Estrogen plus progestin and the risk of coronary heart disease.
BACKGROUND
Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI).


METHODS
The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD).


RESULTS
After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD.


CONCLUSIONS
Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.
Manson
JoAnn E
JE
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA. jmanson@rics.bwh.harvard.edu
Hsia
Judith
J
Johnson
Karen C
KC
Rossouw
Jacques E
JE
Assaf
Annlouise R
AR
Lasser
Norman L
NL
Trevisan
Maurizio
M
Black
Henry R
HR
Heckbert
Susan R
SR
Detrano
Robert
R
Strickland
Ora L
OL
Wong
Nathan D
ND
Crouse
John R
JR
Stein
Evan
E
Cushman
Mary
M
D000368:Aged; D016022:Case-Control Studies; D003327:Coronary Disease / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D004311:Double-Blind Method; D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced / Q000453:epidemiology; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D017698:Postmenopause; D045167:Progesterone Congeners / Q000009:adverse effects* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); C466383:Prempro; D045167:Progesterone Congeners; D017258:Medroxyprogesterone Acetate