Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. The Heart and Estrogen/progestin Replacement Study.
BACKGROUND
Animal and observational epidemiologic studies have reported that estrogens may increase the risk for gallstones. No major clinical trials have examined the effect of estrogen plus progestin therapy in postmenopausal women on the risk for biliary tract surgery.


OBJECTIVE
To determine the effect of estrogen plus progestin on the risk for biliary tract surgery in postmenopausal women with known coronary artery disease.


METHODS
Randomized, double-blind placebo-controlled trial of postmenopausal hormone therapy for coronary heart disease.


METHODS
20 U.S. clinical centers.


METHODS
2253 postmenopausal women with a gallbladder, 44 to 79 years of age at baseline, in the Heart and Estrogen/progestin Replacement Study (HERS).


METHODS
Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, daily in one tablet or identical placebo.


METHODS
Documented biliary tract surgery.


RESULTS
A total of 147 women (7%) were hospitalized for biliary tract surgery in HERS. Treatment with estrogen plus progestin resulted in a marginally significant 38% increase in the relative risk for biliary tract surgery (P = 0.05). A small absolute difference in risk suggested that for every 185 women treated with estrogen plus progestin, one additional woman had biliary tract surgery per year. After adjustment for baseline and in-study statin use, the association was attenuated further (P = 0.09). After adjustment for treatment assignment and other variables, increased body mass index, fibric acid use, and a history of nonsurgical gallbladder disease were associated with an increased risk for biliary tract surgery, whereas statin use was associated with a decreased risk (for each comparison, P < 0.05).


CONCLUSIONS
Estrogen plus progestin therapy among postmenopausal women with known coronary disease resulted in a marginally significant increase in the risk for biliary tract surgery.
Simon
J A
JA
General Internal Medicine Section (111A1), Medical Service, Veterans Affairs Medical Center, San Francisco, CA 94121, USA. jasimon@itsa.ucsf.edu
Hunninghake
D B
DB
Agarwal
S K
SK
Lin
F
F
Cauley
J A
JA
Ireland
C C
CC
Pickar
J H
JH
D000328:Adult; D000368:Aged; D002769:Cholelithiasis / Q000209:etiology* / Q000601:surgery*; D003327:Coronary Disease / Q000150:complications* / Q000517:prevention & control; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011372:Progestins / Q000009:adverse effects*; D012307:Risk Factors
D004967:Estrogens; D011372:Progestins