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Meta-Analysis
. 2021 Jan 22;1(1):CD013211.
doi: 10.1002/14651858.CD013211.pub2.

Effect of atorvastatin on testosterone levels

Muhammad Ismail Shawish  1 , Bahador Bagheri  2   3 , Vijaya M Musini  1 , Stephen P Adams  1 , James M Wright  1
Affiliations
Meta-Analysis

Effect of atorvastatin on testosterone levels

Muhammad Ismail Shawish et al. Cochrane Database Syst Rev. .

Abstract

Background: Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial.

Objectives: Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment.

Search methods: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work.

Selection criteria: RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females.

Data collection and analysis: Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence.

Main results: We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 μmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels.

Authors' conclusions: We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.

PubMed Disclaimer

Conflict of interest statement

Muhammad Ismail Shawish: nothing to declare.

Bahador Bagheri: nothing to declare.

Vijaya Musini: nothing to declare.

Stephen Adams: nothing to declare.

James Wright: nothing to declare.

Figures

1
1
PRISMA diagram for screening studies
2
2
Risk of bias summary of the included studies
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
4
4
Forest plot of comparison: Atorvastatin versus control (fixed‐effect model), outcome: Total testosterone in males.
5
5
Forest plot of comparison: 5 Atorvastatin versus control (fixed‐effect model), outcome: 5.7 Withdrawal due to adverse effects (WDAEs).
6
6
1.1
1.1. Analysis
Comparison 1: Atorvastatin versus control (fixed‐effect model), Outcome 1: Total testosterone in males
1.2
1.2. Analysis
Comparison 1: Atorvastatin versus control (fixed‐effect model), Outcome 2: Total testosterone in females
1.3
1.3. Analysis
Comparison 1: Atorvastatin versus control (fixed‐effect model), Outcome 3: Sex hormone binding globulin (SHBG)
1.4
1.4. Analysis
Comparison 1: Atorvastatin versus control (fixed‐effect model), Outcome 4: Androstenedione
1.5
1.5. Analysis
Comparison 1: Atorvastatin versus control (fixed‐effect model), Outcome 5: Dehydroepiandrosterone sulfate (DHEAS)
1.6
1.6. Analysis
Comparison 1: Atorvastatin versus control (fixed‐effect model), Outcome 6: Withdrawal due to adverse effects (WDAEs)
1.7
1.7. Analysis
Comparison 1: Atorvastatin versus control (fixed‐effect model), Outcome 7: Free androgen index (FAI)
2.1
2.1. Analysis
Comparison 2: Atorvastatin vs control (random effects model), Outcome 1: Total testosterone in females
2.2
2.2. Analysis
Comparison 2: Atorvastatin vs control (random effects model), Outcome 2: Androstenedione
2.3
2.3. Analysis
Comparison 2: Atorvastatin vs control (random effects model), Outcome 3: Free androgen index (FAI)
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    1. Inukai K, Iuchi T, Sumita T, Ito D, Ikebukuro K, Imai K, et al. [Combination therapy with angiotensin receptor blocker (ARB) plus atorvastatin reduced proteinuria in type 2 diabetic patients with diabetic nephropathy]. Therapeutic Research 2011;32(7):947-53. [EMBASE: 2011473820]
IRCT201208299626N1 {published data only}
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Ishola 2017 {published data only}
    1. Ishola IO, Tijani HK, Dosumu OO, Anunobi CC, Oshodi TO. Atorvastatin attenuates testosterone-induced benign prostatic hyperplasia in rats: role of peroxisome proliferator-activated receptor-gamma and cyclo-oxygenase-2. Fundamental & Clinical Pharmacology 2017;31(6):652-62. - PubMed
Issa 2012 {published data only}
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Jayaram 2007 {published data only}
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Joy 2008 {published data only}
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Kadoglou 2011 {published data only}
    1. Kadoglou NPE, Vrabas IS, Kapelouzou A, Lampropoulos S, Sailer N, Kostakis A, et al. Impact of atorvastatin on serum vaspin levels in hypercholesterolemic patients with moderate cardiovascular risk. Regulatory Peptides 2011;170(1-3):57-61. - PubMed
