The ramifications of endocrine and neural senescence converge in the hippocampus, particularly with respect to glutamatergic synapses. In this review, we will focus on current literature suggesting that potential synaptic alterations induced by estrogen in the hippocampus are mediated through interactions between ER-alpha and NMDA receptors. In addition, we will examine the data suggesting that these interactions may be uncoupled with aging. These studies demonstrate that while estrogen helps retain a youthful synaptic phenotype by some measures, the aged synapse may differ from the young synapse in several key respects that impact plasticity in general, and endocrine influences on the synapse, in particular.