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At least 775 records · Page 43Linked to original sources
PubMed1999

Lack of effect of simvastatin on insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia: results from a double-blind, randomized, placebo-controlled crossover study.

AIMS: To evaluate the effects of simvastatin on serum lipids and insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia. METHODS: A double-blind, randomized, placebo-controlled and two-period crossover study. After a 2-month run-in, 19 eligible Type 2 diabetic patients with hypercholesterolaemia were randomized to receive either simvastatin or placebo for 3 months, exchanging their treatment thereafter for another 3 months. Blood samples were taken in month 0 and at monthly intervals to measure serum lipids and indices of glycaemic control. An euglycaemic insulin clamp was performed in months 0, 3 and 6 to assess change of insulin sensitivity. The amount of glucose infused during 90-120 min of the clamp (M), and the mean values of serum insulin during 90-120 min (I) were measured. The M and M/I ratio were used to represent the in vivo insulin sensitivity of the subject. RESULTS: Simvastatin significantly reduced serum total cholesterol (TC) by 23+/-18% and low density lipoprotein-cholesterol (LDL-C) by 30+/-26%. It did not alter glycaemic control. The M-values and M/I ratios were similar in both groups in each period and no drug effect on insulin sensitivity could be identified. CONCLUSIONS: Simvastatin significantly reduced the serum TC and LDL-C levels without alteration of insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia.

Adult↗
PubMed2001

Risk factors for a major coronary event after myocardial infarction in the Scandinavian Simvastatin Survival Study (4S). Impact of predicted risk on the benefit of cholesterol-lowering treatment.

AIMS: To analyse (1) the prognostic importance of clinical findings and lipids in patients with a previous myocardial infarction and (2) the relative and absolute benefit of simvastatin in patients at low, medium and high predicted risk. METHODS: The 4S was a double-blind, randomized, clinical trial of long-term treatment with simvastatin or matching placebo in patients with myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol x l(-1), and serum triglycerides <or=2.5 mmol x l(-1). The present study only deals with those 3525 patients who had a previous myocardial infarction. End-points comprised coronary death, definite and probable hospital verified myocardial infarction, and resuscitated cardiac arrest. Because there were few women the primary analyses were performed among men. RESULTS: A Cox model analysis in the placebo group identified the following independent predictors of coronary events: a history of hypertension (P=0.023), diabetes (P=0.0001), smoking after the myocardial infarction (P=0.010), total cholesterol (P=0.020), and HDL cholesterol (P=0.062). The relative reduction of risk by simvastatin treatment in patients at low, medium and high predicted risk was 38%, 39% and 42%, respectively, but the corresponding absolute benefit per 100 patients treated for 6 years increased from 7.9 to 16.2. CONCLUSION: In addition to serum lipids, clinical variables contributed significantly to prediction. The relative benefit from simvastatin treatment was independent of predicted risk, but the absolute benefit increased from low to high risk.

Anticholesteremic Agents↗
PubMed2004

Bioequivalence study of two formulations of simvastatin tablets in healthy Thai volunteers.

The bioequivalence of two formulations of 10 mg tablets of simvastatin (CAS 79902-63-9), Vascor as test and a commercially available preparation as reference, in 18 healthy Thai male volunteers was assessed. In a randomized, single dose, two-period, crossover study design with a 1-week wash-out period, each subject received 4 tablets of 10-mg simvastatin tablets. Plasma samples were collected over a 24-h period after administration. Subsequently, plasma concentrations of simvastatin and its hydroxy acid metabolite were analyzed by using LC/ MS/MS. Pharmacokinetic parameters were determined by using non-compartmental analysis. The results showed that 90% confidence intervals of the peak concentration (Cmax) and the area under the concentration-time curve (AUC) of simvastatin and its hydroxy acid metabolite of reference and test were within 80 %-125%. Consequently the bioequivalence of these two preparations can be concluded.

Adolescent↗
PubMed2000

Simvastatin, capillary permeability, and acetylcholine-mediated vasomotion in atherosclerotic, hypercholesterolemic men.

