day , administered for 12 months to GH-deficient ( GHD ) adults . DESIGN AND METHODS Prospect i ve open-label study , using 18 GHD patients ( 11 women , 7 men ; aged 21 - 58 years ) . All investigations were performed at baseline and after 12 months . Body composition was determined by dual energy X-ray absorptiometry . RESULTS Total body fat decreased ( -1.74+/-2.87 % ) and lean body mass ( LBM ) increased ( 1.27+/-2.08 kg ) after therapy ( P < 0.05 ) . Changes in truncal fat did not reach statistical significance , but a decrease varying from 0.72 to 2.78 kg ( 1 to 8.7 % ) was observed in 13 ( 72 % ) patients . Bone mineral density ( BMD ) increased at lumbar spine , total femur and femoral neck ( P < 0.05 ) . Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy ( P < 0.05 ) , and their changes were directly associated with values at baseline . Insulin levels increased and the insulin resistance index worsened at 12 months ( P < 0.05 ) . Median IGF-I s.d . score was -4.30 ( range , -11.03 to -0.11 ) at baseline and -1.73 ( range , -9.80 to 2.26 ) at 12 months . Normal age-adjusted IGF-I levels were obtained with therapy in 5 of 11 patients who had low IGF-I levels at baseline . Changes in IGF-I levels were not correlated with any biological end point , except changes in LBM ( r = 0.53 , P = 0.02 ) . Side effects were mild and disappeared spontaneously . CONCLUSIONS One-year of a fixed low-dose GH regimen in GHD adults result ed in a significant reduction in body fat , total cholesterol and LDL-cholesterol , and a significant increase in LBM and BMD at lumbar spine and femur , regardless of normalization of IGF-I levels . This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index objectives  Untreated growth hormone deficiency ( GHD ) is implicated in the increased cardiovascular risk associated with adult hypopituitarism . Oxidative stress , predisposing to lipid peroxidation , may be an important mediator of endothelial dysfunction , a pro‐atherogenic state associated with adult GHD BACKGROUND Adult GHD syndrome is associated with clustering of adverse cardiovascular ( CV ) risk factors such as abnormal body composition , dyslipidemia , insulin resistance and abnormal haemostatic factors . There is a wealth of evidence linking CV events with elevated levels of inflammatory markers ( hs-CRP and IL-6 ) in the general population ; however data on their abnormalities in GHD and specially the effects of GH replacement ( GHR ) on these inflammatory markers are limited . OBJECTIVE To study the effects of GHR on inflammatory markers , glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease . DESIGN Fifteen hypopituitary adults ( 11 males , mean age 48.5 years ) with recently diagnosed , severe GHD were recruited . Patients received GHR ( in addition to other pituitary hormone replacements ) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels . Weight , waist hip ratio ( WHR ) , body composition , fasting plasma glucose and insulin , insulin resistance index ( HOMA-IR ) , fasting serum lipid levels , hs-CRP , IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR . RESULTS GHR result ed in a physiological increase in IGF-1 SDS [ median -0.6 to + 0.39 , P<0.0001 ] , improved quality of life ( mean pre-treatment AGHDA score 16 vs. post-treatment score 7 , P<0.0001 ) and reduction in WHR ( 0.94 vs. 0.92 , P=0.01 ) . There were no significant changes in body weight and composition . Levels of hs-CRP ( log transformed , mean ( SD ) ) were significantly reduced following GHR ( pre 1.21 ( 0.9 ) vs. post 0.27 ( 0.9 ) , P<0.0001 ) but TNF-alpha and IL-6 levels remained unchanged . Fasting glucose ( mmol/L ) [ 4.6 ( 0.1 ) vs. 5.1 ( 0.1 ) , P=0.003 ] , fasting insulin ( muU/mL ) [ 9.4 ( 8.1 ) vs. 12.1 ( 9.2 ) , P=0.03 ] and HOMA-IR [ 1.2 ( 1.0 ) vs. 1.5 ( 1.1 ) P=0.02 ] ( all pre-GHR vs. post-GHR and mean ( SD ) ) significantly increased following GHR indicating increased insulin resistance . Significant improvements were noted in fasting LDL-cholesterol ( LDL-C ) and HDL-cholesterol ( HDL-C ) levels following GHR [ 3.4 ( 0.9 ) vs. 2.9 ( 0.7 ) , P=0.03 and 1.2 ( 0.2 ) vs. 1.3 ( 0.2 ) , P=0.02 , respectively ] ( all pre-GHR vs. post-GHR and mean ( SD ) ) . Levels of total cholesterol and triglycerides did not change following GHR . CONCLUSIONS Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD result ed in favourable changes in hs-CRP , WHR , fasting LDL-C and HDL-C levels all of which are recognised CV risk markers . However , there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR , monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population