What is the Origin of WHI Timing Hypothesis?

This hypothesis was formulated after the WHI results, which showed increased cardiovascular risk in older women, contradicted previous observational data suggesting a cardioprotective effect. It originated from the clinical and scientific community seeking to explain this discrepancy, with non-human primate studies providing initial biological plausibility for an age-dependent effect.

What is the Mechanism of WHI Timing Hypothesis?

The theory proposes that when HT is initiated soon after menopause, in a relatively healthy vascular system, it may exert beneficial effects on the artery wall, preventing atherosclerosis. Conversely, initiating HT many years after menopause, in a vascular system with pre-existing, unstable atherosclerotic plaque, may provoke an inflammatory response, increasing the risk of plaque rupture, thrombosis, and subsequent cardiovascular events. Subgroup analyses of the WHI data offered some evidence to support this time-sensitive risk stratification.

WHI Timing Hypothesis

Meaning

The WHI Timing Hypothesis is a proposed framework that attempts to reconcile the conflicting cardiovascular outcomes observed in the Women’s Health Initiative (WHI) randomized trial with those from earlier observational studies of hormone therapy (HT). It posits that the effect of HT on cardiovascular disease is critically dependent on the age of the woman and the time elapsed since the onset of menopause. This theory suggests a “window of opportunity” for safe and potentially beneficial use.