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Clinical effects of selective estrogen receptor modulators on vulvar and vaginal atrophy

Pinkerton, JoAnn V. MD1; Stanczyk, Frank Z. PhD2

doi: 10.1097/GME.0b013e31829755ed
Review Article

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.

From the 1Department of Obstetrics and Gynecology, UVA Midlife Health Center, Charlottesville, VA; and 2Departments of Obstetrics and Gynecology, and Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA.

Received January 14, 2013; revised and accepted April 15, 2013.

J.V.P. and F.Z.S. had full control over the content, material, writing, and editing of this manuscript, and take full responsibility.

Funding/support: Writing assistance for this manuscript was funded by Shionogi Inc.

Financial disclosure/conflicts of interest: For the past 12 months, J.V.P. has served as consultant to Pfizer Inc, Noven Pharmaceuticals, Shionogi Inc, and DepoMed (fees to the University of Virginia); received grants and research support (fees to the University of Virginia) from Bionova and Endoceutics; and received travel funds from Pfizer Inc, Noven Pharmaceuticals, Shionogi Inc, and DepoMed. In the past 12 months, F.Z.S. has served as consultant to Merck and Co, Agile Therapeutics, and Shionogi Inc.

Address correspondence to: JoAnn V. Pinkerton, MD, Division of Midlife Health, Department of Obstetrics and Gynecology, UVA Midlife Health Center, PO Box 801104, Charlottesville, VA 22908-1104. E-mail:

© 2014 by The North American Menopause Society.