Conjugated equine estrogen, esterified estrogen, prothrombotic variants, and the risk of venous thrombosis in postmenopausal women.
BACKGROUND
Joint exposure to oral conjugated equine estrogen (CEE) and prothrombotic genetic variants factor II G20210A or factor V G1601A (Leiden) increase venous thrombotic risk 6- to 16-fold in postmenopausal women. Esterified estrogen (EE), an alternative estrogenic compound, appears not to be associated with increased risk and nothing is known about the joint risk with prothrombotic genetic variants.


RESULTS
We conducted a population-based, case-control study among postmenopausal women within a health maintenance organization. Subjects included 328 cases who sustained a first venous thrombosis and 1591 controls. Current hormone use was defined using electronic pharmacy records and variants FII G20210A and FV Leiden were genotyped using blood samples. FII and FV Leiden variants were associated with 2.1-fold and 3.7-fold increases in venous thrombotic risk, respectively. Overall, CEE use was associated with a 2.5-fold increase in risk compared with no hormone use, whereas EE use was not associated with a statistically increased risk. Compared with no hormone use and no variant, joint exposure to CEE and either prothrombotic variant was associated with an odds ratio (OR) of 9.1 (95% CI: 4.5 to 18.2), whereas joint exposure to EE and either variant was associated with an OR of 2.1 (0.6 to 6.8). When analyses were restricted to hormone users with either variant, CEE use was associated with an OR of 5.3 (1.3 to 21.7) compared with EE use.


CONCLUSIONS
These findings need replication and suggest EE use is associated with less risk than CEE use especially among 5% to 10% of women who are carriers of a prothrombotic variant.
Smith
Nicholas L
NL
Department of Epidemiology, University of Washington, Seattle, WA, USA. nlsmith@u.washington.edu
Heckbert
Susan R
SR
Lemaitre
Rozenn N
RN
Reiner
Alexander P
AP
Lumley
Thomas
T
Rosendaal
Frits R
FR
Psaty
Bruce M
BM
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D042724:Estrogens, Esterified (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005165:Factor V / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause / Q000378:metabolism / Q000502:physiology*; D011516:Prothrombin / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000209:etiology* / Q000503:physiopathology
D004966:Estrogens, Conjugated (USP); D042724:Estrogens, Esterified (USP); C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin