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The "timing hypothesis" or "critical window" hypothesis, now supported by substantial mechanistic and clinical data, proposes that estrogen's cardiovascular protective effects are contingent on initiating therapy while vascular endothelium remains estrogen-responsive, generally within ten years of menopause onset or before age 60 [8]

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As hypothesized, the 18 O content in cyanidin ( 8 ) increased as a function of equilibration time and the expected level (47.4%) for stochastic incorporation of a single 18 O label was reached after 15 min of pretreatment (Fig