Kajimoto 2009 {published data only}
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Kappelle 2009 {published data only}
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Kappelle 2010 {published data only}
    1. Kappelle PJ, Dallinga-Thie GM, Dullaart RP, Diabetes Atorvastatin Lipid Intervention (DALI) study group. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets. Biochimica et Biophysica Acta 2010;1801(1):89-94. [MEDLINE: ] - PubMed
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Knopp 2006 {published data only}
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Koh 2010 {published data only}
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Konduracka 2008 {published data only}
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Krysiak 2010 {published data only}
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Krysiak 2014 {published data only}
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Krysiak 2016 {published data only}
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Kuznetsova 2010 {published data only}
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Lamon‐Fava 2007 {published data only}
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Lins 2004 {published data only}
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Liu 2009 {published data only}
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Loughrey 2013 {published data only}
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Macchia 2012 {published data only}
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Macin 2005 {published data only}
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Magen 2004 {published data only}
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Malekzadeh 2010 {published data only}
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Manuel 2003 {published data only}
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Martin 2011 {published data only}
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Martin‐Ventura 2005 {published data only}
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Mishra 2005 {published data only}
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Mohler 2003 {published data only}
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Naoumova 2003 {published data only}
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NCT00433823 {published data only}
    1. NCT00433823. A Study Evaluating the Effects of Lipid Lowering Treatment on Steroid Synthesis. https://clinicaltrials.gov/show/nct00433823.
NCT00522158 {published data only}
    1. NCT00522158. Effects of Achieving Very Low LDL-Cholesterol After Treatment With Statins on Steroidogenesis and Cognition. https://clinicaltrials.gov/show/nct00522158.
NCT00603590 {published data only}
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NCT01555632 {published data only}
    1. NCT01555632. Atorvastatin Calcium in Preventing Metabolic Syndrome in Patients With Prostate Cancer Receiving Long-Term Androgen-Deprivation Therapy. https://clinicaltrials.gov/show/nct01555632.
NCT02497638 {published data only}
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NCT03784703 {published data only}
    1. NCT03784703. Type 2 Diabetic Patients Maintained on Statin Therapy. Https://clinicaltrials.gov/show/nct03784703 2018;(PG -).
NCT04101136 {published data only}
    1. NCT04101136. Effect of Atorvastatin on Subclinical Atherosclerosis. https://clinicaltrials.gov/show/NCT04101136 2019;(PG -).
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Ozkiris 2007 {published data only}
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Panahi 2011 {published data only}
    1. Panahi Y, Pishgoo B, Beiraghdar F, Araghi Z M, Sahebkar A, Abolhasani E. Results of a randomized,open-label,clinical trial investigating the effects of supplementation with Heracleumpersicum extract as an adjunctive therapy for dyslipidemia. Thescientificworldjournal 2011;11:592-601. - PMC - PubMed
Paolisso 2000 {published data only}
