Management of symptomatic vulvovaginal atrophy: 2013 position statement of the North American Menopause Society

Menopause

Volumn 20, Issue 9, 2013, Pages 888-902

[No Author Info available]

Author keywords

Dyspareunia; Menopause; Ospemifene; Vaginal dryness; Vaginal estrogen; Vulvovaginal atrophy

Indexed keywords

4 HYDROXYBENZOIC ACID ESTER; ANASTROZOLE; AROMATASE INHIBITOR; BAZEDOXIFENE; CONJUGATED ESTROGEN; ESTRADIOL; ESTRADIOL ACETATE; ESTRAGYN; ESTRONE; EXEMESTANE; FOLLITROPIN; FULVESTRANT; GESTAGEN; GONADORELIN AGONIST; GONADORELIN ANTAGONIST; LASOFOXIFENE; LETROZOLE; LUBRICATING AGENT; NON PRESCRIPTION DRUG; OSPEMIFENE; PETROLATUM; PLACEBO; PLANT MEDICINAL PRODUCT; PRASTERONE; PROPYLENE GLYCOL; SILICONE; TAMOXIFEN; TESTOSTERONE; UNCLASSIFIED DRUG; AGENTS USED INTRAVAGINALLY; ESTROGEN;

ANATOMY; ARTICLE; BREAST CANCER; CANCER CHEMOTHERAPY; CLINICAL EFFECTIVENESS; DIFFERENTIAL DIAGNOSIS; DISEASE SEVERITY; DISTRESS SYNDROME; DRUG SAFETY; DYSPAREUNIA; ENDOMETRIUM; ESTRADIOL BLOOD LEVEL; ESTROGEN THERAPY; FOLLITROPIN BLOOD LEVEL; HEALTH EDUCATION; HORMONAL THERAPY; HUMAN; HYSTERECTOMY; LOW DRUG DOSE; MASTALGIA; MEDICAL HISTORY; MEDICAL SOCIETY; NAUSEA; OVARIECTOMY; PATIENT PREFERENCE; PHYSICAL EXAMINATION; PHYSIOLOGY; POSTMENOPAUSE; PRESCRIPTION; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); SEXUAL BEHAVIOR; SEXUAL DYSFUNCTION; SEXUAL HEALTH; TREATMENT DURATION; VAGINA ATROPHY; VAGINA BLEEDING; VAGINA DISCHARGE; VAGINA RING; VAGINAL DRYNESS; VENOUS THROMBOEMBOLISM; ATROPHY; FEMALE; INTRAVAGINAL DRUG ADMINISTRATION; METABOLISM; MIDDLE AGED; NORTH AMERICA; PATHOLOGY; PRACTICE GUIDELINE; PROCEDURES; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; STANDARDS; VAGINA; WOMEN'S HEALTH;

ADMINISTRATION, INTRAVAGINAL; ATROPHY; DYSPAREUNIA; ESTROGEN REPLACEMENT THERAPY; ESTROGENS; FEMALE; HUMANS; MIDDLE AGED; NORTH AMERICA; POSTMENOPAUSE; PRACTICE GUIDELINES AS TOPIC; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; SOCIETIES, MEDICAL; VAGINA; VAGINAL CREAMS, FOAMS, AND JELLIES; WOMEN'S HEALTH;

EID: 84883608600     PISSN: 10723714     EISSN: 15300374     Source Type: Journal    
DOI: 10.1097/GME.0b013e3182a122c2     Document Type: Article

References (149)

1. Lindau ST, Schumm LP. Laumann EO, Levinson W, O-Muircheartaigh CA, Waite LJ. A study of sexuality and health among older adults in the United States. N Engl J Med 2007;357:762-774.
2. Santoro N, Komi J. Prevalence and impact of vaginal symptoms among postmenopausal women. J Sex Med 2009;6:2133-2142.
3. Nappi RE, Kokot-Kierepa M. Vaginal Health: Insights, Views & Attitudes (VIVA)Vresults from an international survey. Climacteric 2012; 15:36-44.
