Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives.
OBJECTIVE
To assess the relationship between venous thromboembolic disease (VTE) and use of low-estrogen dose (<50 microg) combined estrogen-progestin oral contraceptives (OC) and three thrombosis-related gene mutations in a United States population.


METHODS
This case-control study was conducted in 1998-2000 among women ages 15-44 years who were members of the Kaiser Permanente Medical Care Program [KPMCP] (Northern and Southern California). Cases were women with incident VTE; about three times as many women frequency matched for age were randomly selected as controls from the KPMCP membership in the same years. Data were collected in a 1 h face-to-face interview; blood was drawn to extract DNA to test for gene polymorphisms. The analysis data set comprised 196 cases (mean age 35.3 years) and 746 controls (mean age 36.2 years).


RESULTS
The adjusted odds ratio (OR) for VTE associated with current OC use was 4.07 (95% confidence interval [CI]: 2.77-6.00). The OR associated with OC use was higher for women who were obese than in the nonobese (p = 0.01 for likelihood test for interaction) and in women without predisposing medical conditions (p = 0.02 for interaction). The adjusted OR for VTE was 7.10 (95% CI: 2.33-21.61) in women with factor V Leiden (G1691A) mutation, 2.83 (95% CI: 0.70-11.63) in women with prothrombin G20210A mutation and 0.26 (95% CI: 0.10-0.65) in women with the MTHFR C677T mutation. The OR for VTE in OC users with factor V Leiden mutation (11.32) was elevated more than in OC users without the mutation (3.20) and women with the mutation who were non-OC users (8.42), but confidence intervals overlapped.


CONCLUSIONS
The risk of VTE is increased in users of low-estrogen OC formulations. Obese women appear to be at greater risk of VTE when using OCs.
Sidney
Stephen
S
Division of Research, Kaiser Permanente Medical Care Program (Northern California), 2000 Broadway, Oakland 94612, USA. sxs@dor.kaiser.org
Petitti
Diana B
DB
Soff
Gerald A
GA
Cundiff
Deborah L
DL
Tolan
Kimberly K
KK
Quesenberry
Charles P
CP
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016001:Confidence Intervals; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects* / Q000737:chemistry; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007407:Interviews as Topic; D009154:Mutation; D009765:Obesity / Q000150:complications; D016017:Odds Ratio; D011372:Progestins / Q000008:administration & dosage; D011516:Prothrombin / Q000378:metabolism; D012307:Risk Factors; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000235:genetics*
D003277:Contraceptives, Oral, Combined; D004967:Estrogens; D011372:Progestins; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin