Abstract
Vulvar and vaginal atrophy (VVA) is a chronic, progressive medical condition prevalent among postmenopausal women, which produces symptoms such as dyspareunia, vaginal dryness, and vaginal irritation. Currently, the only prescription options are systemic and vaginal estrogen therapies that may be limited by concerns about long-term safety and breast cancer risk. Ospemifene is a tissue-selective estrogen agonist/antagonist (a selective estrogen receptor modulator) recently approved by the US Food and Drug Administration for treatment of dyspareunia, a symptom of VVA, due to menopause. Ospemifene, the first nonestrogen oral treatment for this indication, may provide an alternative to treatment with estrogen. Animal models with ospemifene suggest an inhibitory effect on growth of malignant breast tissue, but animal data cannot necessarily be extrapolated to humans. Clinical trials, including 3 long-term studies assessing the overall safety of ospemifene, support that ospemifene is generally well tolerated, with beneficial effects on the vagina, neutral effects on the breast, and minimal effects on the endometrium.
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Nath A, Sitruk-Ware R. Pharmacology and clinical applications of selective estrogen receptor modulators. Climacteric. 2009; 12(3):188–205.
Pickar JH, MacNeil T, Ohleth K. SERMs: progress and future perspectives. Maturitas. 2010;67(2):129–138.
Obiorah I, Jordan VC. Progress in endocrine approaches to the treatment and prevention of breast cancer. Maturitas. 2011; 70(4):315–321.
Tan O, Bradshaw K, Carr BR. Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: an up-to-date review. Menopause. 2012;19(1):109–117.
Santoro N, Komi J. Prevalence and impact of vaginal symptoms among postmenopausal women. J Sex Med. 2009;6(8):2133–2142.
Sturdee DW, Panay N; International Menopause Society Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric. 2010;13(6):509–522.
Goldstein I, Alexander JL. Practical aspects in the management of vaginal atrophy and sexual dysfunction in perimenopausal and postmenopausal women. J Sex Med. 2005;2(suppl 3):154–165.
Namba R, Young LJ, Maglione JE, et al. Selective estrogen receptor modulators inhibit growth and progression of premalignant lesions in a mouse model of ductal carcinoma in situ. Breast Cancer Res. 2005;7(6):R881–R889.
Taras TL, Wurz GT, DeGregorio MW. In vitro and in vivo biologic effects of ospemifene (FC-1271a) in breast cancer. J Steroid Biochem Mol Biol. 2001;77(4–5):271–279.
Wurz GT, Read KC, Marchisano-Karpman C, et al. Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice. J Steroid Biochem Mol Biol. 2005; 97(3):230–240.
McCall JL, DeGregorio MW. Pharmacologic evaluation of ospemifene. Expert Opin Drug Metab Toxicol. 2010;6(6):773–779.
Gennari L. Ospemifene hormos. Curr Opin Investig Drugs. 2004; 5(4):448–455.
Bachmann GA, Komi JO; Ospemifene Study Group. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause. 2010; 17(3):480–486.
Qu Q, Zheng H, Dahllund J, et al. Selective estrogenic effects of a novel triphenylethylene compound, FC1271a, on bone, cholesterol level, and reproductive tissues in intact and ovariectomized rats. Endocrinology. 2000;141(2):809–820.
Simon J, Lin V, Radovich C, Bachmann GA, The Ospemifene Study Group. One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. Menopause. 2013;20(4): 418–427.
Al-Baghdadi O, Ewies AA. Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an up-to-date overview. Climacteric. 2009;12(2):91–105.
Sprague BL, Trentham-Dietz A, Cronin KA. A sustained decline in postmenopausal hormone use: results from the National Health and Nutrition Examination Survey, 1999–2010. Obstet Gynecol. 2012;120(3):595–603.
Kingsberg S, Wysocki S, Magnus L, Krychman M. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Women’s VIews of Treatment Options for Menopausal Vaginal ChangEs) survey. J Sex Med. 2013;10(7):1790–1799.
Wurz GT, Soe LH, DeGregorio MW. Ospemifene, vulvovaginal atrophy, and breast cancer. Maturitas. 2013;74(3):220–225.
