OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: SERMs that specifically target the pathophysiology underlying VVA 
may provide an alternative to vaginal or systemic estrogen therapy.