OBJECTIVES: The aim of this study was to test the effect of high-dose simvastatin therapy on vascular permeability, a key variable in the atherogenic process, and endothelial-mediated vasodilator responses in patients with hypercholesterolemic atherosclerosis. METHODS: The transcapillary albumin escape rate (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of macromolecular permeability of capillary endothelium) and forearm vasodilatation (venous plethysmography) to intraarterial acetylcholine and sodium nitroprusside (7.5, 15, 30 microg/min and 0.8, 1.6, and 3.2 microg/min respectively, 5 minutes at each rate) to account for endothelium-dependent and independent mechanisms, were measured at baseline and after 1-month simvastatin (40 mg once daily) in 16 hypercholesterolemic (low-density lipoprotein cholesterol >130 mg/dL), atherosclerotic men. Thirteen healthy, untreated subjects were the controls. RESULTS: Baseline TERalb was higher and responsiveness to both acetylcholine and sodium nitroprusside was depressed in patients compared with controls. One-month high-dose simvastatin reduced low-density lipoprotein cholesterol by 39%, normalized TERalb, and improved local vasomotor responses to acetylcholine, without modifying those to sodium nitroprusside. Changes in TERalb and acetylcholine-mediated vasodilatation were dissociated and unrelated to lipid modifications. CONCLUSIONS: Low-density lipoprotein cholesterol reduction through 1 month of high-dose simvastatin normalized the exaggerated transvascular albumin leakage of patients with hypercholesterolemic atherosclerosis, perhaps by restoring an exaggerated endothelial permeability, apparently through mechanisms independent of circulating lipids. Improvements in acetylcholine-mediated vasomotion were also evident, but were dissociated from TERalb, demonstrating a heterogeneous behavior of the 2 indices of endothelial function in response to high-dose statin treatment.

Acetylcholine↗
PubMed2002

Simvastatin-induced lactic acidosis: a rare adverse reaction?

Simvastatin, a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used cholesterol-lowering agent. The long-term safety profile of simvastatin, established over 10 years of clinical use, is excellent. HMG-CoA reductase inhibitors block 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis. However, other important nonsterol compounds, such as coenzyme Q10 (CoQ10), are also derived from the same synthetic pathway. CoQ10 is an essential carrier in the mitochondrial respiratory chain that participates in oxidative phosphorylation. Simvastatin and other HMG-CoA reductase inhibitors have been documented to lower serum concentrations of CoQ10. It has been suggested that the adverse effect of myopathy caused by HMG-CoA reductase inhibitors is due to CoQ10 deficiency in the tissue mitochondria. Documentation of this cause-and-effect phenomenon, however, has been lacking. We offer evidence that lactic acidosis may develop as a complication of simvastatin therapy. Our patient also manifested the well-known HMG-CoA reductase inhibitor drug toxicities of rhabdomyolysis and hepatitis. The occurrence of these known adverse events with lactic acidosis in our patient suggests that interference of the mitochondrial respiratory chain may play a role in the toxicity of this class of drugs.

Acidosis, Lactic↗
PubMed2001

Simvastatin effects on a human lung carcinoma and cholesterol homeostasis of host and non-host mice.

In order to investigate the effect of a competitive inhibitor of the HMG-CoA reductase on tumor growth and cholesterol homeostasis of host and non-host mice, we maintained a human lung mucoepidermoid carcinoma (HLMC) in nude mice, treating these animals with Simvastatin for 33 days. The drug increased the total activity of hepatic HMG-CoA reductase without affecting the cholesterolemia. Non-treated host animals presented lower serum, tissue and microsomal hepatic cholesterol than non-host animals. These differences disappeared when animals were treated with Simvastatin, though the induction of the reductase activity at mid-dark was higher in non-host than in host animals. Simvastatin produced no significant effects on both final tumor volume and body weight. Synthesis and cholesterol homeostasis restoration induced by liver and tumoral reductase would account for no effect on the HLMC growth after a long treatment with Simvastatin.

Animals↗
PubMed1999

Rationale, design, and baseline results of the Pravastatin-to-Simvastatin Conversion Lipid Optimization Program (PSCOP).