CONTEXT Polycystic ovary syndrome ( PCOS ) is associated with the metabolic syndrome and , consequently , with a potentially increased risk of cardiovascular disease ( CVD ) and related mortality later in life . Studies regarding CVD and mortality in PCOS women well into the postmenopausal age are lacking . OBJECTIVE Our objective was to examine whether postmenopausal PCOS women differ from controls regarding cardiovascular risk factors , myocardial infa rct ion ( MI ) , stroke and mortality . DESIGN AND SETTING We conducted , at a university hospital , a prospect i ve study of 35 PCOS women ( 61 - 79 yr ) and 120 age-matched controls . The study was performed 21 yr after the initial study . PARTICIPANTS Twenty-five PCOS women ( Rotterdam criteria ) and 68 controls participated in all examinations . Data on morbidity were based on 32 of 34 PCOS women and on 95 of 119 controls . INTERVENTIONS INTERVENTIONS included reexamination , interviews , and data from the National Board of Health and Welfare and from the Hospital Discharge Registry . MAIN OUTCOME MEASURES Blood pressure , glucose , insulin , triglycerides , total cholesterol , high- and low-density lipoprotein , apolipoprotein A1 and B , fibrinogen , and plasminogen activator inhibitor antigen were studied . Incidences of MI , stroke , hypertension , diabetes , cancer , cause of death , and age at death were recorded . RESULTS PCOS women had a higher prevalence of hypertension ( P = 0.008 ) and higher triglyceride levels ( P = 0.012 ) than controls . MI , stroke , diabetes , cancer , and mortality prevalence was similar in the two cohorts with similar body mass index . CONCLUSIONS The well-described cardiovascular/metabolic risk profile in pre- and perimenopausal PCOS women does not entail an evident increase in cardiovascular events during the postmenopausal period Abdominal obesity is associated with blunted GH secretion and a cluster of cardiovascular risk factors that characterize the metabolic syndrome . GH treatment in abdominally obese men reduces visceral adipose tissue and has beneficial effects on the metabolic profile . There are no long-term data on the effects of GH treatment on postmenopausal women with abdominal obesity . Forty postmenopausal women with abdominal obesity participated in a r and omized , double-blind , placebo-controlled , 12-month trial with GH ( 0.67 mg/d ) . The primary aim was to study the effect of GH treatment on insulin sensitivity . Measurements of glucose disposal rate ( GDR ) using a euglycemic , hyperinsulinemic glucose clamp ;  abdominal fat , hepatic fat content , and thigh muscle area using computed tomography ; and total body fat and fat-free mass derived from (40)K measurements were performed at baseline and at 6 and 12 months . GH treatment reduced visceral fat mass , increased thigh muscle area , and reduced total and low-density lipoprotein cholesterol compared with placebo .  Insulin sensitivity was increased at 12 months compared with baseline values in the GH-treated group . In the GH-treated group only , a low baseline GDR was correlated with a more marked improvement in insulin sensitivity ( r = -0.68 ; P < 0.001 ) . A positive correlation was found between changes in GDR and liver attenuation as a measure of hepatic fat content between baseline and 12 months ( r = 0.7 ; P < 0.001 ) in the GH-treated group . In postmenopausal women with abdominal obesity , 1 yr of GH treatment improved insulin sensitivity and reduced abdominal visceral fat and total and low-density lipoprotein cholesterol concentrations . The improvement in insulin sensitivity was associated with reduced hepatic fat content BACKGROUND Growth hormone-deficient adults have increased cardiovascular mortality . Growth hormone replacement may affect cardiovascular risk . Inflammation plays an important role in atherosclerosis , and inflammatory markers are predictive of cardiovascular events . OBJECTIVE To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors . DESIGN R and omized , single-blind , placebo-controlled trial . PATIENTS 40 men with adult-onset growth hormone deficiency . INTERVENTION Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level . MEASUREMENTS Anthropometric , hemoglobin A1c , and central fat values were assessed every 6 months . Levels of glucose , insulin , insulin-like growth factor I , and lipids were measured at 1 , 3 , 6 , 12 , and 18 months . C-reactive protein , serum amyloid polypeptide A , inteleukin-6 , and lipoprotein(a ) levels were determined at baseline and 6 and 18 months . RESULTS C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients ( differences between groups , -1.9 + /- 0.6 mg/L [ P = 0.0027 ] and -1.3 + /- 0.5 ng/L [ P = 0.013 ] , respectively ) . Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance ( difference between groups , -2.4 + /- 1.2 mg/L ; P = 0.056 ) . Serum cholesterol levels , low-density lipoprotein cholesterol levels , and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients ( differences between groups , -0.86 + /- 0.17 mmol/L [ -33.2 + /- 6.6 mg/dL ] [ P < 0.001 ] , -0.63 + /- 0.20 mmol/L [ -24.5 + /- 5.9 mg/dL ] [ P < 0.001 ] , and -0.56 + /- 0.26 [ P = 0.040 ] , respectively ) , but the decrease was not maintained from month 6 to month 18 . Lipoprotein(a ) levels increased ( difference between groups , 22.0 + /- 8.0 mg/L ; P = 0.0096 ) . Short-term increases occurred in glucose levels , insulin levels , and insulin-to-glucose ratios ( differences between groups , 0.54 + /- 0.16 mmol/L [ 9.6 + /- 2.8 mg/dL ] [ P = 0.0018 ] , 37.9 + /- 9.6 pmol/L [ P < 0.001 ] , and 6.0 + /- 1.8 [ P = 0.0025 ] , respectively ) , but only the increase in glucose level was maintained over the long term ( difference between groups , 0.56 + /- 0.17 mmol/L [ 10.0 + /- 3.1 mg/dL ] ; P = 0.0026 ) . Hemoglobin A1c values did not change . Truncal fat-to-total fat ratios decreased ( difference between groups , -0.018 + /- 0.007 ; P = 0.0087 ) . CONCLUSIONS Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers , decreases central fat , and increases lipoprotein(a ) and glucose levels without affecting lipid levels The role of hypertriglyceridemia in the pathogenesis of atherosclerotic cardiovascular disease has been controversial for many years [ 1 , 2 ] . It remains so despite extensive investigation by basic scientists , clinicians , and epidemiologists . The lack of resolution of this issue derives mainly from the complexity inherent in the lipoprotein transport system [ 3 ] . Although it is not possible to either unravel all of this complexity or resolve the controversy here , I attempt to provide a balanced review of the relevant literature , concluding with a suggested approach to the evaluation and treatment of the many patients who have elevated plasma triglyceride levels . I focus on the lipid aspects of this issue , but it should not be forgotten that elevated triglyceride levels have been associated with several abnormalities of the clotting-fibrinolytic systems [ 4 ] . Triglyceride does not accumulate in the vessel wall . Its atherogenicity must be based , therefore , on the association , within lipoproteins , between triglyceride and cholesterol , the lipid that does accumulate in atherosclerotic plaque . Thus , proponents of an association between hypertriglyceridemia and atherosclerotic cardiovascular disease must postulate that disordered metabolism of the triglyceride-rich lipoproteins-very low density lipoprotein ( VLDL ) or chylomicron or both-is proatherogenic . This concept is not extreme : Even the well-accepted link between cholesterol and atherosclerotic cardiovascular disease relies on the accumulation of low-density lipoprotein ( LDL ) cholesterol , not simply plasma cholesterol , in lesions . The concept that several lipoprotein species can contribute cholesterol to lesion formation is not , therefore , unreasonable . Indeed , ample studies have shown that chylomicron remnants ( the lipoprotein formed from chylomicrons after removal of much , but not all , of the chylomicron triglyceride ) and VLDL ( or its remnants ) enter the subendothelial space of the vessel wall [ 5 , 6 ] . These lipoproteins can also be internalized by monocyte macrophages , result ing in formation of foam cells . Recent studies in transgenic mice dramatically demonstrated the atherogenic potential of VLDL and chylomicron remnants , even when the mice were consuming normal chow diets [ 7 ] . If the delivery of cholesterol to the vessel wall by triglyceride-rich lipoproteins is , in fact , involved in the pathophysiology of atherosclerotic cardiovascular disease , epidemiologic data should show links between hypertriglyceridemia and this disease . When examining the role of triglyceride by univariate analyses , most prospect i ve cohort studies have shown a positive relation between triglyceride levels and risk [ 2 ] . In multivariate analyses , however , triglyceride has often been shown to no longer be significantly associated with risk . Important exceptions may be seen in women with hypertriglyceridemia and patients with diabetes . I focus here only on three potential confounders of this statistical approach : the inverse relation between plasma levels of triglyceride and