Skip to main content

Advertisement

Log in

Statins, hormones, and women: Benefits and drawbacks for atherosclerosis and osteoporosis

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Clinical trials have shown that 3-hydoxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, known as statins, significantly reduce the risk of both primary and secondary coronary heart disease events. Although these trials have included few women, the evidence suggests that statins are as effective in women as in men. The addition of hormone replacement therapy to statin therapy augments lowering of low-density lipoprotein cholesterol, but may not increase the favorable effects on clinical events achieved with statins alone. Finally, new data suggest that statins may also reduce the risk of osteoporotic fractures, a provocative finding still in need of verification by clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Maron DJ, Fazio S, Linton MF: Current perspectives on statins. Circulation 2000, 101:207–213.

    PubMed  CAS  Google Scholar 

  2. Ross R: Atherosclerosis—an inflammatory disease. N Engl J Med 1999, 340:115–126.

    Article  PubMed  CAS  Google Scholar 

  3. Bellosta S, Ferri N, Bernini F, et al.: Non-lipid-related effects of statins. Ann Med 2000, 32:164–176.

    PubMed  CAS  Google Scholar 

  4. Raiteri M, Arnaboldi L, McGeady P, et al.: Pharmacological control of the mevalonate pathway: effect on arterial smooth muscle cell proliferation. J Pharmacol Exp Ther 1997, 281:1144–1153.

    PubMed  CAS  Google Scholar 

  5. Laufs U, Liao JK: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 1998, 273:24266–24271.

    Article  PubMed  CAS  Google Scholar 

  6. Cummings SR, Bauer DC: Do statins prevent both cardiovascular disease and fracture? JAMA 2000, 283:3255–3257.

    Article  PubMed  CAS  Google Scholar 

  7. Russell RG, Rogers MJ, Frith JC, et al.: The pharmacology of bisphosphonates and new insights into their mechanisms of action. J Bone Miner Res 1999, 14(Suppl 2):53–65.

    PubMed  CAS  Google Scholar 

  8. Reszka AA, Halasy-Nagy JM, Masarachia PJ, Rodan GA: Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mstl kinase during apoptosis. A link between inhibition of the mevalonate pathway and regulation of an apoptosis-promoting kinase. J Biol Chem 1999, 274:34967–34973.

    Article  PubMed  CAS  Google Scholar 

  9. Fisher JE, Rogers MJ, Halasy JM, et al.: Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci USA 1999, 96:133–138.

    Article  PubMed  CAS  Google Scholar 

  10. Mundy G, Garrett R, Harris S, et al.: Stimulation of bone formation in vitro and in rodents by statins. Science 1999, 286:1946–1949.

    Article  PubMed  CAS  Google Scholar 

  11. Shepherd J, Cobbe SM, Ford I, et al.: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995, 333:1301–1307.

    Article  PubMed  CAS  Google Scholar 

  12. Downs JR, Clearfield M, Weis S, et al.: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. Results of AFCAPS/TexCAPS. JAMA 1998, 279:1615–1622.

    Article  PubMed  CAS  Google Scholar 

  13. Scandinavian Simvastatin Survival Study Group: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994, 344:1383–1389.

    Article  Google Scholar 

  14. Sacks FM, Pfeffer MA, Moye LE, et al.: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996, 335:1001–1009.

    Article  PubMed  CAS  Google Scholar 

  15. 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, 339:1349–1357.

    Article  Google Scholar 

  16. Sacks FM, Tonkin AM, Shepherd J, et al.: Effect of pravastatin on coronary disease risk events in subgroups defined by coronary risk factors. The Prospective Pravastatin Pooling Project. Circulation 2000, 102:1893–1900.

    PubMed  CAS  Google Scholar 

  17. LaRosa JC, He J, Vupputuri S: Effect of statins on risk of coronary disease. A meta-analysis of randomized controlled trials. JAMA 1999, 282:2340–2346.

    Article  PubMed  CAS  Google Scholar 

  18. Gerhard M, Ganz P: How do we explain the clinical benefits of estrogen? From bedside to bench. Circulation 1995, 92:5–8.

    PubMed  CAS  Google Scholar 

  19. Hulley S, Grady D, Bush T, et al.: Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998, 280:605–613.

    Article  PubMed  CAS  Google Scholar 

  20. Herrington DM, Reboussin DM, Brosnihan KB, et al.: Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med 2000, 343:522–529.

    Article  PubMed  CAS  Google Scholar 

  21. Grady D, Wenger NK, Herrington DM, et al.: Postmenopausal hormone therapy increases risk for venous thromboembolic disease: the Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2000, 139:689–696.

    Google Scholar 

  22. Colditz GA, Hankinson SE, Hunter DJ, et al.: The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995, 332:1589–1593.

    Article  PubMed  CAS  Google Scholar 

  23. Darling GM, Johns JA, McCloud PI, Davis SR: Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. N Engl J Med 1997, 337:595–601.

