Lidegaard, Ø., Løkkegaard, E., Svendsen, A. L., & Agger, C. (2009). Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ (Clinical Research Ed.), 339(aug13 2), b2890. https://doi.org/10.1136/bmj.b2890
Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339(aug13 2):b2890. doi:10.1136/bmj.b2890
Lidegaard, Øjvind, et al. "Hormonal contraception and risk of venous thromboembolism: national follow-up study." BMJ (Clinical Research Ed.), vol. 339, no. aug13 2, 2009, pp. b2890.
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Combined oral contraceptives were linked to higher blood clot risk
In a Danish cohort of women aged 15 to 49, current pill users had 6.29 first venous clots per 10,000 woman years against 3.01 in non-users (crude rates). At equal estrogen dose and duration, pills with desogestrel, gestodene or drospirenone were linked to higher risk than levonorgestrel pills. Progestogen-only pills and hormone-releasing intrauterine devices were not linked to higher risk.
Key Findings
Venous thrombosis occurred at 3.01 per 10,000 woman years among women not using oral contraceptives and 6.29 per 10,000 woman years among current users.
Rate ratios versus non-users of combined oral contraceptives were 4.17 (95% CI 3.73 to 4.66) under 1 year, 2.98 (2.73 to 3.26) at 1-4 years, 2.76 (2.53 to 3.02) beyond 4 years.
Desogestrel or gestodene pills with the lowest estrogen dose were associated with 18% lower venous thromboembolism risk (95% CI 7% to 27%) than those with the middle dose, adjusted for duration.
Against levonorgestrel pills at equal dose and duration, rate ratios were 1.82 (1.49 to 2.22) desogestrel, 1.86 (1.59 to 2.18) gestodene, 1.64 (1.27 to 2.10) drospirenone, 1.88 (1.47 to 2.42) cyproterone.
At equal dose and duration, norethisterone and norgestimate pills had rate ratios of 0.98 (0.71 to 1.37) and 1.19 (0.96 to 1.47) against levonorgestrel pills. The cohort had 4213 first-time events.
Interpretation
This cohort study followed women aged 15 to 49 in Denmark. Researchers linked records from four national registries. Clot risk was highest in the first year of pill use. Risk fell the longer women used the pill. The authors say this pattern supports a causal link between combined pills and venous thrombosis. They note that the higher risk seen with drospirenone pills, compared with levonorgestrel pills, needs confirmation in further studies.
RRM Context
Combined pills are suppressive medications. They stop ovulation with synthetic hormones. Restorative reproductive medicine looks past symptom control. It looks for the cause of painful, heavy or irregular cycles, and treats that cause directly.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration.
Design
National cohort study.
Setting
Denmark, 1995-2005.
Participants
Danish women aged 15-49 with no history of cardiovascular or malignant disease.
Main Outcome Measures
Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period.
Results
10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 mug desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26).
Conclusion
The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen 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. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.
