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To review the pharmacology, pharmacokinetics, safety, and efficacy of a gel containing estradiol that is applied to the skin.MEDLINE and EMBASE searches were conducted from 1966 to March 2005. Additional references were identified from bibliographies from selected studies in addition to approved product information.Estradiol gel is indicated for the relief of moderate to severe vasomotor symptoms in menopausal women, and moderate to severe symptoms of vulvar and vaginal atrophy. Women who are intolerant of the oral route, have had previous hypersensitivity skin reactions, or have had difficulties with adhesive patches are ideal candidates for estradiol gel.Estradiol gel can effectively reduce menopause symptoms with minimal side effects. Long-term safety data of estradiol gel are required.