    Article  PubMed  CAS  Google Scholar 

  24. Sbarouni E, Kyriakides ZS, Kremastinos DT: The effect of hormone replacement therapy alone or in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease. J Am Coll Cardiol 1998, 32:1244–1250.

    Article  PubMed  CAS  Google Scholar 

  25. Herrington DM, Werbel BL, Riley WA, et al.: Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease. J Am Coll Cardiol 1999, 33:2030–2037.

    Article  PubMed  CAS  Google Scholar 

  26. Ohta H, Komukai S, Sugimoto I, et al.: Effect of a HMG-CoA reductase inhibitor combined with hormone replacement therapy on lipid metabolism in Japanese women with hypoestrogenic lipidemia: a multicenter double-blind controlled prospective study. Maturitas 1998, 29:163–171.

    Article  PubMed  CAS  Google Scholar 

  27. Davidson MH, Testolin LM, Maki KC, et al.: A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women. Arch Intern Med 1997, 157:1186–1192.

    Article  PubMed  CAS  Google Scholar 

  28. Herrington DM, Vittinghoff E, Hunninghake D, et al.: Effects of statin therapy on cardiovascular events and all-cause mortality in women in the Heart and Estrogen/progestin Replacement Study (HERS) (abstract). Circulation 2000, 102 (Suppl):II-837.

    Google Scholar 

  29. Chan KA, Andrade SE, Boles M, et al.: Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women. Lancet 2000, 355:2185–2188.

    Article  PubMed  CAS  Google Scholar 

  30. Wang PS, Solomon DH, Mogun H, Avorn J: HMG-CoA reductase inhibitors and the risk of hip fractures in the elderly. JAMA 2000, 283:3211–3216.

    Article  PubMed  CAS  Google Scholar 

  31. Meier CR, Schlienger RG, Kraenzlin ME, et al.: HMG-CoA reductase inhibitors and the risk of fractures. JAMA 2000, 283:3205–3210.

    Article  PubMed  CAS  Google Scholar 

  32. Van Staa TP, Wegman SL, de Vries F, et al.: Use of statins and risk of fractures [abstract]. J Bone Miner Res 2000, 15(Suppl 1):S155.

    Google Scholar 

  33. Bauer DC, Mundy GR, Jamal SA, et al.: Statin use, bone mass and fracture: an analysis of two prospective studies [abstract]. J Bone Miner Res 1999, 14(Suppl):S179.

    Google Scholar 

  34. LaCroix AZ, Cauley JA, Jackson R, et al.: Does statin use reduce risk of fracture in postmenopausal women? Results from the Women’s Health Initiative Observational Study [abstract]. J Bone Miner Res 2000, 15(Suppl 1):S155.

    Google Scholar 

  35. Reid IR, Hague W: Effect of pravastatin on fracture incidence in the Lipid Study: a randomized controlled trial [abstract]. J Bone Miner Res 2000, 15(Suppl 1):S225.

    Google Scholar 

  36. El-Sohemy A: Statin drugs and the risk of fracture [letter]. JAMA 2000, 284:1921.

    Article  PubMed  CAS  Google Scholar 

  37. Pedersen TR, Kjekshus J: Statin drugs and the risk of fracture [letter]. JAMA 2000, 284:1921–1922.

    Article  PubMed  CAS  Google Scholar 

  38. Edwards CJ, Hart DJ, Spector TD: Oral statins and increased bone-mineral density in postmenopausal women. Lancet 2000, 355:2218–2219.

    Article  PubMed  CAS  Google Scholar 

  39. Cauley JA, Jackson R, Pettinger M, et al.: Statin use and bone mineral density (BMD) in older women: the Women’s Health Initiative Observational Study [abstract]. J Bone Miner Res 2000, 15(Suppl 1):S155.

    Google Scholar 

  40. Chung YS, Lee MD, Lee SK, et al.: HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients. J Clin Endocrinol Metab 2000, 85:1137–1142.

    Article  PubMed  CAS  Google Scholar 

  41. Bjarnason NH, Shalmi M, Riis BJ, Christiansen C: No clinically relevant effect of fluvastatin on postmenopausal bone remodeling [abstract]. J Bone Miner Res 2000, 15(Suppl 1):S427.

    Google Scholar 

  42. Watanabe S, Fukumoto S, Takeuchi Y, et al.: Effects of one year treatment with statins on bone mass and metabolism [abstract]. J Bone Miner Res 2000, 15(Suppl 1):S194.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herrington, D.M., Klein, K.P. Statins, hormones, and women: Benefits and drawbacks for atherosclerosis and osteoporosis. Curr Atheroscler Rep 3, 35–42 (2001). https://doi.org/10.1007/s11883-001-0008-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-001-0008-9

Keywords

Navigation