high-density lipoprotein ( HDL ) cholesterol , the potential atherogenicity of postpr and ial hypertriglyceridemia , and the biochemical and physical heterogeneity of triglyceride-rich lipoproteins . High-density lipoprotein cholesterol is widely accepted as being protective against atherosclerotic cardiovascular disease [ 8 ] . The evidence has primarily been derived from prospect i ve cohort studies and from secondary analyses of intervention trials in which lowering LDL cholesterol levels was the primary goal . The leading theory invokes a role for HDL in the reverse cholesterol transport pathway , whereby cellular cholesterol can associate with HDL ; in turn , the latter delivers cellular cholesterol to the liver for excretion . In most population s , triglyceride and HDL cholesterol levels are inversely related . Thus , analyses of triglyceride as a risk factor that use HDL cholesterol as a covariate will be confounded by the lack of independence of the two variables ; both of these variables affect risk for atherosclerotic cardiovascular disease , but in opposite directions . Although recent studies in gene-knockout and transgenic mice support direct antiatherogenic roles for HDL [ 9 , 10 ] , the physiologic basis for the inverse relation between plasma levels of triglyceride and HDL cholesterol suggests that low HDL cholesterol levels may simply reflect proatherogenic disorders of triglyceride-rich lipoproteins . Increased levels of VLDL and chylomicrons stimulate the exchange of their triglyceride for cholesterol in HDL . Although this exchange , which is mediated in plasma by cholesteryl ester transfer protein [ 11 ] , may be an alternate pathway for reverse cholesterol transport ( with delivery of the cholesterol to the liver by VLDL and chylomicron remnants ) , movement of HDL cholesterol into triglyceride-rich lipoproteins could also result in the delivery of some cholesterol back to peripheral cells . Over time , such short-circuiting of the reverse cholesterol transport system could result in accumulation of cholesterol in tissues , including the arterial wall . Essentially all of the epidemiologic data linking lipids and lipoproteins to risk for atherosclerotic cardiovascular disease are based on fasting levels [ 2 ] . Plasma levels of triglycerides vary widely throughout the day , however , because we absorb many grams of dietary fat after each meal . In the past decade , evidence for the atherogenicity of postpr and ial triglyceride-rich lipoproteins has increased . Several recent studies have indicated that postpr and ial levels of triglyceride and chylomicron remnants are predictive of the presence of atherosclerotic cardiovascular disease even when other risk factors , including HDL cholesterol , are considered [ 12 , 13 ] . The role of triglyceride in atherogenesis might have been more readily demonstrated if epidemiologic studies had used nonfasting blood levels . Another important reason for the difficulty in linking triglyceride levels to risk for atherosclerotic cardiovascular disease is the physical and biochemical heterogeneity of VLDL and chylomicrons . In particular , the size , number , and cholesterol content of these lipoproteins can vary greatly among individual persons . Size is important because very large particles can not easily pass into the subendothelial space , the site of initiation of the atherogenic process . The number of triglyceride-rich particles in the bloodstream is also crucial , in part because the presence of more particles increases the probability that they will enter and be retained in the vessel wall , and in part because for any triglyceride level , more particles mean smaller , more atherogenic particles . Finally , the cholesterol content of the triglyceride-rich lipoproteins can vary significantly , and persons with more cholesterol-enriched particles will be at greater risk . Because of differences in the size , number , and cholesterol content of triglyceride-rich particles , patients with similar levels of plasma triglyceride may have very different risks for atherosclerotic cardiovascular disease . So what is the clinician to do with the not uncommon , middle-aged patient who has hypertriglyceridemia ? The National Cholesterol Education Program ( NCEP ) has not developed precise guidelines on which to base therapy [ 14 ] . Moreover , neither of the reports of two intervention trials gives a clearcut answer . The Helsinki Heart Study subgroup analysis [ 15 ] indicated that patients who had pure hypertriglyceridemia and were receiving  gemfibrozil had a risk reduction similar to that of