An update on menopausal hormone replacement therapy in women and cardiovascular disease

This review presents the available evidence for effects of menopausal hormone replacement therapy (MHT), more specifically estrogen, and selective estrogen receptor modulators on the cardiovascular system with a focus on randomized controlled trials (RCTs) published since 2010.

In contrast to early observational studies, the Women's Health Initiative, the largest randomized controlled trial of MHT in generally healthy women, suggested harmful cardiovascular effects. Subsequent subanalyses of the Women's Health Initiative and other studies suggest the cardiovascular effects of MHT may vary by age and time since menopause, giving rise to a 'timing hypothesis'. Recent trials have looked at this issue by evaluating surrogate markers of cardiovascular disease (CVD) or CVD events adjudicated as secondary outcomes in RCTs and show a reduction in events with MHT.

Athough the data overall do not support the use of MHT or selective estrogen receptor modulator for primary prevention of CVD, evidence is accumulating that careful use of MHT for perimenopausal symptoms may not carry CVD harm. This review highlights some of the strengths and weaknesses of these recent reports. Ongoing studies of MHT will shed more light on the interaction between age or time after menopause and the vascular effects of MHT.