The Pleiotropic Effects of Statins in Endocrine Disorders

Author(s): Javier A. De La Cruz, Christos G. Mihos, Sofia A. Horvath, Orlando Santana*.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 19 , Issue 6 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: The 3-Hydroxy-3-MethylGlutaryl-CoA reductase inhibitors, better known as statins, are used extensively in the treatment of dyslipidemia and cardiovascular risk reduction. They have also demonstrated a variety of non-lipid lowering, or pleiotropic effects. Pertaining to the endocrine system the benefits of statins can extend to patients with the polycystic ovarian syndrome and thyroid disease. However, there is also increasing evidence that statin use can lead to deleterious effects in different organs, including worsening glycemia and the development of diabetes mellitus.

Objective: The aim of this review is to describe the most relevant and updated evidence regarding the pleiotropic effects of statins in endocrine disorders.

Methods: We did a systematic review of scientific articles published in PubMed regarding the effects of statins on the different aspects of the endocrine system up until June 5th of 2018.

Results: We identified preliminarily 61 publications, of which 4 were excluded due to having abstract format only, and 5 were excluded for not containing pertinent information to the study.

Conclusion: Several aspects of the endocrine system have been shown to be influenced by the pleiotropic effects that statins exert, however, the benefits of statins on cardiovascular morbidity and mortality largely outweigh this deleterious effect, and statin therapy should continue to be recommended.

Keywords: Endocrine disorders, HMG-CoA reductase inhibitors, pleiotropic effects, statins, diabetes mellitus, hyperglycemia.

[1]
Stone, N.J.; Robinson, J.G.; Lichtenstein, A.H.; Bairey Merz, C.N.; Blum, C.B.; Eckel, R.H.; Goldberg, A.C.; Gordon, D.; Levy, D.; Lloyd-Jones, D.M.; McBride, P.; Schwartz, J.S.; Shero, S.T.; Smith, S.C., Jr; Watson, K.; Wilson, P.W. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol., 2014, 63(25 Pt B), 2889-2934.
[http://dx.doi.org/10.1016/j.jacc.2013.11.002] [PMID: 24239923]
[2]
Nicholls, S.J.; Ballantyne, C.M.; Barter, P.J.; Chapman, M.J.; Erbel, R.M.; Libby, P.; Raichlen, J.S.; Uno, K.; Borgman, M.; Wolski, K.; Nissen, S.E. Effect of two intensive statin regimens on progression of coronary disease. N. Engl. J. Med., 2011, 365(22), 2078-2087.
[http://dx.doi.org/10.1056/NEJMoa1110874] [PMID: 22085316]
[3]
Nissen, S.E.; Tuzcu, E.M.; Schoenhagen, P.; Crowe, T.; Sasiela, W.J.; Tsai, J.; Orazem, J.; Magorien, R.D.; O’Shaughnessy, C.; Ganz, P. Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N. Engl. J. Med., 2005, 352(1), 29-38.
[http://dx.doi.org/10.1056/NEJMoa042000] [PMID: 15635110]
[4]
LaRosa, J.C.; Grundy, S.M.; Waters, D.D.; Shear, C.; Barter, P.; Fruchart, J.C.; Gotto, A.M.; Greten, H.; Kastelein, J.J.P.; Shepherd, J.; Wenger, N.K. Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N. Engl. J. Med., 2005, 352(14), 1425-1435.
[http://dx.doi.org/10.1056/NEJMoa050461] [PMID: 15755765]
[5]
Ridker, P.M.; Danielson, E.; Fonseca, F.A.; Genest, J.; Gotto, A.M., Jr; Kastelein, J.J.; Koenig, W.; Libby, P.; Lorenzatti, A.J.; MacFadyen, J.G.; Nordestgaard, B.G.; Shepherd, J.; Willerson, J.T.; Glynn, R.J. JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med., 2008, 359(21), 2195-2207.
[http://dx.doi.org/10.1056/NEJMoa0807646] [PMID: 18997196]
[6]
Sacks, F.M.; Pfeffer, M.A.; Moye, L.A.; Rouleau, J.L.; Rutherford, J.D.; Cole, T.G.; Brown, L.; Warnica, J.W.; Arnold, J.M.; Wun, C.C.; Davis, B.R.; Braunwald, E. Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N. Engl. J. Med., 1996, 335(14), 1001-1009.
[http://dx.doi.org/10.1056/NEJM199610033351401] [PMID: 8801446]
[7]
Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N. Engl. J. Med., 1998, 339(19), 1349-1357.
[http://dx.doi.org/10.1056/NEJM199811053391902] [PMID: 9841303]
[8]
Shepherd, J.; Cobbe, S.M.; Ford, I.; Isles, C.G.; Lorimer, A.R.; MacFarlane, P.W.; McKillop, J.H.; Packard, C.J. West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N. Engl. J. Med., 1995, 333(20), 1301-1307.
[http://dx.doi.org/10.1056/NEJM199511163332001] [PMID: 7566020]
[9]
Mihos, C.G.; Pineda, A.M.; Santana, O. Cardiovascular effects of statins, beyond lipid-lowering properties. Pharmacol. Res., 2014, 88, 12-19.
[http://dx.doi.org/10.1016/j.phrs.2014.02.009] [PMID: 24631782]
[10]
Treasure, C.B.; Klein, J.L.; Weintraub, W.S.; Talley, J.D.; Stillabower, M.E.; Kosinski, A.S.; Zhang, J.; Boccuzzi, S.J.; Cedarholm, J.C.; Alexander, R.W. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N. Engl. J. Med., 1995, 332(8), 481-487.
[http://dx.doi.org/10.1056/NEJM199502233320801] [PMID: 7830728]
[11]
Liuni, A.; Luca, M.C.; Di Stolfo, G.; Uxa, A.; Mariani, J.A.; Gori, T.; Parker, J.D. Coadministration of atorvastatin prevents nitroglycerin-induced endothelial dysfunction and nitrate tolerance in healthy humans. J. Am. Coll. Cardiol., 2011, 57(1), 93-98.
[http://dx.doi.org/10.1016/j.jacc.2010.07.037] [PMID: 21185507]
[12]
Liuni, A.; Luca, M.C.; Gori, T.; Parker, J.D. Rosuvastatin prevents conduit artery endothelial dysfunction induced by ischemia and reperfusion by a cyclooxygenase-2-dependent mechanism. J. Am. Coll. Cardiol., 2010, 55(10), 1002-1006.
[http://dx.doi.org/10.1016/j.jacc.2009.11.046] [PMID: 20202516]
[13]
Böger, G.I.; Rudolph, T.K.; Maas, R.; Schwedhelm, E.; Dumbadze, E.; Bierend, A.; Benndorf, R.A.; Böger, R.H. Asymmetric dimethylarginine determines the improvement of endothelium-dependent vasodilation by simvastatin: Effect of combination with oral L-arginine. J. Am. Coll. Cardiol., 2007, 49(23), 2274-2282.
[http://dx.doi.org/10.1016/j.jacc.2007.02.051] [PMID: 17560293]
[14]
Patti, G.; Chello, M.; Pasceri, V.; Colonna, D.; Nusca, A.; Miglionico, M.; D’Ambrosio, A.; Covino, E.; Di Sciascio, G. Protection from procedural myocardial injury by atorvastatin is associated with lower levels of adhesion molecules after percutaneous coronary intervention: results from the ARMYDA-CAMs (Atorvastatin for Reduction of MYocardial Damage during Angioplasty-Cell Adhesion Molecules) substudy. J. Am. Coll. Cardiol., 2006, 48(8), 1560-1566.
[http://dx.doi.org/10.1016/j.jacc.2006.06.061] [PMID: 17045888]
[15]
Mihos, C.G.; Santana, O. Pleiotropic effects of the HMG-CoA reductase inhibitors. Int. J. Gen. Med., 2011, 4, 261-271.
[PMID: 21556312]
[16]
Mihos, C.G.; Artola, R.T.; Santana, O. The Pleiotropic Effects of the HMG-CoA reductase inhibitors in rheumatologic disorders: a comprehensive review. Rheum. Int, 2012, 32, 287-294.
[http://dx.doi.org/10.1007/s00296-011-2008-6] [PMID: 21805349]
[17]
Zeichner, S.; Mihos, C.G.; Santana, O. The pleiotropic effects and therapeutic potential of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in malignancies: a comprehensive review. J. Cancer Res. Ther., 2012, 8(2), 176-183.
[http://dx.doi.org/10.4103/0973-1482.98967] [PMID: 22842358]
[18]
Yanuck, D.; Mihos, C.G.; Santana, O. Mechanisms and clinical evidence of the pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in neurologic disorders: a comprehensive review. Int. J. Neurosci., 2012, 122, 619-629.