A program designed to increase the percentage of patients at a Department of Veterans Affairs health system who meet their cholesterol goals as recommended by the National Cholesterol Education Program (NCEP) is described, and baseline results are reported. Patients with an active prescription for pravastatin between February 4 and June 4, 1997, were identified for conversion to simvastatin by means of the Pravastatin-to-Simvastatin Conversion Lipid-Optimization Program; 1361 patients were eligible for conversion. Each patient was mailed a survey for determining risk factors for coronary heart disease (CHD) and NCEP-recommended low-density lipoprotein (LDL) cholesterol goal and was asked to provide a fasting blood sample for determination of lipid profile, liver function, and serum creatine phosphokinase concentration. The patients were asked to make a follow-up laboratory visit six to seven weeks after they had started taking simvastatin. The percentage change from baseline and the percentage of patients who meet their LDL cholesterol goal before and after the conversion will be determined. A total of 1115 patients were converted to simvastatin. Only 35.4% of patients taking pravastatin to prevent a second CHD-related event met or exceeded their LDL cholesterol goal. Only 36.2% of patients with two or more CHD risk factors who were taking pravastatin for primary prevention met or exceeded their LDL cholesterol goal. In a veterans population, less than half of patients receiving a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor had LDL cholesterol concentrations that met goals recommended by the NCEP.

Aged↗
PubMed1988

Effects of simvastatin on plasma lipid, lipoprotein and apolipoprotein concentrations in hypercholesterolaemia.

The effect of 24 weeks of treatment with simvastatin, a new HMG coenzyme A reductase inhibitor (dosages of 20 and 40 mg day-1) on serum lipid, lipoprotein and apolipoprotein A-I and B concentrations as well as safety parameters and subjective side effects were studied in 11 patients with familial (FH) and 10 patients with polygenic hypercholesterolaemia (P-HC). The effects on plasma lipoprotein and apolipoprotein concentrations had already been achieved after four weeks in both groups and then remained during the study. In FH, mean fasting plasma total cholesterol concentration decreased from 10.51 to 6.71 mmol l-1 (36%), and in P-HC from 6.55 to 4.54 mmol l-1 (31%) at 24 weeks (P less than 0.001). Mean plasma low density lipoprotein (LDL) cholesterol concentrations also decreased, in FH from 8.87 to 5.05 mmol l-1 (43%) and in P-HC from 4.97 to 3.12 mmol l-1 (37%) at 24 weeks (P less than 0.001). Furthermore, apolipoprotein B concentrations decreased significantly from 2.21 to 1.57 g l-1 (29%) (less than 0.001) in FH and from 1.53 to 1.09 g l-1 (29%) (P less than 0.01) in P-HC. Plasma high density lipoprotein (HDL) cholesterol increased in both FH and P-HC during treatment. Increases were seen in both the subfractions HDL2 and HDL3. Simvastatin was well tolerated. No serious clinical or laboratory adverse effects were observed. It is concluded that 24 weeks of treatment with simvastatin in doses up to 40 mg day-1 effectively reduces plasma total and LDL cholesterol concentrations without causing subjective or significant objective side effects. Thus, simvastatin may be of great interest in future studies for prevention of coronary heart disease due to hypercholesterolaemia.

Adult↗
PubMed2005

Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels.

Increased matrix metalloproteinase-9 (MMP-9) expression is associated with intimal hyperplasia in saphenous vein (SV) bypass grafts. Recent evidence suggests that HMG-CoA reductase inhibitors (statins) can prevent the progression of vein graft failure. Here we investigated whether statins inhibited MMP-9 secretion from cultured human SV smooth muscle cells (SMC) and examined the underlying mechanisms. SV-SMC from different patients were exposed to phorbol ester (TPA) or PDGF-BB plus interleukin-1alpha (IL-1). MMP-9 secretion and mRNA expression were analyzed using gelatin zymography and RT-PCR, respectively. Specific signal transduction pathways were investigated by immunoblotting and pharmacological inhibition. Simvastatin reduced TPA- and PDGF/IL-1-induced MMP-9 secretion and mRNA levels, effects reversed by geranylgeranyl pyrophosphate and mimicked by inhibiting Rho geranylgeranylation or Rho-kinase (ROCK). MMP-9 secretion induced by PDGF/IL-1 was mediated via the ERK, p38 MAPK, and NFkappaB pathways, whereas that induced by TPA was mediated specifically via the ERK pathway. Simvastatin failed to inhibit activation of these signaling pathways. Moreover, simvastatin did not affect MMP-9 mRNA stability. Together these data suggest that simvastatin reduces MMP-9 secretion from human SV-SMC by inhibiting the RhoA/ROCK pathway and decreasing MMP-9 mRNA levels independently of effects on signaling pathways required for MMP-9 gene expression.

Alkyl and Aryl Transferases↗
PubMed2003

Simvastatin attenuates renal ischemia/reperfusion injury in rats administered cyclosporine A.

BACKGROUND: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors increase renal blood flow independent of their lipid-lowering properties. In organ transplantation, the calcineurin inhibitor cyclosporine A (CyA) is the immunosuppressant of choice. However, its renal vasoconstrictor properties limit its use. This study aimed to determine the effect of an HMG-CoA reductase inhibitor, simvastatin (Zocor), on renal function in rats after ischemia/reperfusion injury (I/R) with concomitant CyA treatment. METHODS: Male Wistar rats (250 g) were anesthetized and the suprarenal aorta clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into 5 groups: (1) control rats, no ischemia, no treatment; (2) ischemia with no treatment; (3) ischemia plus CyA only; (4) ischemia plus CyA and low-dose simvastatin; and (5) ischemia plus CyA and high-dose simvastatin. Five to 7 days after I/R injury, glomerular filtration rate (GFR) was determined using urinary iohexol clearance. RESULTS: The GFR values (mL/min) for all 5 groups were as follows: (1) 1.23 +/- 0.08; (2) 1.05 +/- 0.10; (3) 0.44 +/- 0.06 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); (4) 0.51 +/- 0.04 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); and (5) 0.85 +/- 0.11. CONCLUSIONS: After I/R injury and cyclosporine treatment, simvastatin preserved renal function compared with cyclosporine treatment alone because it may not have a direct vasoconstrictor effect on the renal microcirculation. In fact, it may exhibit vasodilator properties on the renal microcirculation mediated by nitric oxide.

Analysis of Variance↗
PubMed2004

Increased soluble CD40L levels are reduced by long-term simvastatin treatment in peritoneally dialyzed patients.

BACKGROUND: Dyslipidemia and increased mortality due to cardiovascular events are common in peritoneally dialyzed patients [continuous ambulatory peritoneal dialysis (CAPD)]. Statins show beneficial effects on serum lipids and reduce cardiovascular mortality. The CD40-CD40 ligand (CD40L) system has proved critical for the activation of tissue structural cells that include endothelial cells, epithelial cells and fibroblasts. It has been reported that enhanced CD40L-CD40 interaction in familial hypercholesterolemia may be downregulated by statins, but prospective studies on CAPD patients are lacking. AIM: To determine the effects of 6 months treatment with simvastatin on platelet aggregation, markers of endothelial cell injury, and sCD40L in 15 hyperlipidemic CAPD patients. METHODS: Simvastatin (Zocor, Merck Sharp & Dohme) was given in a dose of 10 mg at bedtime. RESULTS: CD40L decreased significantly after 6 months of the therapy. Thrombomodulin decreased significantly after 3 months of the therapy, whereas von Willebrand factor, E-selectin and P-selectin did not change significantly during the study. CONCLUSION: Simvastatin reduced enhanced sCD40L levels together with amelioration of endothelial dysfunction. Treatment with simvastatin might downregulate enhanced CD40L-CD40 interactions in CAPD patients.

Arteriosclerosis↗
PubMed1990

Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension.

Mortality from coronary artery disease is a common problem in treated hypertensive patients, and these people have a high prevalence of elevated cholesterol levels. A study was undertaken to determine whether cholesterol could be lowered effectively without major side effects in patients with treated hypertension. Forty-nine patients (mean age 67.6 years) with cholesterol greater than 5.5 mmol/l were placed on a reduced-fat (less than 30% of calories from fat with a ratio of polyunsaturated to saturated fats of less than 1) diet for 3 months. If the cholesterol was between 5.5 and 7.5 mmol/l and total cholesterol divided by high-density lipoprotein cholesterol was greater than 4.5, the patients were randomly allocated either to the simvastatin (24 patients) or the placebo group (25 patients). Diet and placebo caused minor and insignificant falls in cholesterol and no change in triglycerides or lipids. Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01). Total cholesterol divided by high-density lipoprotein cholesterol fell from 6.3 to 4.0 (P less than 0.001). The drug was well tolerated and the side-effect profile did not differ from the placebo in clinical or biochemical events. The active drug was stopped in one patient (abdominal pain, dizziness, headache, tiredness) and in two patients taking the placebo (elevated creatine phosphokinase, cardiovascular collapse). Simvastatin effectively lowered total cholesterol and improved the lipoprotein profile. The dose required in most patients was 40 mg/day. Simvastatin may be an acceptable drug to improve the lipoprotein profile in order to determine whether this improves the prognosis in patients treated for hypertension.

Adult↗
PubMed2006

Synergistic antimyeloma effects of zoledronate and simvastatin.

Despite advances in the treatment of multiple myeloma, it remains an incurable disease because of primary and secondary drug resistance. Mevalonate pathway inhibitors like bisphosphonates and statins have antimyeloma activity in vitro at very high concentrations, which may probably not be reached in vivo. NCI-H929, OPM-2, U266 and RPMI-8226 myeloma cell lines were treated in the presence or absence of bone marrow stromal cells with simvastatin or zoledronate in combination with classical antimyeloma drugs like melphalan or bortezomib. Zoledronate did not show substantial antimyeloma activity at low and intermediate concentrations, whereas simvastatin potently induced apoptosis in myeloma cells without signs of primary, cell-adhesion-mediated drug resistance. Furthermore, sequential blockage of the mevalonate pathway by zoledronate and simvastatin demonstrated synergistic induction of apoptosis and reversal of cell-adhesion-mediated drug resistance. Our data provide a rationale for combining zoledronate and simvastatin with classical antimyeloma drugs.

Apoptosis↗
PubMed2004

Simvastatin acutely reduces myocardial reperfusion injury in vivo by activating the phosphatidylinositide 3-kinase/Akt pathway.

Long-term pretreatment with statins reduces myocardial injury after acute ischemia and reperfusion by increasing the expression of endothelial nitric oxide synthase (eNOS). We hypothesized that statins may act rapidly enough to protect the myocardium from ischemia/reperfusion injury when given right at the beginning of the reperfusion period and tried to delineate the role of PI 3-kinase/Akt pathway in early eNOS activation. Activated simvastatin was given intravenously 3 minutes before starting the reperfusion after temporary coronary artery occlusion (CAO) in anaesthetized rats. Simvastatin significantly increased myocardial PI 3-kinase activity, AktSer473, and eNOSSer1177 phosphorylation and reduced infarct size by 42%. Infarct size reduction as well as activation of PI 3-kinase/Akt/eNOS pathway were not observed in rats co-treated with the PI 3-kinase inhibitor wortmannin. Contribution of eNOS was further delineated using the NOS inhibitor L-NAME, which could completely block cardioprotection by the statin. In summary, simvastatin acutely reduces the extent of myocardial necrosis in normocholesterolemic rats in an NO- dependent manner by activating the PI 3-kinase/Akt pathway. This is the first study demonstrating short-term cardioprotective effects of simvastatin in an in vivo model of ischemia/reperfusion.

Androstadienes↗
PubMed2003

Rhabdomyolysis associated with simvastatin-nefazodone therapy.

Simvastatin is a hydroxymethyl glutaryl coenzyme A reductase inhibitor commonly used to treat patients with hyperlipidemia. It is a safe and effective medication in most patients when used appropriately. A serious side effect known as rhabdomyolysis may rarely occur in patients who take simvastatin, especially at higher doses and with agents that interact and increase the level of simvastatin in the blood. We describe the case of a patient with rhabdomyolysis that occurred after the patient's simvastatin was titrated to 80 mg at approximately the same time that his antidepressant medication was switched to nefazodone. We found only two other similar cases in the literature, both of which were presented as letters to the editor in two different journals. We present this case to add to the literature and to assist practitioners by raising their awareness of this interaction so that it can be monitored.

Antidepressive Agents, Second-Generation↗
PubMed1991

Effect of simvastatin and fenofibrate on the fatty acid composition of hypercholesterolaemic patients.

