929
Views
33
CrossRef citations to date
0
Altmetric
Review

Pharmacotherapy for the treatment of vaginal atrophy

ORCID Icon, , &
Pages 821-835 | Received 18 Sep 2018, Accepted 22 Jan 2019, Published online: 21 Mar 2019

References

  • Farrell AE. Genitourinary syndrome of menopause. Aust Fam Physician. 2017;46(7): 481–484. PubMed PMID: 28697291; eng.
  • Karamanidis D, Tamiolakis D, Koutsougeras G, et al. Cigarette smoking and the degree of maturation of the vaginal squamous epithelium in postmenopausal women. Clin Exp Obstet Gynecol. 2001;28(4):274–276. PubMed PMID: 11838758; eng.
  • Gandhi J, Chen A, Dagur G, et al. Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016 Dec;215(6):704–711. PubMed PMID: 27472999; eng.
  • Panay N. Genitourinary syndrome of the menopause–dawn of a new era? Climacteric. 2015;18 (Suppl 1):13–17. PubMed PMID: 26366795; eng.
  • Portman DJ, Gass ML. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Maturitas. 2014 Nov;79(3):349–354. PubMed PMID: 25179577; eng.
  • Portman DJ, Gass ML. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Menopause (New York, NY). 2014 Oct;21(10):1063–1068. PubMed PMID: 25160739; eng.
  • Portman DJ, Gass ML. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. J Sex Med. 2014 Dec;11(12):2865–2872. PubMed PMID: 25155380; eng.
  • Portman DJ, Gass ML. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and The North American Menopause Society. Climacteric. 2014 Oct;17(5):557–563. PubMed PMID: 25153131; eng.
  • Forsberg JG. A morphologist’s approach to the vagina–age-related changes and estrogen sensitivity. Maturitas. 1995 Dec;22:S7–S15. PubMed PMID: 8775771; eng.
  • Buchanan DL, Kurita T, Taylor JA, et al. Role of stromal and epithelial estrogen receptors in vaginal epithelial proliferation, stratification, and cornification. Endocrinology. 1998 Oct;139(10):4345–4352. PubMed PMID: 9751518; eng.
  • Takashina R, Nakajima T, Umezu T, et al. Stratification of mouse vaginal epithelium 2. Identification of factors inducing stratification. Biol Reprod. 2018 May 11. PubMed PMID: 29762632; eng. DOI:10.1093/biolre/ioy113
  • Pessina MA, Hoyt RF Jr, Goldstein I, et al. Differential effects of estradiol, progesterone, and testosterone on vaginal structural integrity. Endocrinology. 2006 Jan;147(1):61–69. PubMed PMID: 16210369; eng.
  • Labrie F, Martel C, Pelletier G. Is vulvovaginal atrophy due to a lack of both estrogens and androgens? Menopause (New York, NY). 2017 Apr;24(4):452–461. PubMed PMID: 27875388; eng.
  • Berman JR, Almeida FG, Jolin J, et al. Correlation of androgen receptors, aromatase, and 5-alpha reductase in the human vagina with menopausal status. Fertil Steril. 2003 Apr;79(4):925–931. PubMed PMID: 12749432; eng.
  • Simon JA, Goldstein I, Kim NN, et al. The role of androgens in the treatment of genitourinary syndrome of menopause (GSM): International Society for the Study of Women’s Sexual Health (ISSWSH)expert consensus panel review. Menopause (New York, NY). 2018 Jul;25(7):837–847. PubMed PMID: 29870471; eng.
  • Labrie F, Derogatis L, Archer DF, et al. Effect of intravaginal prasterone on sexual dysfunction in postmenopausal women with vulvovaginal atrophy. J Sex Med. 2015 Dec;12(12):2401–2412. PubMed PMID: 26597311; eng.
  • Labrie F, Belanger A, Pelletier G, et al. Science of intracrinology in postmenopausal women. Menopause (New York, NY). 2017 Jun;24(6):702–712. PubMed PMID: 28098598; eng.
  • Merritt P, Stangl B, Hirshman E, et al. Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women. Brain Res. 2012 Nov 5;1483:54–62. PubMed PMID: 22985672; PubMed Central PMCID: PMCPMC3488281. eng.
  • Labrie F, Martel C, Balser J. Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in postmenopausal women: role of the ovary? Menopause (New York, NY). 2011 Jan;18(1):30–43. PubMed PMID: 20683211; eng.
  • Bikle D, Teichert A, Hawker N, et al. Sequential regulation of keratinocyte differentiation by 1,25(OH)2D3, VDR, and its coregulators. J Steroid Biochem Mol Biol. 2007 Mar;103(3–5):396–404. PubMed PMID: 17229570; eng.
  • Niki E, Traber MG. A history of vitamin E. Ann Nutr Metab. 2012;613:207–212. PubMed PMID: 23183290; eng.
  • Mirzapoiazova T, Lennon FE, Mambetsariev B, et al. Extracellular vesicles from caveolin-enriched microdomains regulate hyaluronan-mediated sustained vascular integrity. Int J Cell Biol. 2015;2015:481493. PubMed PMID: 26447809; PubMed Central PMCID: PMCPMC4581561. eng.
  • Kallak TK, Uvnas-Moberg K. Oxytocin stimulates cell proliferation in vaginal cell line Vk2E6E7. Post Reprod Health. 2017 Mar;23(1):6–12. PubMed PMID: 28381099; eng.
  • Al-Saqi SH, Jonasson AF, Naessen T, et al. Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women. Post Reprod Health. 2016 Mar;22(1):25–33. PubMed PMID: 26883689; eng.
  • de Landsheere L, Brieu M, Blacher S, et al. Elastin density: link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse? Int Urogynecol J. 2016 Apr;27(4):629–635. PubMed PMID: 26658755; eng. DOI:10.1007/s00192-015-2901-8
  • Jackson S, James M, Abrams P. The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence. BJOG. 2002 Mar;109(3):339–344. PubMed PMID: 11950190; eng.
  • Surazynski A, Jarzabek K, Haczynski J, et al. Differential effects of estradiol and raloxifene on collagen biosynthesis in cultured human skin fibroblasts. Int J Mol Med. 2003 Nov;12(5):803–809. PubMed PMID: 14533013; eng.
  • Boreham MK, Wai CY, Miller RT, et al. Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Clin Exp Obstet Gynecol. 2002;187(1):56–63.
  • Vetuschi A, D’Alfonso A, Sferra R, et al. Changes in muscularis propria of anterior vaginal wall in women with pelvic organ prolapse. Eur J Histochem. 2016 Feb 1;60(1):33-38. PubMed PMID: 26972719; PubMed Central PMCID: PMCPMC4800255. eng.
  • Berman JR, McCarthy MM, Kyprianou N. Effect of estrogen withdrawal on nitric oxide synthase expression and apoptosis in the rat vagina. Urology. 1998 Apr;51(4):650–656. PubMed PMID: 9586624; eng.
  • Min K, Munarriz R, Kim NN, et al. Effects of ovariectomy and estrogen and androgen treatment on sildenafil-mediated changes in female genital blood flow and vaginal lubrication in the animal model. Am J Clin Exp Obstet Gynecol. 2002;187(5):1370–1376.
  • Traish AM, Kim SW, Stankovic M, et al. Testosterone increases blood flow and expression of androgen and estrogen receptors in the rat vagina. J Sex Med. 2007;4(3):609–619.
  • Adham N, Schenk EA. Autonomic innervation of the rat vagina, cervix, and uterus and its cyclic cariation. Am J Obstet Gynecol. 1969 Jun 15;104(4):508–516. PubMed PMID: 5815047; eng.
  • Ting AY, Blacklock AD, Smith PG. Estrogen regulates vaginal sensory and autonomic nerve density in the rat. Biol Reprod. 2004 Oct;71(4):1397–1404. PubMed PMID: 15189832; eng.