[http://dx.doi.org/10.3109/00207454.2012.704455] [PMID: 22720798]
[19]
Cortes-Bergoderi, M.; Pineda, A.M.; Santana, O. The pleiotropic effects and therapeutic potential of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in gastrointestinal tract disorders: A comprehensive review. J. Gastrointestin. Liver Dis., 2013, 22(2), 199-204.
[PMID: 23799219]
[20]
Gomez, S.I.; Mihos, C.G.; Pineda, A.M.; Santana, O. The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in renal disease. Int. J. Nephrol. Renovasc. Dis., 2014, 7, 123-130.
[PMID: 24729724]
[21]
Krishna, R.K.; Issa, O.; Saha, D.; Macedo, F.Y.B.; Correal, B.; Santana, O. Pleiotropic effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in pulmonary diseases: A comprehensive review. Pulm. Pharmacol. Ther., 2015, 30, 134-140.
[http://dx.doi.org/10.1016/j.pupt.2014.08.006] [PMID: 25173913]
[22]
Cho, Y.; Choe, E.; Lee, Y.H.; Seo, J.W.; Choi, Y.; Yun, Y.; Wang, H.J.; Ahn, C.W.; Cha, B.S.; Lee, H.C.; Kang, E.S. Risk of diabetes in patients treated with HMG-CoA reductase inhibitors. Metabolism, 2015, 64(4), 482-488.
[http://dx.doi.org/10.1016/j.metabol.2014.09.008] [PMID: 25312577]
[23]
Puurunen, J.; Piltonen, T.; Puukka, K.; Ruokonen, A.; Savolainen, M.J.; Bloigu, R.; Morin-Papunen, L.; Tapanainen, J.S. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. J. Clin. Endocrinol. Metab., 2013, 98(12), 4798-4807.
[http://dx.doi.org/10.1210/jc.2013-2674] [PMID: 24152688]
[24]
Baudrand, R.; Pojoga, L.H.; Vaidya, A.; Garza, A.E.; Vöhringer, P.A.; Jeunemaitre, X.; Hopkins, P.N.; Yao, T.M.; Williams, J.; Adler, G.K.; Williams, G.H. Statin use and adrenal aldosterone production in hypertensive and diabetic subjects. Circulation, 2015, 132(19), 1825-1833.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016759] [PMID: 26432671]
[25]
Pons-Rejraji, H.; Brugnon, F.; Sion, B.; Maqdasy, S.; Gouby, G.; Pereira, B.; Marceau, G.; Gremeau, A.S.; Drevet, J.; Grizard, G.; Janny, L.; Tauveron, I. Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: A pilot prospective clinical trial. Reprod. Biol. Endocrinol., 2014, 12, 65.
[http://dx.doi.org/10.1186/1477-7827-12-65] [PMID: 25016482]
[26]
Tada, Y.; Hayashi, T.; Iwaki, Y.; Karita, M.; Taguchi, S.; Funabiki, M.; Nakamura, Y. Transient azoospermia following rosuvastatin medication for hypercholesterolemia. Clin. Exp. Obstet. Gynecol., 2015, 42(4), 545-546.
[PMID: 26411232]
[27]
Koh, K.K.; Quon, M.J.; Han, S.H.; Lee, Y.; Kim, S.J.; Shin, E.K. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J. Am. Coll. Cardiol., 2010, 55(12), 1209-1216.
[http://dx.doi.org/10.1016/j.jacc.2009.10.053] [PMID: 20298928]
[28]
Preiss, D.; Seshasai, S.R.; Welsh, P.; Murphy, S.A.; Ho, J.E.; Waters, D.D.; DeMicco, D.A.; Barter, P.; Cannon, C.P.; Sabatine, M.S.; Braunwald, E.; Kastelein, J.J.; de Lemos, J.A.; Blazing, M.A.; Pedersen, T.R.; Tikkanen, M.J.; Sattar, N.; Ray, K.K. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA, 2011, 305(24), 2556-2564.
[http://dx.doi.org/10.1001/jama.2011.860] [PMID: 21693744]
[29]
Waters, D.D.; Ho, J.E.; Boekholdt, S.M.; DeMicco, D.A.; Kastelein, J.J.; Messig, M.; Breazna, A.; Pedersen, T.R. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J. Am. Coll. Cardiol., 2013, 61(2), 148-152.
[http://dx.doi.org/10.1016/j.jacc.2012.09.042] [PMID: 23219296]
[30]
Ridker, P.M.; Pradhan, A.; MacFadyen, J.G.; Libby, P.; Glynn, R.J.; Glynn, R.J. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet, 2012, 380(9841), 565-571.
