Abstract

Vaginal estrogen therapy at the lowest effective dose is generally recommended for the treatment of vulvar and vaginal atrophy (VVA), but not all women are candidates. Selective estrogen receptor modulators (SERMs) aim to elicit specific positive effects on targeted tissues with neutral or minimal negative effects on other tissues. This review compares the vaginal effects of currently available and investigational SERMs. Relevant English-language articles published between 1980 and 2012 were identified through the PubMed database (search string "[Selective Estrogen Receptor Modulator OR SERM] AND [Vulvar OR Vaginal] AND Atrophy"), article reference lists, and EMBASE searches for individual SERMs. Both authors reviewed all articles, which formed the basis of this narrative literature review. Activity profiles of SERMs in various tissues are distinct. Tamoxifen and arzoxifene have no specific positive vaginal effects but have reported variable or adverse gynecologic effects. Raloxifene does not improve VVA but can be used safely in combination with vaginal estrogen. Bazedoxifene has no demonstrated efficacy for VVA but, in combination with oral conjugated equine estrogens, improves the signs and symptoms of VVA. SERMs with positive vaginal effects (such as improvement in the vaginal maturation index, reduced vaginal pH, and improvement in the signs and symptoms of VVA) on postmenopausal symptomatic women include lasofoxifene (clinical development on hold) and ospemifene, which was recently approved for the treatment of VVA-related dyspareunia, with a class effect warning of potential venous thrombosis risk. SERMs that specifically target the pathophysiology underlying VVA may provide an alternative to vaginal or systemic estrogen therapy.

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