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Nanomedicine is an emerging technology and the first nano-engineered medical products have come to light in the last decade. Transdermal drug delivery has significant advantages compared to other routes of drug administration. Nanoparticles unique physical and chemical properties enable transport of substances directly into the skin. The objective of this paper is to review different aspects of nanoparticle delivery, generally, and discuss its current use for transdermal hormone therapy. Transdermal estrogen therapy remains the most effective treatment for bothersome menopausal symptoms, particularly in those women for whom the potential adverse effects associated with "first pass" hepatic metabolism are to be avoided. Available alternatives for transdermal estrogen delivery include patches, gels, sprays and lotions. Other non-oral therapies which likewise avoid "first pass" hepatic metabolism include: subcutaneous implants and vaginal rings. Some of the transdermal products are associated with mild adverse skin effects such as redness and irritation, but more severe and bothersome consequences include blistering and tattooing. Even the mild adverse skin effects are frequently cited as reasons for discontinuation. Micellar nanoparticle estradiol emulsion (MNPEE) is a lotion-like therapy which constitutes an alternative transdermal delivery system not requiring the permeation enhancers or temporary skin digestion, both of which increase the possibility of irritation. MNPEE's advantages include low fluctuation of plasma estradiol concentrations, infrequent skin related adverse effects, and pleasant cosmetic-like moisturizing properties. The efficacy of MNPEE for management of menopausal vasomotor symptoms has been demonstrated in a randomized placebo controlled trial, and the product is FDA approved for management of moderate to severe vasomotor symptoms. None of the observed adverse effects in the MNPEE group were statistically different from the placebo group. Studies addressing inadvertent transference of estradiol to the male partners of menopausal women using this delivery technology have demonstrated small, but real amounts of transference, which do not exceed the normal physiological male estradiol range. MNPEE is safe and effective for treatment of vasomotor symptoms and represents the commercial validation of nanoparticle technology for transdermal delivery of estrogen therapy (ET) for postmenopausal women with vasomotor symptoms.