The cohort and case-control subjects used in this study have been reported previously. The objective of our study was to assess the risk of stroke associated with oral and transdermal routes of administration of HRT in a cohort of postmenopausal women using a nested case-control analysis. 7 Thus different routes of administration of HRT may be associated with a different risk of cerebrovascular events in postmenopausal women. 6 Several studies suggest that the transdermal route exerts a different impact on biological cardiovascular risk markers by avoidance of the first pass effect in the liver. Transdermal oestrogen preparations are effective in the treatment of postmenopausal symptoms 5 in a manner similar to oral oestrogens. One observational study suggested a lower risk of transient ischaemic attack with transdermal oestrogen use compared with oral oestrogen, but the risk of stroke could not be estimated because of the small number of cases. 1 2 3 However, these clinical trials evaluated oral HRT and did not explore other routes of administration. This was confirmed in recent meta-analyses showing a 30% increased risk of stroke, identical for oestrogens alone or in combination with progestogen. In particular, several clinical trials have shown an increased risk of stroke associated with HRT in postmenopausal women. Although many observational studies have suggested a protective effect against cardiovascular disease, this has been challenged by the results of randomised controlled trials. Hormone replacement therapy (HRT), especially oestrogen alone or in combination with progestogen, is used for the relief of climacteric symptoms in postmenopausal women.
The presence of residual confounding, however, cannot be entirely excluded in the interpretation of this finding.
Current users of oral HRT had a higher rate of stroke than non-users (rate ratio 1.28 (1.15 to 1.42)) with both low dose and high dose.Ĭonclusions The use of transdermal HRT containing low doses of oestrogen does not seem to increase the risk of stroke. The risk of stroke was not increased with use of low oestrogen dose patches (rate ratio 0.81(0.62 to 1.05)) compared with no use, whereas the risk was increased with high dose patches (rate ratio 1.89 (1.15 to 3.11)). The adjusted rate ratio of stroke associated with current use of transdermal HRT was 0.95 (95% CI 0.75 to 1.20) relative to no use. Results There were 15 710 cases of stroke matched to 59 958 controls. Current use was considered as a prescription whose duration included the index date. Main outcome measures Rate ratio of stroke associated with current use of oral and transdermal HRT compared with no use. Oestrogens were further subdivided according to the route of administration (oral v transdermal) and dose (high v low).
ANTI STROKE ADD ON FOR HRT LUPRON PLUS
Exposure to hormone replacement therapy (HRT) was categorised into oestrogens only, oestrogens plus progestogen, progestogen only, and tibolone. For each case of stroke occurring during follow-up, up to four controls were selected from among the cohort members in the risk sets defined by the case. Participants Cohort of all women in the database aged 50-79 years between 1 January 1987 and 31 October 2006 who were members of a practice that fulfilled predefined quality criteria and without a diagnosis of stroke before cohort entry. Setting About 400 general practices in the United Kingdom contributing to the General Practice Research Database. Objectives To determine the risk of stroke associated with oral and transdermal routes of administration of hormone replacement therapy.ĭesign Population based nested case-control study.