Endocrine Abstracts

The hormone oestrogen is reported to be the most widely prescribed drug worldwide through its use in the contraceptive pill and in hormone replacement therapy (HRT). Oestrogen and HRT has been widely prescribed for prevention of osteoporosis and relief of menopausal symptoms. However, as women age, their risk of stroke and heart disease also increases, particularly after the menopause. The effects of oestrogen on stroke risk and on the ischaemic brain are complex and still not fully understood. Early observational studies of HRT in postmenopausal women suggested therapy was associated with a reduced risk of cardiovascular and cerebrovascular disease. However, this has not been confirmed in more recent large scale randomised, placebo-controlled trials (e.g. The Women's Estrogen in Stroke Trial (WEST), Heart and Estrogen/Progestin Replacement Study (HERS) and Women's Health Initiative (WHI)) which have found no evidence for reduced stroke risk or severity. Rather, these recent trials have uncovered evidence for a higher risk of fatal stroke or worse outcome associated with the therapy (e.g. WEST & WHI trials).

This presentation will focus on what is currently known about the effects of oestrogen on the ischaemic brain, taken from studies on rodent models of focal and global cerebral ischaemia. Studies from our own laboratory and a number of laboratories in the USA reveal that the hormone possesses both beneficial and detrimental influences on the ischaemic brain. The outcome of oestrogen administration therefore depends on the balance between these opposing effects. The challenge is to identify the mechanisms responsible for both beneficial and detrimental effects and their time course in order to design oestrogen-related compounds or new treatment regimes which promote the beneficial effects but not the harmful effects of oestrogen.

Research on oestrogen and stroke in my laboratory has been generously supported by Research into Ageing.