The North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American menopause society. Menopause. 2007;14(3 pt 1):355–369.
Matthews J, Wihlen B, Tujague M, Wan J, Strom A, Gustafsson JA. Estrogen receptor (ER) beta modulates ERalpha-mediated transcriptional activation by altering the recruitment of c-Fos and c-Jun to estrogen-responsive promoters. Mol Endocrinol. 2006; 20(3):534–543.
Zwart W, de Leeuw R., Rondaij M, Neefjes J, Mancini MA, Michalides R. The hinge region of the human estrogen receptor determines functional synergy between AF-1 and AF-2 in the quantitative response to estradiol and tamoxifen. J Cell Sci. 2010;123(pt 8):1253–1261.
Jordan VC, O’Malley BW. Selective estrogen-receptor modulators and antihormonal resistance in breast cancer. J Clin Oncol. 2007;25(36):5815–5824.
Wend K, Wend P, Krum SA. Tissue-specific effects of loss of estrogen during menopause and aging. Front Endocrinol (Lausanne). 2012;3:19.
Wardell SE, Kazmin D, McDonnell DP. Research resource: transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes. Mol Endocrinol. 2012;26(7):1235–1248.
Shao W, Brown M. Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy. Breast Cancer Res. 2004;6(1):39–52.
Speirs V, Skliris GP, Burdall SE, Carder PJ. Distinct expression patterns of ER alpha and ER beta in normal human mammary gland. J Clin Pathol. 2002;55(5):371–374.
Nilsson S, Koehler KF, Gustafsson JA. Development of subtype-selective oestrogen receptor-based therapeutics. Nat Rev Drug Discov. 2011;10(10):778–792.
Taylor HS. Designing the ideal selective estrogen receptor modulator–an achievable goal? Menopause. 2009;16(3):609–615.
Portman DJ, Bachmann G, Simon J, The Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013;20(6):623–630.
Bachmann G, Goldstein S, Lin V, Simon J, Portman D, Phelps M. Efficacy of ospemifene when used in the treatment of vulvar and vaginal atrophy for up to 52 weeks in postmenopausal women. Climacteric. 2011;14(suppl 1):92.
Simon J, Bachmann G, Goldstein S, Lin V, Portman D, Phelps M. Evaluation of the safety of daily ospemifene 60 mg for up to 1 year when used in the treatment of vulvar and vaginal atrophy in postmenopausal women (abstract). Climacteric. 2011;14(suppl 1):87.
Burich RA, Mehta NR, Wurz GT, et al. Ospemifene and 4-hydroxyospemifene effectively prevent and treat breast cancer in the MTag.Tg transgenic mouse model. Menopause. 2012; 19(1):96–103.
Morello KC, Wurz GT, DeGregorio MW. Pharmacokinetics of selective estrogen receptor modulators. Clin Pharmacokinet. 2003;42(4):361–372.
Levenson AS, Jordan VC. MCF-7: the first hormone-responsive breast cancer cell line. Cancer Res. 1997;57(15):3071–3078.
Simon J. Efficacy and safety of daily ospemifene 60 mg for up to 1 year when used in the treatment of vulvar and vaginal atrophy in postmenopausal women (abstract). Menopause. 2012;19(12): 1397–1398.
Osphena [package insert]. Florham Park, NJ: Shionogi Inc; 2013.
Ibe C, Simon JA. Vulvovaginal atrophy: current and future therapies (CME). J Sex Med. 2010;7(3):1042–1050.
Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351(9114):1451–1467.
Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999;281(23):2189–2197.
Evista [package insert]. Indianapolis, IN: Eli Lilly and Company; 2011.
Nolvadex [package insert]. Wilmington, DE: AstraZeneca; 2002.
Cummings SR, Ensrud K, Delmas PD, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med. 2010; 362(8):686–696.
Komm BS, Kharode YP, Bodine PV, Harris HA, Miller CP, Lyttle CR. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology. 2005; 146(9):3999–4008.
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Berga, S.L. Profile of Ospemifene in the Breast. Reprod. Sci. 20, 1130–1136 (2013). https://doi.org/10.1177/1933719113497290
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DOI: https://doi.org/10.1177/1933719113497290