Treatment and Role of Hormone Replacement Therapy Chung-Ang University Hospital Chee Jeong Kim
7.2 5.3 6.4 5.6 7.3 5.5 1 1 2 3 4 10 11 7 34 49 122 123 1.0
- - 10. 2001
1998
1998
Improvement of postmenopausal symptoms Prevention of osteoporosis Prevention of cardiovascular diseases (?)
HRT and CHD in Observational Studies -Summary of 23 Studies- Non-user User RR No of patients 1677 593 CVD death 44 6 Age-adjusted rate (10000) 38.1 13.1 0.34 Adjusted for age, SBP, smoking 0.37 Education < High school 39.6 14.1 High school 37.0 16.5 > High school 23.5 8.9 Obstet Gynecol 1988;72:23S
Effect of HRT on Lipid * * * * * * Kim CJ Arch Intern Med 1996;156:1693
Proposed Mechanisms of ERT for Cardioprotective Effect Modification of lipid profiles Reduction of LDL-C and lipoprotein(a) Elevation of HDL-C Improving vasoreactivity Antioxidant Thrombotic & Fibrinolytic mechanism Changes in smooth muscle cell and matrix Angiogenesis
2763 postmenopausal women with CHD < 80 years 0.625 mg of CEE plus 2.5 mg of MPA, Follow-up averaged 4.1 years JAMA. 1998;280:605-613
Hypotheses for the HERS Results Inadequate duration of follow-up Subjects who were too old Adverse effect of progesterone
HRT and Coronary Events -HERS II- Grady G. JAMA 2002;289:49
Effect of Statin CAD Events -HERS- Herrington G. Circulation 2002;105:2962
AHA Recommendations We said that hormone treatment should not be used to try to prevent a second heart attack or death among women with established heart disease. We ll incorporate the latest findings from the WHI study into our recommendations for women who have no signs of heart disease.
WHI- JAMA 2002;288:321-333
Absolute Risk of HRT -WHI- 40 30 Events* 20 10 0 MI Stroke PTE Breat CA Colon CA *: Number of events / 10000 women-year Hip Fx JAMA 2002;288:321-333
RCTs on HRT Women s Atherosclerosis Vitamin/Estrogen Trial (WAVE) - no effect Women s Lipid Lowering Heart Atherosclerosis Trial (WELLHART) - no effect
WHI-Estrogen Arm 0 2 4 6 8 Years 0 2 4 6 8 Years JAMA. 2004;291:1701-1712
Framingham Study Estrogen Use No Total Death CHD Acutal Expected Acutal Expected < 1 year 120 7 7.1 11 6.5 > 1 year 178 10 10.5 15 9.6 6 year follow up Ann Intern Med.1978;89:157
Discrepancy between Observational Studies and RCTs HRT user in observational studies Healthy More educated Wealthy
HRT and CHD in Observational Studies -Meta-analysis of 22 Studies- JAMA 2002;288:872-881
HRT and CHD in Observational Studies -Meta-analysis of 23 Studies- Ann Intern Med. 2002;137:273-284.
1998
1 2 3 4 5 6 Overweight and Effect of HRT on Lipid Profiles Percent Change(%) 20 0-20 -40 * * * * Control Overweight TC HDL-C LDL-C VLDL-C TG Lp(a)
Effect of HRT on Inflammation Author Hormones Study Type CRP(mg/L) p value Control Drug Ridker(1999) HRT CS 0.14 0.27 <0.001 Cushman(1999) HRT CS 0.22 0.24 NS ERT CS 0.22 0.35 <0.001 Cushman(1999) HRT RCT 0.13 0.25 <0.001 (PEPI) ERT RCT 0.13 0.19 <0.001
Multiple Outcomes of Raloxifene Evaluation (MORE) 7705 osteoporotic postmenopausal women Selective ER modulator, Raloxifene 60 mg or 120 mg Follow-up averaged 48 months JAMA 2002;287:847
AHA Recommendations Selective estrogen receptor modulators (SERMs) aren t the same as HRT. However, like HRT, these should not be used for this purpose until more research is available.
Guidelines for CVD Prevention in Women -AHA- Hormone therapy Combined estrogen plus progestin hormone therapy should not be initiated to prevent CVD in postmenopausal women. (Class III, Level A) Combined estrogen plus progestin hormone therapy should not be continued to prevent CVD in postmenopausal women. (Class III, Level C) Other forms of menopausal hormone therapy (eg, unopposed estrogen) should not be initiated or continued to prevent CVD in postmenopausal women pending the results of ongoing trials. (Class III, Level C) Circulation. 2004;109:672 693
Future Direction for HRT New female sex hormones Lower dose Early administration of hormones Route of entry
Effect of Statin CAD Events -HERS- Herrington G. Circulation 2002;105:2962
1998