Hodis · The Journal of steroid biochemistry and molecular biology 2014 · narrative review · n=?

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

Cited 66 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing existing randomized trials, observational studies, and animal data.

PubMed 23851166 · doi:10.1016/j.jsbmb.2013.06.011 · record verified 2026-08-29

What was done

This narrative review synthesized findings from randomized controlled trials, observational cohorts, and animal experiments evaluating the "timing hypothesis" of hormone replacement therapy (HRT) for the primary prevention of coronary heart disease (CHD) and all-cause mortality according to age and time since menopause.

What was found

The authors reported that HRT reduces CHD risk and overall mortality when initiated in women younger than 60 years old or fewer than 10 years postmenopausal. For women starting HRT in their 50s and continuing for 5 to 30 years, cited data indicate a gain of 1.5 quality-adjusted life-years (QALYs) at a cost-effectiveness ratio of $2,438 per QALY gained.

Why it matters

This paper outlines the clinical rationale for a "window of opportunity" around menopause onset, reconciling apparent discrepancies between early observational studies and later randomized trials regarding HRT and cardiovascular outcomes.

Limits

The abstract describes a narrative synthesis rather than a formal systematic review or meta-analysis with predefined search criteria and quality appraisal. Specific effect sizes, confidence intervals, adverse event profiles (such as thromboembolism or breast cancer risk), and distinctions between estrogen-only versus combined regimens are not reported in the abstract.

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