The consequences of diminished plasma estrogens in post-menopausal women are reviewed. The various options for estrogen replacement therapy are discussed with reference to the risks and benefits of estrogen therapy. The changes in estrogen plasma concentrations and the resulting systemic actions that occur following vaginal administration of different formulations of estrogens are reviewed with reference to Estring, a new intra-vaginal formulation designed to give sustained delivery of estradiol to the vaginal mucosa. The possibility of Estring causing local, adverse, actions on the endometrium and the reasons why this is unlikely are described.