patients with either pure hypercholesterolemia or combined hyperlipidemia ; however , the size of the subgroup was small . In the Stockholm Ischemic Heart Disease Study [ 16 ] , the reductions in the rate of coronary events seen in patients treated with clofibrate and niacin correlated with reductions in triglyceride levels , but neither HDL nor LDL cholesterol levels were measured . In the face of these suggestive but incomplete data , one approach would be to use the NCEP guidelines , particularly focusing on the presence of other risk factors commonly associated with hypertriglyceridemia ( hypertension , diabetes , low HDL cholesterol levels ) to guide the intensity of therapy focused on LDL cholesterol . Thus , if the patient is a man older than 45 years of age or a postmenopausal woman , it is likely that he or she will have two or more of the risk factors listed in the NCEP guidelines [ 14 ] and will require an LDL cholesterol level less than 130 mg/dL. If the patient has clinical atherosclerotic cardiovascular disease , an LDL cholesterol level less than 100 mg/dL would be the goal . When a patient with hypertriglyceridemia but not clinical atherosclerotic cardiovascular disease has an LDL cholesterol  less than 130 mg/dL , however , the NCEP guidelines do not provide clear direction for therapy , regardless of the number of additional risk factors . Here , the LDL : HDL ratio might be helpful ; both the Helsinki Study [ 17 ] and the Procam Study [ 18 ] indicated that patients with ratios exceeding 5.0 and triglyceride levels exceeding 200 mg/dL had markedly increased risk . It must be understood , however , that no data support the value of further lowering LDL cholesterol levels that are already less than 130 mg/dL in patients without clinical atherosclerotic cardiovascular disease . Measurement of apoprotein B levels ( when st and ardization programs are widely available ) might be of particular benefit in these patients [ 19 ] . Because of the multiple links between elevated triglyceride levels and risk for atherosclerotic cardiovascular disease , it seems prudent to screen for the presence of hypertriglyceridemia when determining a patient 's risk for atherosclerotic cardiovascular disease . A therapeutic program for hypertriglyceridemia should obviously include diet , exercise , and weight loss programs : These are even more important in patients with hypertriglyceridemia than in persons with GH deficiency is associated with increased cardiovascular morbidity , which may be determined by alterations in vascular risk factors . We report the effect of partially treated hypopituitarism and subsequent GH replacement ( mean dose , 0.2 IU/kg.week ) on putative cardiovascular risk factors in 22 nondiabetic hypopituitary subjects in a 6-month , double blind , controlled study ( active/placebo ratio , 11:11 ) . All patients were subsequently treated with GH for a further 6 months .  Total fat , percent body fat , and central fat were measured by dual energy x-ray absorptiometry .  The hypopituitary patients had increased percent fat ( P = 0.03 ) and central fat ( P < 0.01 ) compared with body mass index-matched controls . Before GH treatment , fasting ( total ) and specific insulin positively correlated with body mass index ( P = 0.02 and P < 0.001 , respectively ) , waist/hip ratio ( P = 0.05 and P = 0.01 ) , and central fat ( P = 0.03 and P = 0.003 ) . Specific insulin and insulin sensitivity ( IS ) , calculated by homeostatic model of assessment , were related to total fat ( P < 0.001 and P = 0.02 ) . GH treatment for 6 months led to a reduction in total fat ( P < 0.02 ) , percent fat ( P = 0.002 ) , central fat ( P = 0.012 ) , waist/hip ratio ( P < 0.05 ) , total cholesterol ( P = 0.03 ) , and apolipoprotein-B ( P = 00001 ) , as well as a decrease in the IS from 36.9 % ( range , 12 - 100 % ) to 25 % ( range , 2.5 - 55 % ; P = 0.0002 ) . This was paralleled by a rise in fasting ( total ) and specific insulin ( P = 0.016 and P = 0.002 ) . The degree of correlation among indices of IS , body composition , and fat distribution increased after GH treatment . Fasting plasma glucose rose significantly , but was within the reference range . During 12 months of GH therapy , a significant increase in serum lipoprotein-(a ) was observed ( P < 0.05 ) . Although GH has beneficial effects on central adiposity and lipid fractions , it is also associated with a decrease in IS ; these effects may vary between individuals Patients with type 2 diabetes on dialysis are at a substantially increased risk of cardiovascular and cerebrovascular diseases . Dyslipidemia