    1. Paolisso G, Barbagallo M, Petrella G, Ragno E, Barbieri M, Giordano M, et al. Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependent diabetic patients. Atherosclerosis 2000;150(1):121-7. - PubMed
Papathanasiou 2008 {published data only}
    1. Papathanasiou AI, Lourida ES, Tsironis LD, Goudevenos JA, Tselepis AD. Short- and long-term elevation of autoantibody titers against oxidized LDL in patients with acute coronary syndromes. Role of the lipoprotein-associated phospholipase A2 and the effect of atorvastatin treatment. Atherosclerosis 2008;196(1):289-97. - PubMed
Parini 2008 {published data only}
    1. Parini P, Gustafsson U, Davis MA, Larsson L, Einarsson C, Wilson M, et al. Cholesterol synthesis inhibition elicits an integrated molecular response in human livers including decreased ACAT2. Arteriosclerosis, Thrombosis, & Vascular Biology 2008;28(6):1200-6. [MEDLINE: ] - PMC - PubMed
Parker 2011 {published data only}
    1. Parker BA, Capizzi JA, Augeri AL, Grimaldi AS, Michael White C, Thompson PD. Atorvastatin increases exercise leg blood flow in healthy adults. Atherosclerosis 2011;219(2):768-73. - PMC - PubMed
Parker 2013 {published data only}
    1. Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, et al. Effect of statins on skeletal muscle function. Circulation 2013;127(1):96-103. - PMC - PubMed
Pedro‐Botet 2001 {published data only}
    1. Pedro-Botet J, Schaefer EJ, Bakker-Arkema RG, Black DM, Stein EM, Corella D, et al. Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner. Atherosclerosis 2001;158(1):183-93. - PubMed
Peng 2018 {published data only}
    1. Peng Y, Ou BQ, Li HH, Liang FL. Atorvastatin and folic acid improve cardiac function and inhibit ventricular remodeling in chronic heart failure patients with hyperhomocysteinemia. Journal of the Hong Kong College of Cardiology 2018;26(1):32. - PMC - PubMed
Petri 2011 {published data only}
    1. Petri MA, Kiani AN, Post W, Christopher-Stine L, Magder LS. Lupus Atherosclerosis Prevention Study (LAPS). Annals of the Rheumatic Diseases 2011;70(5):760-5. - PubMed
Pfiser 2003 {published data only}
    1. Pfiser. The atorvastatin efficacy and safety study in diabetic patients to determine starting dose for effectively reducing lipids. (The ADSL study). Protocol No. A2581080 2003.
Pfizer 2003a {published data only}
    1. Pfizer Inc. A Multi-National, Prospective Randomized Double-Blind, Multi-Center, Placebo-Controlled Study To Evaluate Efficacy And Safety Of A Fixed Combination Therapy Of Amlodipine And Atorvastatin In The Treatment Of Concurrent Hypertension And Hyperlipidemia - Th. Protocol No. A3841003 2003.
Pfizer 2003b {published data only}
    1. Pfizer Inc. Double-blind, placebo-controlled, dose ranging trial to evaluate the efficacy of atorvastatin on bone mineral density and markers for bone turnover in postmenopausal women with dyslipidemia and at risk for osteoporosis. Protocol No. A2581049 2003.
Pfizer 2003c {published data only}
    1. Pfizer Inc. A Multicenter, Randomized, Double-Blind, Placebo-Controlled And Open-Label Evaluation Of The Safety And Efficacy Of Dual Therapy With Atorvastatin Plus Amlodipine When Compared To Either Therapy Alone In The Treatment Of Patients With Simultaneous Hyperlipidemia And Hypertension. (The Avalon Study). Protocol no. A3841001 2003.
Pfizer 2004a {published data only}
    1. Pfizer Inc. A 4-year, double-blind, randomized, placebo-controlled, study of atorvastatin as prevention of CHD endpoints in patients with (Type II) non-insulin dependent diabetes mellitus. (ASPEN). Protocol No. 0981-071 2004.
Pfizer 2004b {published data only}
    1. Pfizer Inc. Impact Of Atorvastatin On The Distribution, Composition And Metabolism Of LDL (Low Density Lipoprotein) And HDL (High Density Lipoprotein) Subfractions: A Double-Blind Placebo-Controlled Phase IV Study With Patients Suffering From Combined Hyperlipidemia And Diabetes - Atorvastatin And LDL Profile In NIDDM (ALPIN Study). https://www.clinicaltrials.gov/ct2/show/NCT00640549 2004.
Pfizer 2004c {published data only}
    1. Pfizer Inc. A multicenter, double blind, randomized, placebo controlled parallel group study to assess the efficacy and safety of atorvastatin in the treatment of men with lower urinary tract symptoms and urinary outflow obstruction associated with benign prostatic enlargement. Protocol No. A2581125 2004.
