Evolution shaped menopause for ancestral environments where post-reproductive survival lasted only a few years — not three decades. The Grandmother Hypothesis and intergenerational reproductive conflict models both position menopause as an adaptive trait under high early-life mortality and short lifespans, where estrogen deficiency carried negligible selective cost. Modern medicine and nutrition have shattered that calculus, leaving women with a 30-year estrogen-deficient window their genome was never selected to navigate safely.
This evolutionary mismatch framing is genuinely useful and underutilized in clinical cardiology. Postmenopausal cardiovascular disease is the leading killer of women, yet treatment approaches rarely invoke the underlying endocrine-evolutionary architecture. By synthesizing comparative biology, epidemiology, and HRT clinical data, this analysis strengthens the case that the timing of ovarian aging — not just its occurrence — is mechanistically central to cardiovascular pathogenesis. The 'timing hypothesis' for HRT, which holds that estrogen therapy initiated near menopause onset confers cardiovascular protection while later initiation may not, gains evolutionary coherence here: ancestral PRLS was too brief for late-intervention biology to be selected for.
Critically, this is a review, not primary data — its strength lies in synthesis, not novel mechanistic discovery. The argument risks oversimplifying evolutionary causality. Still, reframing menopause as an endocrine transition with decades-long cardiovascular consequences — rather than a fertility endpoint — represents an important paradigm for aligning healthspan interventions with lifespan realities.