4. Simon JA, Kokot-Kierepa M, Goldstein J, Nappi RE. Vaginal health in the United States: results from the Vaginal Health: Insights, Views & Attitudes survey [published online ahead of print April 15, 2013]. Menopause doi: 10.1097/GME.0b013e318287342d.
5. Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (Real Women-s Views of Treatment Options forMenopausal Vaginal Changes) survey [published online ahead of print May 16, 2013]. J Sex Med doi: 10.1111/jsm. 12190.
6. Pastore LM, Carter RA, Hulka BS, Wells E. Self-reported urogenital symptoms in postmenopausal women: Women-s Health Initiative. Maturitas 2004;49:292-303.
7. 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; quiz 370-371.
8. Chen GD, Oliver RH, Leung BS, Lin LY, Yeh J. Estrogen receptor alpha and beta expression in the vaginal walls and uterosacral ligaments of premenopausal and postmenopausal women. Fertil Steril 1999;71: 1099-1102.
9. Gebhart JB, Rickard DJ, Barrett TJ, et al. Expression of estrogen receptor isoforms alpha and beta messenger RNA in vaginal tissue of premenopausal and postmenopausal women. Am J Obstet Gynecol 2001;185:1325-1330.
10. Hodgins MB, Spike RC, Mackie RM, MacLean AB. An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina. Br J Obstet Gynaecol 1998;105:216-222.
11. Griebling TL, Liao Z, Smith PG. Systemic and topical hormone therapies reduce vaginal innervation density in postmenopausal women. Menopause 2012;19:630-635.
12. Bachmann GA, Cheng RJ, Rovner E. Vulvovaginal complaints. In: Lobo RA, ed. Treatment of the Postmenopausal Woman: Basic and Clinical Aspects, 3rd ed. Burlington, MA: Academic Press, 2007:263-270.
13. Gorodeski GI. Estrogen modulation of epithelial permeability in cervicalvaginal cells of premenopausal and postmenopausal women. Menopause 2007;14:1012-1019.
14. Donders GG, Bosmans E, Dekeersmaecker A, Vereecken A, Van Bulck B, Spitz B. Pathogenesis of abnormal vaginal bacterial flora. Am J Obstet Gynecol 2000;182:872-878.
15. Roy S, Caillouette JC, Roy T, Faden JS. Vaginal pH is similar to folliclestimulating hormone for menopause diagnosis. Am J Obstet Gynecol 2004;190:1272-1277.
16. Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA 2011;108(suppl 1):4680-4687.
17. Lamont RF, Sobel JD, Akins RA. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011;118:533-549.
18. Lai SK, Hida K, Shukair S, et al. Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virol 2009;83:11196-11200.
19. Wiesenfeld HC, Hillier SL, KrohnMA, Landers DV, Sweet RL. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 2003;36:663-668.
20. Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis 2003;37:319-325.
21. Pybus V, Onderdonk AB. Microbial interactions in the vaginal ecosystem, with emphasis on the pathogenesis of bacterial vaginosis. Microbes Infect 1999;1:285-292.
22. Martin HL, Richardson BA, Nyange PM, et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 1999;180:1863-1868.
23. Gupta K, Stapleton AE, Hooton TM, Roberts PL, Fennell CL, Stamm WE. Inverse association of H2O2-producing lactobacilli and vaginal Escherichia coli colonization in women with recurrent urinary tract infections. J Infect Dis 1998;178:446-450.
24. Hummelen R, Macklaim JM, Bisanz JE, et al. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One 2011;6:e26602.
25. Baker GC, Smith JJ, Cowan DA. Review and re-analysis of domainspecific 16S primers. J Microbiol Methods 2003;55:541-555.
26. Schmidt TM. The maturing of microbial ecology. Int Microbiol 2006; 9:217-223.
27. Weng L, Rubin EM, Bristow J. Application of sequence-based methods in human microbial ecology. Genome Res 2006;16:316-322.
28. Burton JP, Devillard E, Cadieux PA, Hammond JA, Reid G. Detection of Atopobium vaginae in postmenopausal women by cultivationindependent methods warrants further investigation. J Clin Microbiol 2004;42:1829-1831.
29. Martin DH. The microbiota of the vagina and its influence on women-s health and disease. Am J Med Sci 2012;343:2-9.
30. Brotman RM, Ravel J, Cone RA, Zenilman JM. Rapid fluctuation of the vaginal microbiota measured by Gram stain analysis. Sex Transm Infect 2010;86:297-302.
