Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years - Relationships to hormone replacement therapy

Hormone replacement therapy (HRT) has been shown to increase the relative risk of idiopathic venous thromboembolism (VTE) about threefold in several observational studies and one randomised controlled trial. Whether or not this relative risk is higher in women with underlying thrombophilia phenotypes, such as activated protein C (APC) resistance, is unknown. We therefore restudied the participants in a case-control study of the relationship between the use of HRT and the occurrence of idiopathic VTE in women aged 45-64 years. After protocol exclusions, 66 of the cases in the original study and 163 of the controls were studied. Twenty haematological variables relevant to risk of VTE were analysed, including thrombotic states defined from the literature. The relative risk of VTE showed significant associations with APC resistance (OR 4.06; 95% CI 1.62, 10.21); low antithrombin (3.33; 1.15, 9.65) or protein C (2.93; 1.06, 8.14); and high coagulation factor IX (2.34: 1.26, 1.35), or fibrin D-dimer (3.84; 1.99, 7.32). HRT use increased the risk of VTE in women without any of these thrombotic static; (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE was also found in women with prothrombotic states. Thus for example, the combination of HRT use and APC resistance increased the risk of VTE about 13-fold compared with women of similar age without either APC resistance or HRT use (OR 13.27; 95%, CI 4.30, 40.97). We conclude that the combination of HRT use and thrombophilias (especially if multiple) increases the relative risk of VTE substantially; hence women known to have thrombophilias (especially if multiple) should be counselled about this increased risk prior to prescription of HRT. However. HRT increases the risk of VTE about fourfold even in women without any thrombotic abnormalities: possible causes are discussed

Oral contraceptives and cervical cancer--further findings from the Oxford Family Planning Association contraceptive study.

In 1983, we reported results from the Oxford Family Planning Association contraceptive study regarding the association between oral contraceptives (OCs) and cervical neoplasia, after a 10 year follow-up of a cohort of 17,000 women. Further findings from this study are reported here after an additional 12 years of follow-up. A nested case--control design was used in which cases were all women diagnosed under 45 years of age with invasive carcinoma (n = 33), carcinoma in situ (n = 121) or dysplasia (n = 159). Controls were randomly selected from among cohort members and matched to cases on exact year of birth and clinic attended at recruitment to study. Conditional logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) associated with various aspects of OC use relative to never users adjusted for social class, smoking, age at first birth and ever use of diaphragm or condom. Ever users of OCs had a slightly elevated OR for all types of cervical neoplasia combined (OR = 1.40, 95% CI 1.00-1.96). Odds ratios were highest for invasive carcinoma (OR = 4.44, 95% CI 1.04-31.6), intermediate for carcinoma in situ (OR = 1.73, 95% CI 1.00-3.00) and lowest for dysplasia (OR = 1.07, 95% CI 0.69-1.66). The elevated risk associated with OC use appeared to be largely confined to current or recent (last use in the past 2 years) long-term users of OCs. Among current or recent users, ORs for all types of cervical neoplasia combined were 3.34 (95% CI 1.96-5.67) for 49-72 months of use, 1.69 (95% CI 0.97-2.95) for 73-96 months and 2.04 (95% CI 1.34-3.11) for 97 or more months. These results suggest a possible effect of OC use on later stages of cervical carcinogenesis, although residual confounding due to sexual factors or human papillomavirus (HPV) infection cannot be ruled out

Fertility in relation to the risk of breast cancer.

All studies reported here, like our own, support the view that the higher risk of breast cancer in women having a late first birth is attributable to early pregnancy itself having a direct protective effect against the disease, a benefit which they have not experienced. One study, however, has directly examined breast cancer risk in two groups of infertile women - those presumed to have 'progesterone deficiency' and those presumed to have infertility of non hormonal origin. The results suggested that breast cancer risk was increased in premenopausal women (but not in postmenopausal women) with 'progesterone deficiency'. The number of cases of premenopausal breast cancer included in the analysis (11) was, however, very small. In our view, the findings in this study do not weigh heavily against our results and those of others

Breast self examination and breast cancer stage at diagnosis.

The relationship between breast self examination (BSE) and breast cancer stage at diagnosis was examined in 616 women aged 15-59 years. Differences in tumour characteristics between those not practising BSE and those practising but not taught were small and inconstant. However, women who had both practised and had been taught BSE had more favourable tumours than the non-practising group. The difference was most marked in terms of tumour size and the involvement of axillary nodes. The proportions of women in the non-BSE and taught-BSE groups with each characteristic were respectively: size less than or equal to 2 cm 33% and 45%, T1 clinical stage 27% and 42%, and N0 pathological stage 37% and 50%. This advantage to taught-BSE women persisted after adjustment for the identified confounding factors of age, social class and oral contraceptive use. The likely impact on breast cancer mortality is difficult to assess, although the potential benefit of the lead time gained must not be ignored when assessing the costs and benefits of BSE

Early oral contraceptive use and breast cancer: results of another case-control study.

We report the results of a case-control study of oral contraceptive use and breast cancer conducted in London, Oxford and Edinburgh between 1980 and 1984. One thousand one hundred and twenty-five women aged 16-64 years with newly diagnosed breast cancer and a like number of matched controls were interviewed and asked about their past due use of oral contraceptives (OCs). Among women aged 45 years or more at diagnosis there was no evidence of an association between OC use and breast cancer. Among the 351 pairs of women aged under 45 years at diagnosis there was a significantly elevated risk associated with increasing duration of use before first full term pregnancy (relative risk for 4+ years use versus never use = 2.6, 95% confidence limits, 1.3-5.4). Since this result is at variance with the findings in some other studies we have investigated the nature of this association with particular emphasis on possible bias, pill type and a latent effect