Hormone replacement therapy and the association with coronary heart disease and overall mortality: Clinical application of the timing hypothesis

• HRT reduces CHD when initiated in recently postmenopausal women.
• HRT reduces total mortality when initiated in recently postmenopausal women.
• HRT cost effectively increases QALYs when initiated in recently postmenopausal women.
• Risks associated with HRT are rare.
• Long-term benefits of HRT outweigh risks.

Conclusions from randomized controlled trial (RCT) data over the past 10 years has spanned from presumed harm to consistency with observational data that hormone replacement therapy (HRT) decreases the risk for coronary heart disease (CHD) as well as overall mortality in women who are recently postmenopausal. Multiple clinical studies including randomized trials and observational studies converge with animal experimentation to show a consistency that HRT decreases CHD risk and overall mortality in primary prevention when HRT is started at the time of or soon after menopause. The totality of data supports the “timing” hypothesis that posits that HRT effects are dependent on when HRT is started in relation to age and/or time-since-menopause. The totality of data shows that HRT decreases CHD and overall morality when started in women who are less than 60 years old and/or less than 10 years postmenopausal, providing a “window-of-opportunity”. Further evidence shows that women who start HRT when in their 50s and continued for 5–30 years that there is an increase of 1.5 quality-adjusted life-years (QALYs). Additionally, HRT is highly cost-effective at $2438 per QALY gained. The totality of data converges to show a consistency between randomized trials and observational studies that when started in women at or near menopause and continued long-term, HRT decreases CHD and overall mortality compared with women who do not use HRT.This article is part of a Special Issue entitled ‘Menopause’.