Combination OCs and VTE Risk: Nailing Down the Role of the Progestin

Robert L. Barbieri, MD reviewing Vinogradova Y et al. BMJ 2015 May 26.

Clinicians should prescribe combination OCs containing progestins with the lowest excess risk for VTE.

Combination estrogen-progestin oral contraceptives (OCs) are associated with excess risk for venous thromboembolism (VTE), but controversy persists about the relative contributions of specific progestins. These relations were analyzed using two general practice databases in the U.K. This study, the largest to date, included 10,562 VTE cases and 42,034 age-matched women without VTE. Odds ratios (ORs) were adjusted for smoking status, alcohol use, ethnic group, body-mass index, and comorbidities.

Current use of combination OCs was associated with increased risk for VTE (overall OR, 2.97; 95% confidence interval (CI), 2.78–3.17), and progestin type influenced degree of risk. The three progestins that raised VTE risk the least were:

• Levonorgestrel (OR, 2.38; 95% CI, 2.18–2.59)
• Norgestimate (OR, 2.53; 95% CI, 2.17–2.96)
• Norethindrone (OR, 2.56, 95% CI, 2.15–3.06)

Four progestins were associated with greater excess risk for VTE:

• Gestodene (OR, 3.64, 95% CI, 3.00–4.43)
• Drospirenone (OR, 4.12, 95% CI, 3.43–4.96)
• Cyproterone (OR, 4.27, 95% CI, 3.57–5.11)
• Desogestrel (OR, 4.28, 95% CI, 3.66–5.01)

By specific progestin, the numbers of extra cases of VTE yearly per 10,000 treated women were: 6 (levonorgestrel), 6 (norgestimate), 7 (norethindrone), 11 (gestodene), 13 (drospirenone), 14 (desogestrel), and 14 (cyproterone). Gestodene and cyproterone are not available for prescription in the U.S.

Citation(s):

Vinogradova Y et al. Use of combined oral contraceptives and risk of venous thromboembolism: Nested case-control studies using the QResearch and CPRD databases. BMJ 2015 May 26; 350:h2135.