Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel.
BACKGROUND
Previous studies have reported that users of the "third-generation" oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of norgestimate-containing OCs compared to other OCs, however, are lacking.


OBJECTIVE
The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel.


METHODS
Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing norgestimate with 35 microg of ethinyl estradiol (EE), desogestrel with 30 microg of EE or levonorgestrel with 30 microg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs.


RESULTS
Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8-1.6] and 1.7 (95% CI, 1.1-2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5-36.5), 53.5 (95% CI, 42.9-66.0) and 27.1 (95% CI, 21.1-34.3) per 100,000 woman-years for users of norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8-1.5) and 2.0 (95% CI, 1.4-2.7), respectively.


CONCLUSIONS
The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.
Jick
Susan S
SS
Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, MA 02421, USA. sjick@bu.edu
Kaye
James A
JA
Russmann
Stefan
S
Jick
Hershel
H
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects*; D016208:Databases, Factual; D017135:Desogestrel / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects*; D008137:Longitudinal Studies; D009644:Norgestrel / Q000009:adverse effects / Q000031:analogs & derivatives*; D016017:Odds Ratio; D012307:Risk Factors; D013923:Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology
D003277:Contraceptives, Oral, Combined; D003280:Contraceptives, Oral, Synthetic; D009644:Norgestrel; D016912:Levonorgestrel; D017135:Desogestrel; C017576:norgestimate