Pfizer 2005 {published data only}
    1. Pfizer Inc. Phase 2, multi-center, double-blind, placebo-controlled, randomized, parallel group, dose response study of the safety and efficacy of CP-529,414 combination with open-label atorvastatin once daily (QD) for 12 weeks in subjects with hypercholesterolemia and without overt cardiovascular disease. Pfizer 2005.
Pfizer 2006a {published data only}
    1. Pfizer Inc. A multi-center, randomized, open-label study to evaluate efficacy and safety of dual therapy with atorvastatin plus amlodipine when compared to amlodipine therapy alone in the treatment of subjects with concurrent hyperlipidemia and hypertension. Protocol No. A3841026 2006.
Pfizer 2006b {published data only}
    1. Pfizer Inc. A phase 3, double-blind, placebo-controlled, randomized, parallel group, multicenter study of the efficacy, safety and tolerability of fixed combination torcetrapib/atorvastatin administered orally, once daily for 6 months, compared to atorvastatin alone or placebo, in subjects with mixed dyslipidemia (Frederickson types IIa and IIb). Protocol No. A5091018 2006.
Pfizer 2007 {published data only}
    1. Pfizer Inc. Carotid Atorvastatin Study in Hyperlipidemic Post-MEnopausal Women: a Randomised Evaluation of Atorvastatin Versus Placebo (CASHMERE). Protocol A2581051. Http://pdf.clinicalstudyresults.org/documents/company-study_2902_0.pdf 2007:1-11.
Pfizer 2009 {published data only}
    1. Pfizer Inc. Atorvastatin and cardiovascular complications in Type II diabetes dialysis patients. The German Diabetes Dialysis Study: 4D Study. Determination of Cardiovascular endpoints in NIDDM dialysis patients. Protocol No. CT-981-423-239 2009.
Pfizer 2010 {published data only}
    1. Pfizer Inc. A double-blind, placebo-controlled study of atorvastatin as prevention of CHD in high risk patients with non-insulin-dependent diabetes mellitus(CARDS). Protocol No. 0981-430-102 2010.
Piperi 2004 {published data only}
    1. Piperi C, Kalofoutis C, Lagogianni I, Troupis G, Kalofoutis A. Comparison of raloxifene and atorvastatin effects on serum lipids composition of healthy post-menopausal women. Molecular & Cellular Biochemistry 2004;261(1):71-5. [MEDLINE: ] - PubMed
Plazak 2011 {published data only}
    1. Plazak W, Gryga K, Dziedzic H, Tomkiewicz-Pajak L, Konieczynska M, Podolec P, et al. Influence of atorvastatin on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients: a prospective, randomized, double-masked, placebo-controlled study. Arthritis Research & Therapy 2011;13(4):R117. - PMC - PubMed
Pons‐Rejraji 2014 {published data only}
    1. Pons-Rejraji H, Brugnon F, Sion B, Maqdasy S, Gouby G, Pereira B, et al. Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: A pilot prospective clinical trial. Reproductive Biology & Endocrinology 2014;12(1):12. [MEDLINE: ] - PMC - PubMed
Pontrelli 2002 {published data only}
    1. Pontrelli L, Parris W, Adeli K, Cheung R C. Atorvastatin treatment beneficially alters the lipoprotein profile and increases low-density lipoprotein particle diameter in patients with combined dyslipidemia and impaired fasting glucose/type 2 diabetes. Metabolism: Clinical & Experimental 2002;51(3):334-42. [MEDLINE: ] - PubMed
Preston 2007 {published data only}
    1. Preston RA, Harvey P, Herfert O, Dykstra G, Jukema J W, Sun F, et al. A randomized, placebo-controlled trial to evaluate the efficacy, safety, and pharmacodynamic interaction of coadministered amlodipine and atorvastatin in 1660 patients with concomitant hypertension and dyslipidemia: the respond trial. Journal of Clinical Pharmacology 2007;47(12):1555-69. - PubMed
Raal 2000 {published data only}
    1. Raal FJ, Pappu AS, Illingworth DR, Pilcher GJ, Marais AD, Firth JC, et al. Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia. Atherosclerosis 2000;150(2):421-8. - PubMed
Raal 2003 {published data only}
    1. Raal FJ, Marais AD, Klepack E, Lovalvo J, McLain R, Heinonen T. Avasimibe, an ACAT inhibitor, enhances the lipid lowering effect of atorvastatin in subjects with homozygous familial hypercholesterolemia. Atherosclerosis 2003;171(2):273-9. - PubMed