31. Levine KB, Williams RE, Hartmann KE. Vulvovaginal atrophy is strongly associated with female sexual dysfunction among sexually active postmenopausal women. Menopause 2008;15(4 pt 1):661-666.
32. Barnabei VM, Cochrane BB, Aragaki AK, et al. Women-s Health Initiative Investigators. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women-s Health Initiative. Obstet Gynecol 2005;105(5 pt 1):1063-1073.
33. Kingsberg SA. The sexual health benefits of oral low-dose estrogen plus progestogen and vaginal estrogen for postmenopausal women. Menopause 2009;16:224-225.
34. Wylie KR. Sexuality and the menopause. J Br Menopause Soc 2006; 12:149-152.
35. American College of Obstetricians and Gynecologists Women-s Health Care Physicians. Sexual dysfunction. Obstet Gynecol 2004;104(suppl 4): 85S-91S.
36. Dennerstein L, Lehert P, Burger H, Dudley E. Factors affecting sexual functioning of women in the mid-life years. Climacteric 1999;2:254-262.
37. Tan O, Bradshaw K, Carr BR. Management of vulvovaginal atrophyrelated sexual dysfunction in postmenopausal women: an up-to-date review. Menopause 2012;19:109-117.
38. Knobf MT. The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors. Oncologist 2006;11:96-110.
39. Ganz PA, Desmond KA, Belin TR, Meyerowitz BE, Rowland JH. Predictors of sexual health in women after a breast cancer diagnosis. J Clin Oncol 1999;17:2371-2380.
40. Kirchheiner K, Fidarova E, Nout RA, et al. Radiation-induced morphological changes in the vagina. Strahlenther Onkol 2012;188:1010-1017.
41. Conde DM, Pinto-Neto AM, Cabello C, Sá DS, Costa-Paiva L, Martinez EZ. Menopause symptoms and quality of life in women aged 45 to 65 years with and without breast cancer. Menopause 2005;12:436-443.
42. Greendale GA, Petersen L, Zibecchi L, Ganz PA. Factors related to sexual function in postmenopausal women with a history of breast cancer. Menopause 2001;8:111-119.
43. Burwell SR, Case LD, Kaelin C, Avis N. Sexual problems in younger women after breast cancer surgery. J Clin Oncol 2006;24:2815-2821.
44. Arora NK, Gustafson DH, Hawkins RP, et al. Impact of surgery and chemotherapy on the quality of life of younger women with breast carcinoma: a prospective study. Cancer 2001;92:1288-1298.
45. Ganz PA, Greendale GA, Petersen L, Zibecchi L, Kahn B, Belin TR. Managing menopausal symptoms in breast cancer survivors: results of a randomized controlled trial. J Natl Cancer Inst 2000;92:1054-1064.
46. Ganz PA, Coscarelli A, Fred C, Kahn B, Polinsky ML, Petersen L. Breast cancer survivors: psychosocial concerns and quality of life. Breast Cancer Res Treat 1996;38:183-199.
47. Baumgart J, Nilsson K, Evers AS, Kallak TK, Poromaa IS. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause 2013;20:162-168.
48. Cella D, Fallowfield L, Barker P, Cuzick J, Locker G, Howell A; ATAC Trialsta9 Group. Quality of life of postmenopausal women in the ATAC (BArimidex,[ tamoxifen alone or in combination) trial after completion of 5 years-adjuvant treatment for early stage breast cancer. Breast Cancer Res Treat 2006;100:273-284.
49. Whelan TJ, Pritchard KI. Managing patients on endocrine therapy: focus on quality-of-life issues. Clin Cancer Res 2006;12(3 pt 2): 1056s-1060s.
50. Whelan TJ, Goss PE, Ingle JN, et al. Assessment of quality of life in MA.17: a randomized placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol 2005;23: 6931-6940.
51. Fallowfield L, Cella D, Cuzick J, Francis S, Locker G, Howell A. Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. J Clin Oncol 2004;22:4261-4271.
