Venous thrombosis and conjugated equine estrogen in women without a uterus.
BACKGROUND
Postmenopausal hormone therapy has been associated with a 2- to 3-fold increased risk of venous thromboembolism (VT) (including deep vein thrombosis and pulmonary embolism) in observational studies and secondary prevention clinical trials. Clinical trial data on the effects of estrogen alone on VT are limited.


METHODS
The Women's Health Initiative estrogen trial enrolled 10 739 women aged 50 to 79 years without a uterus. Participants were randomly assigned to receive conjugated equine estrogen (0.625 mg/d) or placebo.


RESULTS
During a mean of 7.1 years, VT occurred in 111 women randomly assigned to receive estrogen (3.0 per 1000 person-years) and 86 randomly assigned to receive placebo (2.2 per 1000 person-years; hazard ratio, 1.32; 95% confidence interval, 0.99-1.75). Deep venous thrombosis was reported in 85 women randomly assigned to receive estrogen (2.3 per 1000 person-years) and 59 randomly assigned to receive placebo (1.5 per 1000 person-years; hazard ratio, 1.47; 95% confidence interval, 1.06-2.06). The VT risk was highest in the first 2 years. There were no significant interactions between estrogen use and age, body mass index, or most other VT risk factors. Comparison of Women's Health Initiative VT findings for estrogen and previous Women's Health Initiative findings for estrogen plus progestin showed that the hazard ratios for estrogen plus progestin were significantly higher than those for estrogen alone (P = .03), even after adjusting for VT risk factors.


CONCLUSIONS
An early increased VT risk is associated with use of estrogen, especially within the first 2 years, but this risk increase is less than that for estrogen plus progestin.
Curb
J David
JD
University of Hawaii and Pacific Health Research Institute, Honolulu, USA.
Prentice
Ross L
RL
Bray
Paul F
PF
Langer
Robert D
RD
Van Horn
Linda
L
Barnabei
Vanessa M
VM
Bloch
Michael J
MJ
Cyr
Michele G
MG
Gass
Margery
M
Lepine
Lisa
L
Rodabough
Rebecca J
RJ
Sidney
Stephen
S
Uwaifo
Gabriel I
GI
Rosendaal
Frits R
FR
D000368:Aged; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016016:Proportional Hazards Models; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D020246:Venous Thrombosis / Q000139:chemically induced / Q000453:epidemiology*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004966:Estrogens, Conjugated (USP)