Raison 2002 {published data only}
    1. Raison J, Rudnichi A, Safar ME. Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study. Journal of Human Hypertension 2002;16(10):705-10. - PubMed
Reiter 2005 {published data only}
    1. Reiter M, Wirth S, Pourazim A, Baghestanian M, Minar E, Bucek RA. Statin therapy has no significant effect on skin tissue cholesterol: results from a prospective randomized trial. Clinical Chemistry 2005;51(1):252-4. - PubMed
Renders 2001 {published data only}
    1. Renders L, Mayer-Kadner I, Koch C, Scharffe S, Burkhardt K, Veelken R, et al. Efficacy and drug interactions of the new HMG-CoA reductase inhibitors cerivastatin and atorvastatin in CsA-treated renal transplant recipients. Nephrology, Dialysis, Transplantation 2001;16(1):141-6. - PubMed
Riahi 2006 {published data only}
    1. Riahi S, Schmidt EB, Amanavicius N, Karmisholt J, Jensen HS, Christoffersen RP, et al. The effect of atorvastatin on heart rate variability and lipoproteins in patients treated with coronary bypass surgery. International Journal of Cardiology 2006;111(3):436-41. - PubMed
Rosenson 2009 {published data only}
    1. Rosenson RS, Otvos JD, Hsia J. Effects of rosuvastatin and atorvastatin on LDL and HDL particle concentrations in patients with metabolic syndrome: a randomized, double-blind, controlled study. Diabetes Care 2009;32(6):1087-91. - PMC - PubMed
Sadik 2010 {published data only}
    1. Sadik HY, Moore TL, Vail A, Murray A, Anderson M, Blann A, et al. Lack of effect of 8 weeks atorvastatin on microvascular endothelial function in patients with systemic sclerosis. Rheumatology 2010;49(5):990-6. [MEDLINE: ] - PubMed
Samentzas 2015 {published data only}
    1. Samentzas AA, Sionis G, Papadimitriou D, Papasaikas D, Blazakis G, Paschalis A, et al. The effect of statins in erectile dysfunction. European Journal of Heart Failure 2015;17(Supplement 1):243.
Samy 2011 {published data only}
    1. Samy W, Hassanian MA. Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin. Arab Journal of Gastroenterology 2011;12(2):80-5. - PubMed
Sardo 2002 {published data only}
    1. Sardo MA, Castaldo M, Cinquegrani M, Bonaiuto M, Maesano A, Versace A, et al. Effects of atorvastatin treatment on sICAM-1 and plasma nitric oxide levels in hypercholesterolemic subjects. Clinical & Applied Thrombosis/Hemostasis 2002;8(3):257-63. [MEDLINE: ] - PubMed
Sardo 2005 {published data only}
    1. Sardo MA, Campo S, Bonaiuto M, Bonaiuto A, Saitta C, Trimarchi G, et al. Antioxidant effect of atorvastatin is independent of PON1 gene T(-107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients. Current Medical Research & Opinion 2005;21(5):777-84. [MEDLINE: ] - PubMed
Sasmazel 2010 {published data only}
    1. Sasmazel A, Baysal A, Fedekar A, Buyukbayrak F, Bugra O, Erdem H, et al. The effect of statin therapy on stimulation of endothelium-derived nitric oxide before and after coronary artery bypass surgery. Heart Surgery Forum 2010;13(4):E243-6. - PubMed
Sathyapalan 2019 {published data only}
    1. Sathyapalan T, Hobkirk JP, Javed Z, Carroll S, Coady AM, Pemberton P, et al. The effect of atorvastatin (and subsequent metformin) on adipose tissue acylation-stimulatory-protein concentration and inflammatory biomarkers in overweight/obese women with polycystic ovary syndrome. Frontiers in Endocrinology 2019;10(JUN):Article Number: 394. - PMC - PubMed
Schaefer 2002 {published data only}
    1. Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JA, Seman LJ, et al. Effects of atorvastatin on fasting and postprandial lipoprotein subclasses in coronary heart disease patients versus control subjects. American Journal of Cardiology 2002;90(7):689-96. - PubMed
Schaefer 2004 {published data only}
    1. Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JL, Seman LJ, et al. Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. American Journal of Cardiology 2004;93(1):31-9. - PubMed
Schaefer 2005 {published data only}