52. Wyeth Pharmaceuticals. REVEAL: Revealing Vaginal Effect At mid-Life. Surveys of Postmenopausal Women and Health Care Professionals Who Treat Postmenopausal Women. May 2009. www.revealsurvey.com/pdf/reveal-survey-results. pdf. Accessed June 14, 2013.
53. Fisher BK. Normal anatomy of the vulva. In: Fisher BK, Margesson LJ, eds. Genital Skin Disorders: Diagnosis and Treatment. St Louis, MO: Mosby, 1998:99-107.
54. Sobel JD, Reichman O, Misra D, Yoo W. Prognosis and treatment of desquamative inflammatory vaginitis. Obstet Gynecol 2011;117:850-855.
55. Capobianco G. Donolo E, Borghero G, Dessole F, Cherchi PL, Dessole S. Effects of intravaginal estriol and pelvic floor rehabilitation on urogenital aging in postmenopausal women. Arch Gynecol Obstet 2012;285: 397-403.
56. Lee YK, Chung HH, Kim JW, Park NH, Song YS, Kang SB. Vaginal pH-balanced gel for the control of atrophic vaginitis among breast cancer survivors: a randomized controlled trial. Obstet Gynecol 2011;117: 922-927.
57. Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas 1996;23:259-263.
58. Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril 1994;61:178-180.
59. Dezzutti CS, Brown ER, Moncla B, et al. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity. PLos One 2012;7:e48328.
60. Brown JM, Hess KL, Brown S, Murphy C, Waldman AL, Hezareh M. Intravaginal practices and risk of bacterial vaginosis and candidiasis infection among a cohort of women in the United States. Obstet Gynecol 2013;121:773-780.
61. Reed SD, Newton KM, LaCroix AZ, Grothaus LC, Grieco VS, Erlich K. Vaginal, endometrial, and reproductive hormone findings: randomized placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: The Herbal Alternatives for Menopause (HALT) Study. Menopause 2008;15:51-58.
62. North American Menopause Society. The 2012 hormone therapy position paper of The North American Menopause Society. Menopause 2012;19:257-271.
63. Smith RN, Studd JW. Recent advances in hormone replacement therapy. Br J Hosp Med 1993;49:799-808.
64. Long CY, Liu CM, Hsu SC, Wu CH, Wang CL, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women. Menopause 2006;13:737-743.
65. Cardozo L, Bachmann G, McClish D, Fonda D, Birgerson L. Metaanalysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol 1998;92(4 pt 2):722-727.
66. Ayton RA, Darling GM,Murkies AL, et al. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. Br J Obstet Gynaecol 1996;103:351-358.
67. Nachtigall L. Clinical trial of the estradiol vaginal ring in the U.S. Maturitas 1995;22(suppl):S43-S47.
68. Manonai J, Theppisai U, Suthutvoravut S, Udomsubpayakul U, Chittacharoen A. The effect of estradiol vaginal tablet and conjugated estrogen cream on urogenital symptoms in postmenopausal women: a comparative study. J Obstet Gynaecol Res 2001;27:255-260.
69. Rioux JE, Devlin C, Gelfand MM, Steinberg WM, Hepburn DS. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause 2000;7:156-161.
70. Barentsen R, van de Weijer PH, Schram JH. Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. Eur J Obstet Gynecol Reprod Biol 1997;7:73-80.
71. Casper F, Petri E. Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: a comparative and a placebo-controlled multicenter study. Vaginal Ring Study Group. Int Urogynecol J Pelvic Floor Dysfunct 1999;10:171-176.
72. Henriksson L, Stjernquist M, Boquist L, Alander U, Selinus I. A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy. Am J Obstet Gynecol 1994;171:624-632.
73. Lose G, Englev E. Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms. BJOG 2000;107:1029-1034.
74. Weisberg E, Ayton R, Darling G, et al. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric 2005;8:83-92.
75. Eriksen PS, Rasmussen H. Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol 1992;44:137-144.
76. Dugal R, Hesla K, SLrdal T, Aase KH, Lilleeidet O, WickstrLm E. Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy. Acta Obstet Gynecol Scand 2000;79: 293-297.