[http://dx.doi.org/10.1016/S0140-6736(12)61190-8] [PMID: 22883507]
[31]
Sattar, N.; Preiss, D.; Murray, H.M.; Welsh, P.; Buckley, B.M.; de Craen, A.J.; Seshasai, S.R.; McMurray, J.J.; Freeman, D.J.; Jukema, J.W.; Macfarlane, P.W.; Packard, C.J.; Stott, D.J.; Westendorp, R.G.; Shepherd, J.; Davis, B.R.; Pressel, S.L.; Marchioli, R.; Marfisi, R.M.; Maggioni, A.P.; Tavazzi, L.; Tognoni, G.; Kjekshus, J.; Pedersen, T.R.; Cook, T.J.; Gotto, A.M.; Clearfield, M.B.; Downs, J.R.; Nakamura, H.; Ohashi, Y.; Mizuno, K.; Ray, K.K.; Ford, I. Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials. Lancet, 2010, 375(9716), 735-742.
[http://dx.doi.org/10.1016/S0140-6736(09)61965-6] [PMID: 20167359]
[32]
Corrao, G.; Ibrahim, B.; Nicotra, F.; Soranna, D.; Merlino, L.; Catapano, A.L.; Tragni, E.; Casula, M.; Grassi, G.; Mancia, G. Statins and the risk of diabetes: evidence from a large population-based cohort study. Diabetes Care, 2014, 37(8), 2225-2232.
[http://dx.doi.org/10.2337/dc13-2215] [PMID: 24969582]
[33]
Danaei, G.; García Rodríguez, L.A.; Fernandez Cantero, O.; Hernán, M.A. Statins and risk of diabetes: an analysis of electronic medical records to evaluate possible bias due to differential survival. Diabetes Care, 2013, 36(5), 1236-1240.
[http://dx.doi.org/10.2337/dc12-1756] [PMID: 23248196]
[34]
Swerdlow, D.I.; Preiss, D.; Kuchenbaecker, K.B.; Holmes, M.V.; Engmann, J.E.L.; Shah, T.; Sofat, R.; Stender, S.; Johnson, P.C.; Scott, R.A.; Leusink, M.; Verweij, N.; Sharp, S.J.; Guo, Y.; Giambartolomei, C.; Chung, C.; Peasey, A.; Amuzu, A.; Li, K.; Palmen, J.; Howard, P.; Cooper, J.A.; Drenos, F.; Li, Y.R.; Lowe, G.; Gallacher, J.; Stewart, M.C.; Tzoulaki, I.; Buxbaum, S.G. van der A, D.L.; Forouhi, N.G.; Onland-Moret, N.C.; van der Schouw, Y.T.; Schnabel, R.B.; Hubacek, J.A.; Kubinova, R.; Baceviciene, M.; Tamosiunas, A.; Pajak, A.; Topor-Madry, R.; Stepaniak, U.; Malyutina, S.; Baldassarre, D.; Sennblad, B.; Tremoli, E.; de Faire, U.; Veglia, F.; Ford, I.; Jukema, J.W.; Westendorp, R.G.; de Borst, G.J.; de Jong, P.A.; Algra, A.; Spiering, W.; Maitland-van der Zee, A.H.; Klungel, O.H.; de Boer, A.; Doevendans, P.A.; Eaton, C.B.; Robinson, J.G.; Duggan, D.; Kjekshus, J.; Downs, J.R.; Gotto, A.M.; Keech, A.C.; Marchioli, R.; Tognoni, G.; Sever, P.S.; Poulter, N.R.; Waters, D.D.; Pedersen, T.R.; Amarenco, P.; Nakamura, H.; McMurray, J.J.; Lewsey, J.D.; Chasman, D.I.; Ridker, P.M.; Maggioni, A.P.; Tavazzi, L.; Ray, K.K.; Seshasai, S.R.; Manson, J.E.; Price, J.F.; Whincup, P.H.; Morris, R.W.; Lawlor, D.A.; Smith, G.D.; Ben-Shlomo, Y.; Schreiner, P.J.; Fornage, M.; Siscovick, D.S.; Cushman, M.; Kumari, M.; Wareham, N.J.; Verschuren, W.M.; Redline, S.; Patel, S.R.; Whittaker, J.C.; Hamsten, A.; Delaney, J.A.; Dale, C.; Gaunt, T.R.; Wong, A.; Kuh, D.; Hardy, R.; Kathiresan, S.; Castillo, B.A.; van der Harst, P.; Brunner, E.J.; Tybjaerg-Hansen, A.; Marmot, M.G.; Krauss, R.M.; Tsai, M.; Coresh, J.; Hoogeveen, R.C.; Psaty, B.M.; Lange, L.A.; Hakonarson, H.; Dudbridge, F.; Humphries, S.E.; Talmud, P.J.; Kivimäki, M.; Timpson, N.J.; Langenberg, C.; Asselbergs, F.W.; Voevoda, M.; Bobak, M.; Pikhart, H.; Wilson, J.G.; Reiner, A.P.; Keating, B.J.; Hingorani, A.D.; Sattar, N. DIAGRAM Consortium. MAGIC Consortium. InterAct Consortium. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet, 2015, 385(9965), 351-361.
[http://dx.doi.org/10.1016/S0140-6736(14)61183-1] [PMID: 25262344]
[35]
Waters, D.D.; Ho, J.E.; DeMicco, D.A.; Breazna, A.; Arsenault, B.J.; Wun, C.C.; Kastelein, J.J.; Colhoun, H.; Barter, P. Predictors of new-onset diabetes in patients treated with atorvastatin: Results from 3 large randomized clinical trials. J. Am. Coll. Cardiol., 2011, 57(14), 1535-1545.
[http://dx.doi.org/10.1016/j.jacc.2010.10.047] [PMID: 21453832]
[36]
Yada, T.; Nakata, M.; Shiraishi, T.; Kakei, M. Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+ signalling and insulin secretion due to blockade of L-type Ca2+ channels in rat islet beta-cells. Br. J. Pharmacol., 1999, 126(5), 1205-1213.
[http://dx.doi.org/10.1038/sj.bjp.0702397] [PMID: 10205010]
[37]
Yaluri, N.; Modi, S.; López Rodríguez, M.; Stančáková, A.; Kuusisto, J.; Kokkola, T.; Laakso, M. Simvastatin impairs insulin secretion by multiple mechanisms in MIN6 cells. PLoS One, 2015, 10(11)e0142902
[http://dx.doi.org/10.1371/journal.pone.0142902] [PMID: 26561346]
[38]
Brault, M.; Ray, J.; Gomez, Y.H.; Mantzoros, C.S.; Daskalopoulou, S.S. Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism, 2014, 63(6), 735-745.
[http://dx.doi.org/10.1016/j.metabol.2014.02.014] [PMID: 24641882]
[39]
Ganesan, S.; Ito, M.K. Coenzyme Q10 ameliorates the reduction in GLUT4 transporter expression induced by simvastatin in 3T3-L1 adipocytes. Metab. Syndr. Relat. Disord., 2013, 11(4), 251-255.
[http://dx.doi.org/10.1089/met.2012.0177] [PMID: 23496027]
[40]
Nowis, D.; Malenda, A.; Furs, K.; Oleszczak, B.; Sadowski, R.; Chlebowska, J.; Firczuk, M.; Bujnicki, J.M.; Staruch, A.D.; Zagozdzon, R.; Glodkowska-Mrowka, E.; Szablewski, L.; Golab, J. Statins impair glucose uptake in human cells. BMJ Open Diabetes Res. Care, 2014, 2(1)e000017
[http://dx.doi.org/10.1136/bmjdrc-2014-000017] [PMID: 25452863]
[41]
Nakata, M.; Nagasaka, S.; Kusaka, I.; Matsuoka, H.; Ishibashi, S.; Yada, T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia, 2006, 49(8), 1881-1892.
[http://dx.doi.org/10.1007/s00125-006-0269-5] [PMID: 16685502]
[42]
Takaguri, A.; Satoh, K.; Itagaki, M.; Tokumitsu, Y.; Ichihara, K. Effects of atorvastatin and pravastatin on signal transduction related to glucose uptake in 3T3L1 adipocytes. J. Pharmacol. Sci., 2008, 107(1), 80-89.
[http://dx.doi.org/10.1254/jphs.FP0072403] [PMID: 18469500]
[43]
Naples, M.; Federico, L.M.; Xu, E.; Nelken, J.; Adeli, K. Effect of rosuvastatin on insulin sensitivity in an animal model of insulin resistance: evidence for statin-induced hepatic insulin sensitization. Atherosclerosis, 2008, 198(1), 94-103.
