Oral contraceptives still linked to increased venous thrombosis risk

Findings from two studies from Denmark and the Netherlands demonstrated an association between oral contraceptives — including type, regimen and duration — and increased risk for venous thrombosis, confirming findings from previous studies.

In the first study, researchers from Copenhagen, Denmark, assessed VTE risk in Danish women aged 15 to 49 years. They studied data from 3.4 million woman years of current use, 2.3 million woman years of former use and 4.8 million woman years of never use.

There were 4,213 first-time thrombotic events; 2,045 occurred in women currently using hormonal contraception. Events included 61.8% deep vein leg thrombosis, 26.2% pulmonary embolism, 4.7% femoral vein thrombosis, 1.2% portal thrombosis, 0.8% caval or renal thrombosis and 5.4% unspecified deep vein thrombosis.

The crude incidence of venous thromboembolism was 6.29 per 10,000 woman years for oral contraceptive users vs. 3.01 per 10,000 woman years among non-users, which included never or former users.

Results of the study indicated that women who have just started using oral contraceptives have a higher risk than those who have used it for some time. During the first year of use, the adjusted rate ratio was 4.17 (95% CI, 3.73-4.66); whereas, the risk was reduced to a rate of 2.76 (95% CI, 2.53-3.02) after more than four years of use.

When compared with users of oral contraceptives containing levonorgestrel and after adjustment for duration and same dose of oestrogen, the rate for VTE was 0.98 (95% CI, 0.71-1.37) for oral contraceptives containing norethisterone, 1.19 (95% CI, 0.96-1.47) for those containing norgestimate and 1.88 (95% CI, 1.47-2.42) for those with cyproterone. Risk was also significantly higher with oral contraceptives containing desogestrel (1.82; 95% CI, 1.49-2.22), gestodene (1.86; 95% CI, 1.59-2.18) and drospirenone (1.64; 95% CI, 1.27-2.10).

There was no association between progestogen only pills and hormone releasing intrauterine devices and risk for venous thrombosis.

“For women of normal weight and without known genetic predispositions, we recommend a low dose combined pill as first choice for contraception,” the researchers wrote. “For women genetically predisposed to venous thrombosis, however, a progestogen only pill or hormone releasing intrauterine device seems to be the appropriate first choice.”

MEGA study

In the second study, researchers analyzed data from patients (n=1,524) and a control group (n=1,760) aged 18 to 50 years from six anticoagulation clinics in the Netherlands from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study.

There was a fivefold increase of the risk of venous thrombosis associated with currently available oral contraceptives, according to the findings of the MEGA study.

The overall risk increase (odds ratio) for VTE was 5.0 for those currently using oral contraceptives. When compared with non-use, the OR for oral contraceptives containing levonorgestrel was 3.6, and was even higher for contraceptives containing gestodene (OR=5.6), desogestrel (OR=7.3), cyproterone acetate (OR=6.8) and drospirenone (OR=6.3).

When compared with contraceptives containing levonorgestrel, those with gestodene (OR=1.6), desogestrel (OR=2.0), cyproterone (OR=2.0) and drospirenone (OR=1.7) were prone to higher risk for venous thrombosis.

Thrombotic risk was lower with a 20 mcg dose of estrogen (OR=0.8; 95% CI, 0.5-1.2) than with a 50 mcg dose (OR=1.9; 95% CI, 1.1-3.4). Risk was highest during the first three months of oral contraceptive use with an OR of 12.6 (95% CI, 7.1-22.4).

“After one year, the risk for venous thrombosis for oral contraceptive users compared with non-users decreased to the overall estimate of a fivefold increased risk,” the researchers wrote.

The smallest increase of adverse events will affect many because a large number of women use oral contraceptives, according to researchers.

“Our results clearly show that the safest option with regard to the risk for venous thrombosis is an oral contraceptive containing levonorgestrel combined with a low dose of estrogen,” they said.

Lidegaard O. BMJ. 2009;doi:10.1136/bmj.b2890.

van Hylckama Vlieg A. BMJ. 2009;doi:10.1136/bmj.b2921.