77. Foidart JM, Vervliet J, Buytaert P. Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. Maturitas 1991;13:99-107.
78. Garcia LE. Efficiency of vaginal ovules of estriol for treatment of symptoms of menopause. Investigacion Medica Internacional 1993;19: 159-165.
79. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2006;CD001500.
80. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993;329:753-757.
81. Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infection in postmenopausal women. Am J Obstet Gynecol 1999;180:1072-1079.
82. Nelken RS, Ozel BZ, Leegant AR, Felix JC, Mishell DR Jr. Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause 2011;18:962-966.
83. Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev 2012;10:CD001405.
84. Townsend MK, Curhan GC, Resnick NM, Grodstein F. The incidence of urinary incontinence across Asian, black, and white women in the United States. Am J Obstet Gynecol 2010;202:378.e1-e7.
85. Hendrix SL, Cochrane BB, Nygaard IE, et al. Effects of estrogen with and without progestin on urinary incontinence. JAMA 2005;293:935-948.
86. Waetjen LE, Brown JS, Vittinghoff E, et al. The effect of ultralow-dose transdermal estradiol on urinary incontinence in postmenopausal women. Obstet Gynecol 2005;106(5 pt 1):946-952.
87. Grady D, Brown JS, Vittinghoff E, Applegate W, Varner E, Snyder T; HERS Research Group. Postmenopausal hormones and incontinence: the Heart and Estrogen/Progestin Replacement Study. Obstet Gynecol 2001;97:116-120.
88. Maalouf NM, Sato AH, Welch BJ, et al. Postmenopausal hormone use and the risk of nephrolithiasis: results from the Women's Health Initiative hormone therapy trials. Arch Intern Med 2010;170:1678-1685.
89. Lee JS, Ettinger B, Stanczyk FZ, et al. Comparison of methods to measure low serum estradiol levels in postmenopausal women. J Clin Endocrinol Metab 2006;91:3791-3797.
90. Schmidt G, Andersson SB, Nordle O, Johansson CJ, Gunnarsson PO. Release of 17-beta-oestradiol from a vaginal ring in postmenopausal women: pharmacokinetic evaluation. Gynecol Obstet Invest 1994;38: 253-260.
91. Naessen T, Rodriguez-Macias K. Endometrial thickness and uterine diameter not affected by ultralow doses of 17beta-estradiol in elderly women. Am J Obstet Gynecol 2002;186:944-947.
92. Santen RJ, Pinkerton JV, Conaway M, et al. Treatment of urogenital atrophy with low-dose estradiol: preliminary results. Menopause 2002;9: 179-187.
93. Notelovitz M, Funk S, Nanavati N, Mazzeo M. Estradiol absorption from vaginal tablets in postmenopausal women. Obstet Gynecol 2002; 99:556-562.
94. Eugster-Hausmann M, Waitzinger J, Lehnick D. Minimized estradiol absorption with ultra-low-dose 10 microg 17beta-estradiol vaginal tablets. Climacteric 2010;13:219-227.
95. Rigg LA, Hermann H, Yen SS. Absorption of estrogens from vaginal creams. N Engl J Med 1978;298:195-197.
96. Handa VL, Bachus KE, Johnston WW, Robboy SJ, Hammond CB. Vaginal administration of low-dose conjugated estrogens: systemic absorption and effects on the endometrium. Obstet Gynecol 1994; 84:215-218.
97. Stanczyk FZ, Lee JS, Santen RJ. Standardization of steroid hormone assays: why, how, and when? Cancer Epidemiol Biomarkers Prev 2007; 16:1713-1719.
98. Fischer G, Bradford J. Vulvovaginal candidiasis in postmenopausal women: the role of hormone replacement therapy. J Low Genit Tract Dis 2011;15:263-267.
99. Dennerstein GJ, Ellis DH. Oestrogen, glycogen and vaginal candidiasis. Aust N Z J Obstet Gynaecol 2001;41:326-328.
100. Ulrich LS, Naessen T, Elia D, Goldstein JA, Eugster-Hausmann M. Endometrial safety of ultra-low-dose Vagifem 10 microg in postmenopausal women with vaginal atrophy. Climacteric 2010;13:228-237.
101. Simon J, Nachtigall L, Gut R, Lang E, Archer DF, Utian W. Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. Obstet Gynecol 2008;112:1053-1060.
