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Ischaemic heart disease (IHD) is the leading cause of death worldwide in both women and men. Yet, the first manifestation of IHD is typically 5 to 10 years later in women than in men.1 The reasons for these sex differences in the age at onset of IHD are not fully understood. Female sex hormones, especially oestrogen, however, are often thought to explain the lower age-standardised incidence of IHD in women. In experimental studies, oestrogen has shown to have multiple cardioprotective properties, including reduced fibrosis and oxidative stress, stimulation of angiogenesis and vasodilation, and improved mitochondrial function. In contrast, randomised controlled trials on the use of hormone replacement therapy in postmenopausal women have shown little or no benefit for the prevention of IHD, although there may be some benefit among women who started treatment shortly after their menopause.2
A key challenge in robustly assessing the lifelong effects of oestrogen on health outcomes is the difficulty in accurately quantifying the lifelong level of exposure to oestrogen. Oestrogen levels in women rise and fall throughout life. Levels increase in puberty, marked by the menarche, fluctuate during the monthly menstrual cycle in the reproductive years and decline around the menopause. Reproductive events such as pregnancy and lactation also cause substantial changes in oestrogen levels, with high levels during pregnancy and low levels during lactation. In addition to these variations in endogenous oestrogen exposure (EOE), exposure to exogenous oestrogen, by use of the contraceptive pill or menopausal hormone therapy, complicates the quantification of lifelong exposure to oestrogen further. One possible approach to obtain a comprehensive measure of lifelong oestrogen levels would be to directly …
Contributors SAEP has written this editorial and takes full responsibility for its content.
Funding SAEP is supported by a VIDI Fellowship from the Dutch Organisation for Health Research and Development (ZonMw) (09150172010050).
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.