[http://dx.doi.org/10.1016/j.atherosclerosis.2007.11.003] [PMID: 18093597]
[44]
Valero-Muñoz, M.; Martín-Fernández, B.; Ballesteros, S.; Cachofeiro, V.; Lahera, V.; de Las Heras, N. [Rosuvastatin improves insulin sensitivity in overweight rats induced by high fat diet. Role of SIRT1 in adipose tissue] Clin. Investig. Arterioscler, 2014, 26(4), 161-167.
[PMID: 24612843]
[45]
Chan, D.C.; Pang, J.; Watts, G.F. Pathogenesis and management of the diabetogenic effect of statins: a role for adiponectin and coenzyme Q10? Curr. Atheroscler. Rep., 2015, 17(1), 472.
[http://dx.doi.org/10.1007/s11883-014-0472-7] [PMID: 25398645]
[46]
Arnaboldi, L.; Corsini, A. Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin. Atheroscler. Suppl., 2015, 16, 1-27.
[http://dx.doi.org/10.1016/S1567-5688(14)70002-9] [PMID: 25575403]
[47]
de Carvalho, L.S.F.; Campos, A.M.; Sposito, A.C. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors and Incident Type 2 Diabetes: A Systematic Review and Meta-analysis With Over 96,000 Patient-Years. Diabetes Care, 2018, 41(2), 364-367.
[http://dx.doi.org/10.2337/dc17-1464] [PMID: 29180351]
[48]
Roehrich, M.E.; Mooser, V.; Lenain, V.; Herz, J.; Nimpf, J.; Azhar, S.; Bideau, M.; Capponi, A.; Nicod, P.; Haefliger, J.A.; Waeber, G. Insulin-secreting beta-cell dysfunction induced by human lipoproteins. J. Biol. Chem., 2003, 278(20), 18368-18375.
[http://dx.doi.org/10.1074/jbc.M300102200] [PMID: 12594227]
[49]
Lotta, L.A.; Sharp, S.J.; Burgess, S.; Perry, J.R.B.; Stewart, I.D.; Willems, S.M.; Luan, J.; Ardanaz, E.; Arriola, L.; Balkau, B.; Boeing, H.; Deloukas, P.; Forouhi, N.G.; Franks, P.W.; Grioni, S.; Kaaks, R.; Key, T.J.; Navarro, C.; Nilsson, P.M.; Overvad, K.; Palli, D.; Panico, S.; Quirós, J.R.; Riboli, E.; Rolandsson, O.; Sacerdote, C.; Salamanca, E.C.; Slimani, N.; Spijkerman, A.M.; Tjonneland, A.; Tumino, R. van der A, D.L.; van der Schouw, Y.T.; McCarthy, M.I.; Barroso, I.; O’Rahilly, S.; Savage, D.B.; Sattar, N.; Langenberg, C.; Scott, R.A.; Wareham, N.J. Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes: A Meta-analysis. JAMA, 2016, 316(13), 1383-1391.
[http://dx.doi.org/10.1001/jama.2016.14568] [PMID: 27701660]
[50]
Sirmans, S.M.; Weidman-Evans, E.; Everton, V.; Thompson, D. Polycystic ovary syndrome and chronic inflammation: pharmacotherapeutic implications. Ann. Pharmacother., 2012, 46(3), 403-418.
[http://dx.doi.org/10.1345/aph.1Q514] [PMID: 22388330]
[51]
Repaci, A.; Gambineri, A.; Pasquali, R. The role of low-grade inflammation in the polycystic ovary syndrome. Mol. Cell. Endocrinol., 2011, 335(1), 30-41.
[http://dx.doi.org/10.1016/j.mce.2010.08.002] [PMID: 20708064]
[52]
Economou, F.; Xyrafis, X.; Christakou, C.; Diamanti-Kandarakis, E. The pluripotential effects of hypolipidemic treatment for polycystic ovary syndrome (PCOS): dyslipidemia, cardiovascular risk factors and beyond. Curr. Pharm. Des., 2011, 17(9), 908-921.
[http://dx.doi.org/10.2174/138161211795428821] [PMID: 21418035]
[53]
Goodman, N.F.; Cobin, R.H.; Futterweit, W.; Glueck, J.S.; Legro, R.S.; Carmina, E. American Association of Clinical Endocrinologists (AACE). American College of Endocrinology (ACE). Androgen Excess and PCOS Society. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - part 2. Endocr. Pract., 2015, 21(12), 1415-1426.
