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What the FDA's updated guidance now reflects is a timing principle: for women who initiate hormone therapy within 10 years of menopause onset, or generally before age 60, the evidence profile looks materially different than it does for older populations

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In addition, it attenuates the nuclear translocation of NFATc1, a crucial downstream effector of the RANKL signaling pathway that is indispensable for the terminal stage of osteoclast differentiation (Mabilleau et al., 2016)

doi: 10.1016/j.neurobiolaging.2012.04.009

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