    1. Schaefer EJ, McNamara JR, Asztalos BF, Tayler T, Daly JA, Gleason JL, et al. Effects of atorvastatin versus other statins on fasting and postprandial C-reactive protein and lipoprotein-associated phospholipase A2 in patients with coronary heart disease versus control subjects. American Journal of Cardiology 2005;95(9):1025-32. - PubMed
Schanberg 2012 {published data only}
    1. Schanberg LE, Sandborg C, Barnhart HX, Ardoin SP, Yow E, Evans GW, et al. Use of atorvastatin in systemic lupus erythematosus in children and adolescents. Arthritis & Rheumatism 2012;64(1):285-96. [MEDLINE: ] - PMC - PubMed
Schneider 2004 {published data only}
    1. Schneider JG, Eynatten M, Parhofer KG, Volkmer JE, Schiekofer S, Hamann A, et al. Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo. Atherosclerosis 2004;175(2):325-31. - PubMed
Schrott 1998 {published data only}
    1. Schrott H, Fereshetian AG, Knopp RH, Bays H, Jones PH, Littlejohn III TW, et al. A multicenter, placebo-controlled, dose-ranging study of atorvastatin. Journal of Cardiovascular Pharmacology & Therapeutics 1998;3(2):119-24. [MEDLINE: ] - PubMed
Sdringola 2008 {published data only}
    1. Sdringola S, Gould KL, Zamarka LG, McLain R, Garner J. A 6 month randomized, double blind, placebo controlled, multi-center trial of high dose atorvastatin on myocardial perfusion abnormalities by positron emission tomography in coronary artery disease. American Heart Journal 2008;155(2):245-53. - PubMed
See 2003 {published data only}
    1. See VY, DeNofrio D, Goldberg L, Chang G, Sasseen B, Kolansky DM, et al. Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction. American Journal of Cardiology 2003;92(1):11-5. - PubMed
Sever 2003 {published data only}
    1. Sever PS, Dahlof B, Poulter N R, Wedel H, Beevers G, Caulfield M, et al for the ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trials-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003;361(9364):1149-58. [MEDLINE: ] - PubMed
Sever 2005 {published data only}
    1. Sever PS, Poulter NR, Dahlof B, Wedel H, Anglo-Scandinavian Cardiac Outcomes Trial Investigators. Different time course for prevention of coronary and stroke events by atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA). American Journal of Cardiology 2005;96(5A):39F-44F. [MEDLINE: ] - PubMed
Sever 2010 {published data only}
    1. Sever PS, Poulter NR, Dahlof B, Wedel H, ASCOT Investigators. Antihypertensive therapy and the benefits of atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial: lipid-lowering arm extension. Journal of Hypertension 2010;27(5):947-54. - PubMed
Sharma 2001 {published data only}
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Sillesen 2007a {published data only}
    1. Sillesen H, Amarenco P, Szarek M, Callahan A, Goldstein LB, Hennerici M, et al. Atorvastatin treatment in patients with carotid stenosis is associated with a marked reduction in the risk of stroke, cardiac events and endarterectomy: a substudy of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke; a journal of cerebral circulation 2007;38(2):457. [CENTRAL: CN-00603188]
Sillesen 2007b {published data only}
    1. Sillesen H, Fernandes JG, Berwanger O, Szarek M, Amarenco P, Callahan A, et al. Atorvastatin treatment in patients with carotid stenosis is associated with a marked reduction in the risk of stroke, cardiovascular events and carotid revascularisation procedures. A substudy of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial. Cerebrovascular diseases (basel, switzerland) 2007;23(Suppl 2):55. [CENTRAL: CN-00603199]
Sillesen 2008 {published data only}
    1. Sillesen H, Amarenco P, Hennerici M G, Callahan A, Goldstein L B, Zivin J, et al for the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial. Stroke 2008;39(12):3297-302. [MEDLINE: ] - PubMed
Singh 2008 {published data only}
    1. Singh U, Devaraj S, Jialal I, Siegel D. Comparison effect of atorvastatin (10 versus 80 mg) on biomarkers of inflammation and oxidative stress in subjects with metabolic syndrome. American Journal of Cardiology 2008;102(3):321-5. - PMC - PubMed
Sinski 2009 {published data only}
