Venous thromboembolism and hormonal contraception

Abstract

The aim of this guidance is to present evidence-based recommendations and statements on venous thromboembolism (VTE) and hormonal contraception. the Cochrane Library (to 2003) and the US National Guideline Clearing House. Searches used relevant medical subject headings (MeSH) terms and text words. The Cochrane Library was searched for systematic reviews, meta-analyses and controlled trials. Previous guidance from the Royal College of Obstetricians and Gynaecologists (RCOG), the Faculty of Family Planning and Reproductive Health Care (FFPRHC) and the World Health Organization (WHO) was reviewed. Key publications were appraised according to standard methodological checklists before conclusions were considered as evidence.The definitions of types of evidence used in this guideline originate from the US Agency for Health Care Research and Quality.Where possible, recommendations are based on and explicitly linked to the evidence that supports them.Areas lacking evidence were designated 'good practice points.' Does combined oral contraception increase the risk of venous thromboembolism?The relative risk of venous thromboembolism is increased with combined oral contraceptive use. Nevertheless, the rarity of venous thromboembolism in women of reproductive age means that the absolute risk remains small.The term 'combined oral contraception' is used here to describe monophasic preparations containing a low dose (20-35 micrograms) of ethinyl estradiol in combination with a progestogen. Progestogens include norethisterone and levonorgestrel:'second generation'; desogestrel and gestodene:'third generation'; and the newest progestogen, drospirenone:'fourth generation'.The terms second, third or fourth generation can be confusing and will not be used further. 11 Risk of venous thromboembolismCombined oral contraceptives containing levonorgestrel or norethisterone are associated with a lower risk of venous thromboembolism than those containing desogestrel or gestodene. A levonorgestrel-or norethisterone-containing combined oral contraceptive should be advised as a pill of first choice. However, after counselling, a woman may choose a desogestrel-or gestodenecontaining combined pill.Epidemiological studies show a three-to five-fold increase in the risk of VTE with COC use, which does not appear to be related to the dose of ethinyl oestradiol (when less than 50 micrograms is used) but to the type of progestogen. 12,13 Meta-analyses provide further support for this increased risk. 4,14 COCs containing gestodene or desogestrel are associated with an almost two-fold increase in the risk of VTE compared with COCs containing norethisterone or levonorgestrel (adjusted OR 1.7, 95% CI 1.4-2.0). 4 The apparent relationship between progestogen type and risk of VTE 3 may be due to confounding or bias, inherent in observational studies. 15,16 However, this increased risk has biological plausibility (section 4.8). 17The relative risk of venous thromboembolism increases in the first 4 months after starting combined oral contraception. This ris...