Should progestins be blamed for the failure of hormone replacement therapy to reduce cardiovascular events in randomized controlled trials?
Many observational studies and experimental and animal studies have demonstrated that estrogen replacement therapy (ERT) or hormone replacement therapy (HRT) (estrogen plus progestin) significantly reduces the risk of coronary heart disease. Nonetheless, recent randomized controlled trials demonstrated some trends toward an increased risk of cardiovascular events rather than a reduction of risk. Recently, both the HRT and ERT arms of the Women's Health Initiative (WHI) study were terminated early because of an increased/no incidence of invasive breast cancer, increased incidence of stroke, and increased trend/no protective effects of cardiovascular disease. We discuss the controversial effects of HRT and ERT on cardiovascular system and provide a hypothesis that the failure of HRT and ERT in reducing the risk of cardiovascular events in postmenopausal women might be because of the stage of their atherosclerosis at the time of initiation of HRT or ERT.
Koh
Kwang Kon
KK
Division of Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-Dong, Namdong-Gu, Incheon, Korea 405-760. kwangk@ghil.com
Sakuma
Ichiro
I
D000368:Aged; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002986:Clinical Trials as Topic; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D015914:Estrogen Replacement Therapy; D005260:Female; D000882:Haplorhini; D006439:Hemodynamics / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects; D020249:Hormone Replacement Therapy; D006801:Humans; D007249:Inflammation; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D017698:Postmenopause; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011859:Radiography; D016032:Randomized Controlled Trials as Topic; D051381:Rats
D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D045167:Progesterone Congeners; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein