Oral contraceptives and thromboembolism

The CSM have provided evidence that the risk of venous thromboembolism associated with oral contraceptives containing norethisterone, levonorgestrel or ethynodiol increases the risk (excess risk) of venous thromboembolism by around 10 to 15 cases per 100,000 women per annum. However these studies showed that combined oral contraceptives containing desogestrel and gestodene are associated with an approximate two-fold increase in the risk, compared with those containing other progestogens.

Insufficient data was available to know whether there was an increased risk associated with combined preparations containing norgestimate.

The National Prescribing Centre have stated that (1):

• all COCs increase the risk of venous thromboembolism (VTE). There is a small excess risk associated with COCs containing desogestrel or gestodene (1,2)
  • however, in absolute terms, the risk is still low and is lower than the risk of VTE in pregnancy
• on a population level, it would seem sensible to prescribe COCs that do not contain desogestrel or gestodene first-line. However, on an individual level, providing women are fully informed of the risks and do not have medical contraindications, it should be a matter of clinical judgement and personal choice as to which type of oral contraceptive is prescribed
• all COCs should be prescribed with caution to women with a higher baseline risk of VTE
• the riisk of VTE associated with COC use and non-use is detailed in the table below:

VTE risk with concomitant use of hormonal contraception and non-steroidal anti-inflammatory drug (NSAID)

A large Danish cohort study concluded (3):

• NSAID use was positively associated with the development of venous thromboembolism in women of reproductive age
  • number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception
    • in the study definitions of risk of hormonal contraception were:
      • high risk hormonal contraceptives
        • included combined oestrogen and progestin patch, vaginal ring, and tablets containing 50 µg ethinyl oestradiol, or the progestins desogestrel, gestodene, drospirenone, or the anti-androgen cyproterone
      • medium risk hormonal contraception included all other combined oral contraceptives as well as the medroxyprogesterone injection.
      • low risk/no risk hormonal contraceptives were considered as progestin-only tablets, implants, and hormone intrauterine devices
    • numbers of extra venous thromboembolic events per 100 000 women over the first week of NSAID treatment compared with non-use of NSAIDs were:
      • 4 (3 to 5) in women not using hormonal contraception,
      • 23 (19 to 27) in women using high risk hormonal contraception,
      • 11 (7 to 15) in those using medium risk hormonal contraception, and
      • 3 (0 to 5) in users of low/no risk hormonal contraception
  • women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly

Reference:

1. MeReC Bulletin (2006); 17(2):1.
2. Waller P (1995). Venous thromboembolism and oral contraceptives that contain desogestrel or gestodene. CMO's Update; 8: 2.
3. Meaidi A, Mascolo A, Sessa M, Toft-Petersen A P, Skals R, Gerds T A et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort studyBMJ 2023; 382 :e074450