Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components

Lancet. 1995 Dec 16;346(8990):1589-93. doi: 10.1016/s0140-6736(95)91928-7.


Concern about the risks of cardiovascular illness in women using combined oral contraceptives (OC) containing the progestagens desogestrel and gestodene prompted two studies of data from the UK General Practice Research Database. We compared the risks of certain cardiovascular illnesses in otherwise healthy women exposed to one of three OCs containing < 35 micrograms oestrogen plus levonorgestrel, desogestrel, or gestodene. In the first study, based on some 470 general practices, there were 15 cases of unexpected idiopathic cardiovascular death among 303,470 women who were current users of one of the study OCs. The estimated incidence rates were 8/184,536 (4.3 per 100,000) woman-years at risk for users of combined OCs containing levonorgestrel, 2/135,567 (1.5 per 100,000) for desogestrel users, and 5/105,201 (4.8 per 100,000) for gestodene users. The relative risk (RR) estimates were 0.4 (95% CI 0.1-2.1) and 1.4 (CI 0.5-4.5) for desogestrel and gestodene, respectively, compared with levonorgestrel. In the second study, derived from some 370 general practices, there were 80 cases of nonfatal venous thromboembolism (VTE) in a cohort of 238,130 otherwise healthy women. The incidence rates of VTE per 100,000 woman-years at risk were 16.1 for levonorgestrel users, 29.3 for desogestrel, and 28.1 for gestodene. The adjusted RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. In a nested case-control analysis the adjusted matched RR estimates were 2.2 (1.1-4.4) and 2.1 (1.0-4.4) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. The excess risk for nonfatal VTE associated with the new generation of combined OCs containing low-dose oestrogen and the progestagens desogestrel or gestodene compared with levonorgestrel is estimated to be 16 per 100,000 woman-years.

PIP: In two separate studies, researchers analyzed data from the UK General Practice Research Database to compare the cardiovascular risks in healthy women using one of three oral contraceptives (OCs) containing less than 35 mcg estrogen and levonorgestrel, desogestrel, or gestodene. The first study examined unexpected idiopathic cardiovascular deaths; 15 such deaths occurred. The mortality incidence rates were 4.3/100,000 for levonorgestrel OCs, 1.5/100,000 for desogestrel OCs, and 4.8/100,000 for gestodene OCs. When compared with levonorgestrel OCs (the older generation OCs), the relative risk adjusted (ARR) for age and calendar period was 0.4 for desogestrel OCs and 1.4 for gestodene OCs. The second study (cohort and case control analyses) looked at nonfatal venous thromboembolism (VTE). The crude incidence rate for nonfatal VTE was 16.1 for levonorgestrel OCs, 29.3 for desogestrel OCs, and 28.1 for gestodene OCs. When compared with levonorgestrel OCs, the ARR was 1.9 for desogestrel OCs and 1.8 for gestodene OCs. The case control analysis found that use of desogestrel OCs and gestodene OCs increased the risk of developing nonfatal VTE (all cases and controls, ARR = 2.2 and 2.1, respectively). The researchers estimated the excess risk for nonfatal VTE linked to the new generation of OCs to be 16/100,000 woman-years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality*
  • Case-Control Studies
  • Cohort Studies
  • Contraceptives, Oral, Combined / adverse effects*
  • Desogestrel / adverse effects
  • Ethinyl Estradiol / administration & dosage
  • Female
  • Humans
  • Incidence
  • Levonorgestrel / adverse effects
  • Norpregnenes / adverse effects
  • Progestins / adverse effects*
  • Risk Factors
  • Thromboembolism / chemically induced*
  • Thromboembolism / epidemiology


  • Contraceptives, Oral, Combined
  • Norpregnenes
  • Progestins
  • Gestodene
  • Ethinyl Estradiol
  • Levonorgestrel
  • Desogestrel