102. Obiorah I, Jordan VC. 2012 NAMS/PfizerVWulf H. Utian Endowed Lecture. Scientific rational for postmenopause delay in the use of conjugated equine estrogens among postmenopausal women that causes reduction in breast cancer incidence and mortality. Menopause 2013;20:372-382.
103. Mastaglia SR, Bagur A, Royer M, Yankelevich D, Sayegh F, Oliveri B. Effect of endogenous estradiol levels on bone resorption and bone mineral density in healthy postmenopausal women: a prospective study. Climacteric 2009;12:49-58.
104. Bagur A, Oliveri B, Mautalen C, et al. Low levels of endogenous estradiol protect bone mineral density in young postmenopausal women. Climacteric 2004;7:181-188.
105. Cicinelli E, Di Naro E, De Ziegler D, et al. Placement of the vaginal 17beta-estradiol tablets in the inner or outer one third of the vagina affects the preferential delivery of 17beta-estradiol toward the uterus or periurethral areas, thereby modifying efficacy and endometrial safety. Am J Obstet Gynecol 2003;189:55-58.
106. Tourgeman DE, Boostanfar R, Chang L, Lu J, Stanczyk FZ, Paulson RJ. Is there evidence for preferential delivery of ovarian estradiol to the endometrium? Fertil Steril 2001;75:1156-1158.
107. Fanchin R, De Ziegler D, Bergeron C, Righini C, Torrisi C, Frydman R. Transvaginal administration of progesterone. Obstet Gynecol 1997;90: 396-401.
108. Ross D, Cooper AJ, Pryse-Davies J, Bergeron C, Whitehead MI. Randomized, double-blind, dose-ranging study of endometrial effects of a vaginal progesterone gel in estrogen-treated postmenopausal women. Am J Obstet Gynecol 1997;177:937-941.
109. De Ziegler D, Bulletti C, De Monstier B, Jääskeläinen AS. The first uterine pass effect. Ann N Y Acad Sci 1997;828:291-299.
110. Winneker RC, Harris HA. Progress and prospects in treating postmenopausal vaginal atrophy. Clin Pharmacol Ther 2011;89:129-132.
111. Biglia N, Peano E, Sgandurra P, et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010;26:404-412.
112. Kendall A, Dowsett M, Folkerd E, Smith I. Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 2006;17:584-587.
113. Col NF, Kim JA, Chleboskwi RT. Menopausal hormone therapy after breast cancer: a meta-analysis and critical appraisal of the evidence. Breast Cancer Res 2005;7:R535-R540.
114. Le Ray I, Dell'Aniello S, Bonnetain F, Azoulay L, Suissa S. Local estrogen therapy and risk of breast cancer recurrence among hormonetreated patients: a nested case-control study. Breast Cancer Res Treat 2012;135:603-609.
115. Wills S, Ravipati A, Venuturumilli P, et al. Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator. J Oncol Pract 2012;8:144-148.
116. Estrace cream [package insert]. Rockaway, NJ: Warner Chilcott, LLC, 2011.
117. Premarin vaginal cream [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals, 2012.
118. Estragyn vaginal cream [product monograph]. Concord, Ontario, Canada: Triton Pharma Inc, 2010.
119. Estring [package insert]. New York: Pharmacia & Upjohn Co, 2008.
120. Femring [package insert]. Rockaway, NJ: Warner Chilcott Inc, 2005.
121. Vagifem [package insert]. Princeton, NJ: Novo Nordisk Inc, 2012.
122. Bachmann G, Bouchard C, Hoppe D, et al. Efficacy and safety of lowdose regimens of conjugated estrogens cream administered vaginally. Menopause 2009;16:719-727.
123. American Association of Sexuality Educators, Counselors and Therapists (AASECT) www.aasect.org.
124. Simon J, Nachtigall L, Ulrich LG, Eugster-Hausmann M, Gut R. Endometrial safety of ultra-low-dose estradiol vaginal tablets. Obstet Gynecol 2010;116:876-883.
125. Johnston SL, Farrell SA, Bouchard C, et al; SOGC Joint Committee-Clinical Practice Gynaecology and Urogynaecology. The detection and management of vaginal atrophy. J Obstet Gynaecol Can 2004;26:503-515.