1. The effects of simvastatin (one of a new class of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) and fenofibrate on the fatty acid composition of cholesterol esters, phospholipids and triglycerides of different lipoproteins of 15 patients with primary hypercholesterolaemia were compared in a double-blind study. 2. Fenofibrate (300 mg day-1) increased the relative content of saturated fatty acids of cholesterol esters, phospholipids and triglycerides in VLDL, IDL and HDL. It also increased the relative content of monounsaturated fatty acids of cholesterol esters and phospholipids in all fractions and those of triglycerides in VLDL and IDL. In contrast, it decreased the proportion of polyunsaturated fatty acids of cholesterol esters and phospholipids in all fractions and those of triglycerides in VLDL and IDL. The polyunsaturated/saturated (P/S) ratio was reduced in cholesterol esters and phospholipids in VLDL and in phospholipids in IDL by fenofibrate. The drug significantly increased the 18:1w9/18:2w6 ratio in cholesterol esters and phospholipids in VLDL, LDL and HDL, but produced a non-significant increase in the ratio in IDL. 3. Simvastatin (20 mg day-1) produced a significant decrease in saturated fatty acid and an increase in polyunsaturated fatty acid in triglycerides in VLDL. Simvastatin, in contrast to fenofibrate caused a slight decrease in saturated and monounsaturated fatty acids in the three other lipoprotein fractions, and an increase in polyunsaturated fatty acids. The P/S and 18:1w9/18:2w6 ratios were not modified by simvastatin.

Adult↗
PubMed1994

Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers.

1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4-6 week washout phase. 3. CNS measures included EEG evoked potentials, power spectral analysis, Leeds Sleep Questionnaire, Hospital Anxiety Depression (HAD) Scale, and Digit Symbol Substitution Test (DSST); biochemical measures included plasma cholesterol, liver enzymes (gamma-GT, AST, ALT) and creatine kinase. 4. Mean cholesterol concentrations with both drugs were significantly lower than with placebo, and the cholesterol-lowering effect was greater with simvastatin. There were no significant differences between treatment in EEG evoked potentials, HAD Scale, or DSST scores. On the sleep measure, subjects reported significantly greater difficulty in getting to sleep while on simvastatin than on pravastatin, but neither score differed from placebo. No significant correlations were observed between sleep ratings and either plasma cholesterol concentrations or EEG evoked potentials. 5. The study showed that, while both drugs reduced plasma cholesterol concentrations, neither exerted significant effects, compared with placebo, on EEG evoked potentials, mood, sleep, or cognitive performance after 4 weeks of chronic administration in healthy volunteers.

Adult↗
PubMed1989

Effects of inhibition of cholesterol synthesis by simvastatin on the production of adrenocortical steroid hormones and ACTH.

Simvastatin, a derivative of lovastatin, is a potent inhibitor of cholesterol biosynthesis and may interfere with steroid hormone production, for which cholesterol is required. In a single-blind, placebo-controlled study, 24 patients with severe primary hypercholesterolaemia (mean serum cholesterol +/- SD = 10.74 +/- 1.59 mmol/l) were treated with simvastatin 40 mg per day for 8 weeks. Before and after treatment, the following parameters were evaluated: basal levels of ACTH, cortisol, androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone; urinary excretion of free cortisol; the cortisol response after short-term infusion of ACTH; the ACTH and cortisol response during insulin-induced hypoglycaemia. Total serum cholesterol decreased by 35.0 +/- 8.1% (P less than 0.001) and low-density lipoprotein (LDL) cholesterol by 39.8 +/- 9.8% (P less than 0.001); high-density lipoprotein (HDL) increased by 9.2 +/- 11.1% (P less than 0.001). Basal levels of ACTH were higher after simvastatin (2.9 +/- 1.9 pmol/l vs 4.1 +/- 2.9 pmol/l; P less than 0.05) whereas basal levels of steroid hormones were not significantly changed. The excretion of free cortisol was unaltered. The peak cortisol after ACTH infusion was lower after treatment (0.87 +/- 0.23 mumol/l vs 0.78 +/- 0.10 mumol/l; P less than 0.05), but was unaltered during insulin-induced hypoglycaemia. We conclude that simvastatin lowers serum cholesterol without clinically relevant effects on the adrenocortical steroid hormone secretion and the hypothalamic-pituitary-adrenal axis.

Adrenal Cortex Hormones↗