[http://dx.doi.org/10.4158/EP15748.DSCPT2] [PMID: 26642102]
[54]
Kodaman, P.H.; Duleba, A.J. HMG-CoA reductase inhibitors: Do they have potential in the treatment of polycystic ovary syndrome? Drugs, 2008, 68(13), 1771-1785.
[http://dx.doi.org/10.2165/00003495-200868130-00001] [PMID: 18729532]
[55]
Sathyapalan, T.; Shepherd, J.; Coady, A.M.; Kilpatrick, E.S.; Atkin, S.L. Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 2012, 97(11), 3951-3955.
[http://dx.doi.org/10.1210/jc.2012-2279] [PMID: 22879630]
[56]
Sun, J.; Yuan, Y.; Cai, R.; Sun, H.; Zhou, Y.; Wang, P.; Huang, R.; Xia, W.; Wang, S. An investigation into the therapeutic effects of statins with metformin on polycystic ovary syndrome: a meta-analysis of randomised controlled trials. BMJ Open, 2015, 5(3)e007280
[http://dx.doi.org/10.1136/bmjopen-2014-007280] [PMID: 25818277]
[57]
Gao, L.; Zhao, F.L.; Li, S.C. Statin is a reasonable treatment option for patients with Polycystic Ovary Syndrome: A meta-analysis of randomized controlled trials. Exp. Clin. Endocrinol. Diabetes, 2012, 120(6), 367-375.
[http://dx.doi.org/10.1055/s-0032-1304619] [PMID: 22639397]
[58]
Raval, A.D.; Hunter, T.; Stuckey, B.; Hart, R.J. Statins for women with polycystic ovary syndrome not actively trying to conceive. Cochrane Database Syst. Rev., 2011, 10.
[http://dx.doi.org/10.1002/14651858.CD008565.pub2]
[59]
Sokalska, A.; Piotrowski, P.C.; Rzepczynska, I.J.; Cress, A.; Duleba, A.J. Statins inhibit growth of human theca-interstitial cells in PCOS and non-PCOS tissues independently of cholesterol availability. J. Clin. Endocrinol. Metab., 2010, 95(12), 5390-5394.
[http://dx.doi.org/10.1210/jc.2010-0770] [PMID: 20826585]
[60]
Chon, M.G.; Suk, J.H.; Oh, K.H.; Kim, K.I.; Kim, Y.J.; Lee, H.G.; Kim, S.M.; Cho, K.I.; Kim, M.K.; Kim, T.I. Influence of long-term statin use in type 2 diabetic patients on thyroid nodularity in iodine-sufficient area. Exp. Clin. Endocrinol. Diabetes, 2011, 119(8), 497-501.
[http://dx.doi.org/10.1055/s-0031-1283123] [PMID: 21915844]
[61]
Cappelli, C.; Castellano, M.; Pirola, I.; De Martino, E.; Gandossi, E.; Delbarba, A.; Salvi, A.; Rosei, E.A. Reduced thyroid volume and nodularity in dyslipidaemic patients on statin treatment. Clin. Endocrinol. (Oxf.), 2008, 68(1), 16-21.
[http://dx.doi.org/10.1111/j.1365-2265.2007.02982.x] [PMID: 17666091]
[62]
Gullu, S.; Emral, R.; Bastemir, M.; Parkes, A.B.; Lazarus, J.H. In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto’s thyroiditis. Eur. J. Endocrinol., 2005, 153(1), 41-48.
[http://dx.doi.org/10.1530/eje.1.01941] [PMID: 15994744]
[63]
Wu, X.; Schott, M.; Liu, C.; Qian, C.; Mao, X.; Xu, K.; Jiang, J.; Xu, Y.; Shen, M.; Papewalis, C.; Scherbaum, W.A.; Liu, C. Statins decrease the aberrant HLA-DR expression on thyrocytes from patients with Hashimoto’s thyroiditis. Horm. Metab. Res., 2008, 40(12), 838-841.
[http://dx.doi.org/10.1055/s-2008-1081500] [PMID: 18686224]
[64]
Di Matola, T.; D’Ascoli, F.; Luongo, C.; Bifulco, M.; Rossi, G.; Fenzi, G.; Vitale, M. Lovastatin-induced apoptosis in thyroid cells: involvement of cytochrome c and lamin B. Eur. J. Endocrinol., 2001, 145(5), 645-650.
[http://dx.doi.org/10.1530/eje.0.1450645] [PMID: 11720884]
[65]
Dobs, A.S.; Schrott, H.; Davidson, M.H.; Bays, H.; Stein, E.A.; Kush, D.; Wu, M.; Mitchel, Y.; Illingworth, R.D. Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia. Metabolism, 2000, 49(9), 1234-1238.
