Rdt. Farmer et al., Oral contraceptives and venous thromboembolic disease. Analyses of the UK General Practice Research Database and the UK MediPlus Database, HUM REP UPD, 5(6), 1999, pp. 688-706
The results of three independent studies of venous thromboembolic disease (
VTE) and oral contraceptives are reviewed together with two further cohort/
case-control studies which we Conducted using the MediPlus and General Prac
tice Research Database (GPRD) databases. These latter studies jointly invol
ved 395 cases and uniquely examined the association between VTE and individ
ual combined oral contraceptive (COC) formulations. The two studies yielded
very similar results. Crude incidence rates for idiopathic VTE of 4.6 and
3.8 were found per 10 000 exposed woman-years (EWY), in the MediPlus and GP
RD studies respectively Incidence rates increased markedly with age, and in
both databases the rates amongst users of levonorgestrel products were low
er than those amongst users of desogestrel and gestodene products, ii case
fatality rate of 3% and a mortality rate of 10 per million EWY were estimat
ed. Odds ratios (OR) mere calculated for confounding variables and differen
t COC formulations. Both database studies indicated an excess of current sm
okers and women with high body mass indites amongst cases. There mere signi
ficantly more cases with asthma in the GPRD study and cases who had been us
ing their COC for less than a year. No statistically significant difference
s between COC formulations were found in the analyses where controls were m
atched to cases by practice and year of birth in both the MediPlus and GPRD
studies. In the GPRD study we also ran a study where controls were matched
by practice and within 5 year age bands. In this study the OR were consist
ently higher for the newer or 'third generation' products than when control
s were matched by year of birth. However only the acne formulation/OC conta
ining cyproterone acetate and 35 mu g ethinyloestradiol yielded a significa
nt OR of 2.3. It may be concluded that improvements in prescribing are para
mount as the results strongly indicate that overweight women and those who
smoke are at a greater risk of VTE, Further study is required to elucidate
the possibility that asthma or its treatment may predispose to VTE, alone o
r in combination with other risk factors. However, neither the MediPlus nor
GPRD studies indicate that any one COC formulation poses a greater risk of
VTE than another.