126. American College of Obstetricians and Gynecologists Women-s Health Care Physicians. Genitourinary tract changes. Obstet Gynecol 2004; 104(suppl 4):56S-61S.
127. Portman DJ, Bachmann GA, Simon JA; Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 2013;20:623-630.
128. Bachmann GA, Komi JO; Ospemifene Study Group. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause 2010;17:480-486.
129. Simon JA, Lin VH, 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;20:418-427.
130. Osphena [package insert]. Florham Park, NJ: Shionogi Inc, 2013.
131. Wurz GT, Soe LH, Degregorio MW. Ospemifene, vulvovaginal atrophy, and breast cancer [published online ahead of print January 15, 2013]. Maturitas doi 10.1016/j. maturitas.2012.12.002.
132. Vogel VG, Costantino JP, Wickerham DL, et al.; National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295:2727-2741. Erratum in: JAMA. 2007;298(9):973; JAMA. 2006;296(24):2926.
133. Land SR, Wickerham DL, Costantino JP, et al. Patient-reported symptoms and quality of life during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295:2742-2751. Erratum in: JAMA. 298(9):973.
134. Davies GC, HusterWJ, Lu Y, Plouffe L, Lakshmanan M. Adverse events reported by postmenopausal women in controlled trials with raloxifene. Obstet Gynecol 1999;93:558-565.
135. Parsons A, Merritt D, Rosen A, Heath H 3rd, Siddhanti S, Plouffe L Jr; Study Group on the Effects of Raloxifene HCI With Low-Dose Premarin Vaginal Cream. Effect of raloxifene on the response to conjugated estrogen vaginal cream or nonhormonal moisturizers in postmenopausal vaginal atrophy. Obstet Gynecol 2003;101:346-352.
136. Pinkerton JV, Shifren JL, La Valleur J, Rosen A, Roesinger M, Siddhanti S. Influence of raloxifene on the efficacy of an estradiolreleasing ring for treating vaginal atrophy in postmenopausal women. Menopause 2003;10:45-52.
137. Stovall DW, Utian QWH, Gass ML, et al. The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety. Menopause 2007;14(3 pt 1):510-517.
138. Fisher B, Costantino JP,Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90:1371-1388.
139. Chollet JA. Update on alternative therapies for vulvovaginal atrophy. Patient Prefer Adherence 2011:5:533-536.
140. Portman D, Moffett A, Kerber I, Drosman S, Somayaji V, Lee A. Vaginal effects of lasofoxifene and raloxifene: preliminary evidence suggests lasofoxifene, but not raloxifene, improves indices of vaginal health [abstract]. Menopause 2004;11:675. Abstract P-87.
141. LaCroix AZ, Powles T, Osborne CK, et al.; PEARL Investigators. Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women. J Natl Cancer Inst 2010;102:1706-1715.
142. Bachmann G, Gass M, Kagan R, Moffett A, Barcomb L, Symons J. Lasofoxifene (LASO), a next generation selective estrogen response modulator (SERM) improves dyspareunia in postmenopausal women with vaginal atrophy (VA) [abstract]. Menopause 2005;12:238.
143. Lobo RA, Pinkerton JV, Gass ML, et al. Evaluation of bazedoxifene/ conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril 2009;92:1025-1038.
144. Kagan R, Williams RS, Pan K, Mirkin S, Pickar JH. A randomized, placebo-and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women. Menopause 2010;17:281-289.
145. Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause 2009;16:907-922.
146. Labrie F, Archer D, Bouchard C, et al. High internal consistency and efficacy of intravaginal DHEA for vaginal atrophy. Gynecol Endocrinol 2010;26:524-532.
147. Chi CC, Kirtschig G, Baldo M, Brackenbury F, Lewis F, Wojnarowska F. Topical interventions for genital lichen sclerosus. Cochrane Database Syst Rev. 2011;7:CD008240.
148. Witherby S, Johnson J, Demers L, et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. Oncologist 2011;16:424-431.
149. Nappi RE, Davis SR. The use of hormone therapy for the maintenance of urogynecological and sexual health post WHI. Climacteric 2012;15:267-274.