characterized by moderately elevated low-density lipoprotein cholesterol and high triglycerides and low high-density lipoprotein cholesterol levels is common in this population . We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors would reduce vascular morbidity and mortality in this patient group . The ‘ Deutsche Diabetes Dialyse Studie ’ ( 4D study ) is a prospect i ve , r and omized , double-blind study involving 178 dialysis centers throughout Germany . Between March 1998 and October 2002 , 1,255 patients were r and omized to either atorvastatin 20 mg or placebo ; 677 men and 578 women , aged 30–83 years , have been enrolled . The study will be terminated as soon as the predefined number of 424 patients with primary combined end points ( i.e. , cardiovascular death , nonfatal myocardial infa rct ion , or fatal/nonfatal stroke ) will have occurred . The total cohort had the following characteristics at baseline : the mean age was 65.7 years , 54 % were men , 89 % had a history of hypertension , 21 % had coronary artery disease , 17.8 % had a history of stroke or a transient ischemic attack , and 45 % suffered from peripheral arterial disease . The mean time interval between the diagnosis of diabetes and the onset of dialysis was 17.4 years . On average , the patients were on hemodialysis for 8.3 months . Mean lipid and lipoprotein levels were : total cholesterol 219 ± 43 mg/dl , low-density lipoprotein cholesterol 126 ± 30 mg/dl , high-density lipoprotein cholesterol 36 ± 13 mg/dl , and triglycerides 264 ± 167 mg/dl . The results of the study will provide important information on the efficacy and safety of atorvastatin to support its use in patients with an impaired renal function who are at a high risk of vascular morbidity and mortality Objective To determine the effects of oral and transdermal hormone replacement therapy on lipid profile and hemostatic factors in postmenopausal women . Design Twenty subjects were treated with oral E2 valerate ( 2 mg ) combined with cyproterone acetate ( 1 mg ) ( group I ) and 21 with transdermal E2 ( 1.5 mg ) plus oral medroxyprogesterone acetate ( 5 mg ) ( group II ) . The effects on lipid profile and hemostatic parameters were evaluated at baseline and after 3 , 6 , and 12 months of treatment . Results Group I showed a stronger increase of high-density lipoprotein ( HDL ) cholesterol levels ( 2–8 % ) and stronger reduction of atherogenic indices ( total cholesterol/HDL cholesterol and low-density lipoprotein/HDL cholesterol ) than group II . Group II showed a more pronounced reduction of triglyceride ( 21–31 % ) and factor VII ( 6–10 % ) levels than group I. Both groups showed reduced concentrations of total cholesterol , low-density lipoprotein cholesterol , tissue plasminogen activator , plasminogen activator inhibitor-1 , antithrombin III , and protein S , whereas protein C was increased after 12 months of treatment . Conclusions The cardioprotective effects of hormone replacement therapy are demonstrated by favorable effects on lipid profile and fibrinolytic activity . Oral hormone replacement therapy showed a more prominent effect on lipoprotein metabolism than did transdermal administration , but transdermal medication had a stronger effect on triglyceride and coagulation factors . However , it needs to be considered that there is an increased risk of venous thrombotic events in the first year of treatment
Emerging cardiovascular risk factors/markers such as proinflammatory cytokines , C-reactive protein , and adipokines are also increased in GHD patients .
Increased cardiovascular morbidity and mortality have also been reported in GHD .
GH treatment has been shown to improve both traditional and emerging cardiovascular risk factors and markers .
The GHD population may be considered at high cardiovascular risk , and GH substitution may be expected to bring an added value to patients with hypopituitarism in terms of cardiovascular protection .
CONTEXT GH deficiency ( GHD ) of the adult is a clinical condition characterized by the presence of several traditional and emerging cardiovascular risk factors that can significantly increase cardiovascular morbidity and mortality .
It is still an open issue whether GH replacement is able not only to improve cardiovascular risk factors but also to decrease cardiovascular morbidity and mortality .
EVIDENCE SYNTHESIS In untreated GHD , cardiovascular risk is increased due to abnormal lipid profile ( increased total and low-density lipoprotein cholesterol , increased triglycerides , and reduced high-density lipoprotein cholesterol ) and impaired glucose metabolism .