[http://dx.doi.org/10.1053/meta.2000.7716a] [PMID: 11016911]
[66]
Travia, D.; Tosi, F.; Negri, C.; Faccini, G.; Moghetti, P.; Muggeo, M. Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidogenesis by adrenals and gonads. J. Clin. Endocrinol. Metab., 1995, 80(3), 836-840.
[PMID: 7883839]
[67]
Bernini, G.P.; Argenio, G.F.; Gasperi, M.; Vivaldi, M.S.; Franchi, F.; Salvetti, A. Effects of long-term simvastatin treatment on testicular and adrenal steroidogenesis in hypercholesterolemic patients. J. Endocrinol. Invest., 1994, 17(4), 227-233.
[http://dx.doi.org/10.1007/BF03348962] [PMID: 7930373]
[68]
Santini, S.A.; Carrozza, C.; Lulli, P.; Zuppi, C. CarloTonolo, G.; Musumeci, S. Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia. J. Atheroscler. Thromb., 2003, 10(3), 160-164.
[http://dx.doi.org/10.5551/jat.10.160] [PMID: 14564085]
[69]
Mondul, A.M.; Selvin, E.; Rohrmann, S.; Menke, A.; Feinleib, M.; Kanarek, N.; Rifai, N.; Dobs, A.S.; Platz, E.A. Association of serum cholesterol and cholesterol-lowering drug use with serum sex steroid hormones in men in NHANES III. Cancer Causes Control, 2010, 21(10), 1575-1583.
[http://dx.doi.org/10.1007/s10552-010-9586-6] [PMID: 20512526]
[70]
Davis, R.; Reveles, K.R.; Ali, S.K.; Mortensen, E.M.; Frei, C.R.; Mansi, I. Statins and male sexual health: A retrospective cohort analysis. J. Sex. Med., 2015, 12(1), 158-167.
[http://dx.doi.org/10.1111/jsm.12745] [PMID: 25421152]
[71]
Schooling, C.M.; Au Yeung, S.L.; Freeman, G.; Cowling, B.J. The effect of statins on testosterone in men and women: A systematic review and meta-analysis of randomized controlled trials. BMC Med., 2013, 11, 57.
[http://dx.doi.org/10.1186/1741-7015-11-57] [PMID: 23448151]
[72]
Singh, I.; Khan, M.; Key, L.; Pai, S. Lovastatin for X-linked adrenoleukodystrophy. N. Engl. J. Med., 1998, 339(10), 702-703.
[http://dx.doi.org/10.1056/NEJM199809033391012] [PMID: 9729143]
[73]
Verrips, A.; Willemsen, M.A.; Rubio-Gozalbo, E.; De Jong, J.; Smeitink, J.A. Simvastatin and plasma very-long-chain fatty acids in X-linked adrenoleukodystrophy. Ann. Neurol., 2000, 47(4), 552-553.
[http://dx.doi.org/10.1002/1531-8249(200004)47:4<552:AID-ANA28>3.0.CO;2-0] [PMID: 10762175]
[74]
Engelen, M.; Ofman, R.; Dijkgraaf, M.G.; Hijzen, M.; van der Wardt, L.A.; van Geel, B.M.; de Visser, M.; Wanders, R.J.; Poll-The, B.T.; Kemp, S. Lovastatin in X-linked adrenoleukodystrophy. N. Engl. J. Med., 2010, 362(3), 276-277.
[http://dx.doi.org/10.1056/NEJMc0907735] [PMID: 20089986]
[75]
Roberto, G.; Biagi, C.; Montanaro, N.; Koci, A.; Moretti, U.; Motola, D. Statin-associated gynecomastia: evidence coming from the Italian spontaneous ADR reporting database and literature. Eur. J. Clin. Pharmacol., 2012, 68(6), 1007-1011.
[http://dx.doi.org/10.1007/s00228-012-1218-5] [PMID: 22286160]
[76]
Oteri, A.; Catania, M.A.; Travaglini, R.; Russo, A.; Giustini, S.E.; Caputi, A.P.; Polimeni, G. Gynecomastia possibly induced by rosuvastatin. Pharmacotherapy, 2008, 28(4), 549-551.
[http://dx.doi.org/10.1592/phco.28.4.549] [PMID: 18363539]


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VOLUME: 19
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DOI: 10.2174/1871530319666190329115003
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