    1. Sinski M, Lewandowski J, Ciarka A, Bidiuk J, Abramczyk P, Dobosiewicz A, et al. Atorvastatin reduces sympathetic activity and increases baroreceptor reflex sensitivity in patients with hypercholesterolaemia and systemic arterial hypertension. Kardiologia Polska 2009;67(6):613-20. - PubMed
Soedamah‐Muthu 2003 {published data only}
    1. Soedamah-Muthu SS, Colhoun HM, Thomason MJ, Betteridge DJ, Durrington PN, Hitman GA, et al. The effect of atorvastatin on serum lipids, lipoproteins and NMR spectroscopy defined lipoprotein subclasses in type 2 diabetic patients with ischaemic heart disease. Atherosclerosis 2003;167(2):243-55. - PubMed
Soedamah‐Muthu 2015 {published data only}
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Sola 2006 {published data only}
    1. Sola S, Mir MQ, Lerakis S, Tandon N, Khan BV. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. Journal of the American College of Cardiology 2006;47(2):332-7. - PubMed
Solem 2006 {published data only}
    1. Solem J, Levin M, Karlsson T, Grip L, Albertsson P, Wiklund O. Composition of coronary plaques obtained by directional atherectomy in stable angina: its relation to serum lipids and statin treatment. Journal of Internal Medicine 2006;259(3):267-75. - PubMed
Sparks 2005 {published data only}
    1. Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Petanceska S, et al. Atorvastatin therapy lowers circulating cholesterol but not free radical activity in advance of identifiable clinical benefit in the treatment of mild-to-moderate AD. Current Alzheimer Research 2005;2(3):343-53. - PubMed
Sposito 2003 {published data only}
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Stalenhoef 2005 {published data only}
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Stefanadi 2009 {published data only}
    1. Stefanadi E, Tousoulis D, Antoniades C, Katsi V, Bosinakou E, Vavuranakis E, et al. Early initiation of low-dose atorvastatin treatment after an acute ST-elevated myocardial infarction, decreases inflammatory process and prevents endothelial injury and activation. International Journal of Cardiology 2009;133(2):266-8. - PubMed
Stein 2012 {published data only}
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Strey 2005 {published data only}
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Strey 2006 {published data only}
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Suleiman 2012 {published data only}
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Szramka 2007 {published data only}
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Tan 2002 {published data only}
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Tanaka 2001 {published data only}
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Tanaka 2009 {published data only}
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Taneva 2006 {published data only}
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Tannous 1999 {published data only}
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Tanriverdi 2005 {published data only}
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Tantikosoom 2005 {published data only}
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Tehrani 2010 {published data only}
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Teshima 2009 {published data only}
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Tousoulis 2005a {published data only}
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Tousoulis 2005b {published data only}
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Tousoulis 2005c {published data only}
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Tousoulis 2006a {published data only}
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Tousoulis 2006b {published data only}
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Tousoulis 2007 {published data only}
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Tousoulis 2010 {published data only}
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Tousoulis 2011 {published data only}
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Tremblay 2011 {published data only}
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References to other published versions of this review

Shawish 2018
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