NEW YORK (Reuters Health) – The risk of venous thromboembolism (VTE) conferred by oral contraceptives appears to be lowest with the older standbys: contraceptives containing levonorgestrel, progestogen-only pills, and hormone-releasing intrauterine devices.

These findings are according to two European studies in this week’s issue of BMJ Online First.

The authors of the first study note that as doses of estrogen in oral contraceptives were reduced and newer products were introduced, research lagged behind, so that information is sparse on the risk of venous thromboembolism associated with each agent.

Dr. Ojvind Lidegaard and colleagues at Copenhagen University, Denmark studied data from 1995-2005 from four national Danish registries.

In 10.4 million woman-years of observation, 4213 first time venous thrombotic events occurred, including 2045 among current users of oral contraception. The crude incidence of VTE was doubled among current users of oral contraceptives compared with never or former users (6.29 vs 3.01 per 10,000 woman-years).

However, the risk was highest during the first year of use, dropping substantially from an adjusted rate ratio of 4.17 to 2.76 after 4 years of use. The risk also declined with decreasing dose of estrogen.

“For the same dose of estrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel,” Dr. Lidegaard write. Furthermore, progestogen-only pills and hormone releasing IUDs were not linked with any increased VTE risk.

The absolute risk of venous thrombosis with any type of combined oral contraceptive in young women is less than one in 1000 user years, the report indicates.

For overweight and obese women, and those genetically predisposed to venous thrombosis, the lower risk preparations should be first choice, the researchers say.

They point out that if the risk of arterial diseases were the same for the new progestogens as for levonorgestrel, then about 7400 women would have to change from the newer products to oral contraceptives containing levonorgestrel to prevent one case of venous thrombosis.

Results were similar in the second study, by investigators at Leiden University, the Netherlands.

Headed by Dr. F. R. Rosendaal, the study involved premenopausal women less than 50 years old (1524 patients with deep venous thrombosis of the leg or arm and/or pulmonary embolism, and 1760 controls).

“The risk of thrombosis associated with oral contraceptives containing cyproterone acetate or drospirenone was similar to that associated with oral contraceptives containing desogestrel; a sixfold to sevenfold increased risk compared with non-users,” Dr. Rosendaal’s team reports.

They found that an oral contraceptive containing levonorgestrel combined with a low dose of estrogen was “the safest option,” least likely to cause venous thrombosis.

Reference:
BMJ 2009;339:h2890,h2921.