  • Griebling TL, Liao Z, Smith PG. Systemic and topical hormone therapies reduce vaginal innervation density in post-menopausal women. Menopause (New York, NY). 2012 Jun;19(6):630–635. PubMed PMID: 22205148; PubMed Central PMCID: PMCPMC3319450. eng.
  • Basha M, Labelle EF, Northington GM, et al. Functional significance of muscarinic receptor expression within the proximal and distal rat vagina. Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1486–93. PubMed PMID: 19741053; PubMed Central PMCID: PMCPMC2777769. eng.
  • Jannini EA, Buisson O, Rubio-Casillas A. Beyond the G-spot: clitourethrovaginal complex anatomy in female orgasm. Nat Rev Urol. 2014 Sep;11(9):531–538. PubMed PMID: 25112854; eng.
  • Li T, Liao Q, Zhang H, et al. Anatomic distribution of nerves and microvascular density in the human anterior vaginal wall: prospective study. PloS one. 2014;9(11):e110239. PubMed PMID: 25379731; PubMed Central PMCID: PMCPMC4224374. eng.
  • Kingsberg SA, Wysocki S, Magnus L, et al. 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 Jul;10(7):1790–1799. PubMed PMID: 23679050; eng.
  • Palma F, Volpe A, Villa P, et al. Vaginal atrophy of women in postmenopause. Results from a multicentric observational study: the AGATA study. Maturitas. 2016 Jan;83:40–44. PubMed PMID: 26421474; eng.
  • SOGC clinical practice guidelines. The detection and management of vaginal atrophy. Number 145, May 2004. Int J Gynaecol Obstet. 2005 Feb;88(2):222–228. PubMed PMID: 15779109; eng.
  • Domoney C, Currie H, Panay N, et al. The CLOSER survey: impact of postmenopausal vaginal discomfort on women and male partners in the UK. Menopause Int. 2013 Jun;19(2):69–76. PubMed PMID: 23778561; eng.
  • Goldstein I, Dicks B, Kim NN, et al. Multidisciplinary overview of vaginal atrophy and associated genitourinary symptoms in postmenopausal women. Sex Med. 2013 Dec;1(2):44–53. PubMed PMID: 25356287; PubMed Central PMCID: PMCPMC4184497. eng.
  • Lev-Sagie A. Vulvar and vaginal atrophy: physiology, clinical presentation, and treatment considerations. Clin Obstet Gynecol. 2015 Sep;58(3):476–491. PubMed PMID: 26125962; eng.
  • Mouchamps E, Gaspard U. Inhibition of sexual desire associated with menopause. Revue medicale de Liege. 1999 May;54(5):489–494. PubMed PMID: 10394251; fre.
  • Nappi RE, Kingsberg S, Maamari R, et al. The CLOSER (CLarifying vaginal atrophy’s impact On SEx and Relationships) survey: implications of vaginal discomfort in postmenopausal women and in male partners. J Sex Med. 2013 Sep;10(9):2232–2241. PubMed PMID: 23809691; eng.
  • Nappi RE, Palacios S, Panay N, et al. Vulvar and vaginal atrophy in four European countries: evidence from the European REVIVE survey. Climacteric. 2016 Apr;19(2):188–197. PubMed PMID: 26581580; PubMed Central PMCID: PMCPMC4819825. eng.
  • Palacios S, Nappi RE, Bruyniks N, et al. The European Vulvovaginal Epidemiological Survey (EVES): prevalence, symptoms and impact of vulvovaginal atrophy of menopause. Climacteric J Int Menopause Soc. 2018 Jun;21(3):286–291. PubMed PMID: 29553288; eng.
  • Vieira-Baptista P, Marchitelli C, Haefner HK, et al. Deconstructing the genitourinary syndrome of menopause. Int Urogynecol J. 2017 May;28(5):675–679. PubMed PMID: 28293790; eng. DOI:10.1007/s00192-017-3295-6
  • Weber MA, Limpens J, Roovers JP. Assessment of vaginal atrophy: a review. Int Urogynecol J. 2015 Jan;26(1):15–28. PubMed PMID: 25047897; eng.
  • Kingsberg SA, Krychman M, Graham S, et al. The women’s empower survey: identifying women’s perceptions on vulvar and vaginal atrophy and its treatment. J Sex Med. 2017 Mar;14(3):413–424. PubMed PMID: 28202320; eng.
  • Krychman M, Graham S, Bernick B, et al. The women’s empower survey: women’s knowledge and awareness of treatment options for vulvar and vaginal atrophy remains inadequate. J Sex Med. 2017 Mar;14(3):425–433. PubMed PMID: 28202319; eng.
  • Nappi RE, Palacios S, Bruyniks N, et al. The burden of vulvovaginal atrophy on women’s daily living: implications on quality of life from a face-to-face real-life survey. Menopause (New York, NY). 2018 Nov 12. PubMed PMID: 30422932; eng. DOI:10.1097/gme.0000000000001260
  • Bachmann G. Urogenital ageing: an old problem newly recognized. Maturitas. 1995 Dec;22:S1–S5. PubMed PMID: 8775770; eng.
  • Huang AJ, Gregorich SE, Kuppermann M, et al. Day-to-day impact of vaginal aging questionnaire: a multidimensional measure of the impact of vaginal symptoms on functioning and well-being in postmenopausal women. Menopause (New York, NY). 2015 Feb;22(2):144–154. PubMed PMID: 24983271; PubMed Central PMCID: PMCPMC4280352. eng.
  • Kao A, Binik YM, Kapuscinski A, et al. Dyspareunia in postmenopausal women: a critical review. Pain Res Manag. 2008 May–Jun;13(3):243–254. PubMed PMID: 18592062; PubMed Central PMCID: PMCPMC2671314. eng.
  • Mitro SD, Harlow SD, Randolph JF, et al. Chronic vulvar pain in a cohort of post-menopausal women: atrophy or vulvodynia? Women’s Midlife Health. 2016;2. PubMed PMID: 28127441; PubMed Central PMCID: PMCPMC5260822. eng. DOI:10.1186/s40695-016-0017-z
  • Donders GGG, Bellen G, Grinceviciene S, et al. Aerobic vaginitis: no longer a stranger. Res Microbiol. 2017 Nov–Dec;168(9–10):845–858. PubMed PMID: 28502874; eng.
  • Lewis FM. Vulval symptoms after the menopause - not all atrophy! Post Reprod Health. 2015 Dec;21(4):146–150. PubMed PMID: 26424289; eng.
  • Greendale GA, Zibecchi L, Petersen L, et al. Development and validation of a physical examination scale to assess vaginal atrophy and inflammation. Climacteric. 1999 Sep;2(3):197–204. PubMed PMID: 11910597; eng.
  • van der Laak JA, Schijf CP, Kerstens HM, et al. Development and validation of a computerized cytomorphometric method to assess the maturation of vaginal epithelial cells. Cytometry. 1999 Mar 1;35(3):196–202. PubMed PMID: 10082300; eng.
  • Tucker KM, Godha K, Mirkin S, et al. Vaginal pH: a simple assessment highly correlated with vaginal morphology and symptoms in postmenopausal women. Menopause (New York, NY). 2018 Jul;25(7):762–766. PubMed PMID: 29509598; eng.
  • Tuntiviriyapun P, Panyakhamlerd K, Triratanachat S, et al. Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy? Climacteric J Int Menopause Soc. 2015 Apr;18(2):246–251. PubMed PMID: 25374401; eng.
  • Donders GG. Microscopy of the bacterial flora on fresh vaginal smears. Infect Dis Obstet Gynecol. 1999;74:177–179. PubMed PMID: 10449264; PubMed Central PMCID: PMCPMC1784739. Eng.
  • Donders GG. Definition and classification of abnormal vaginal flora. Best Pract Res Clin Obstetrics Gynaecol. 2007 Jun;21(3):355–373. PubMed PMID: 17434799; Eng.
  • Donders GG, Marconi C, Bellen G, et al. Effect of short training on vaginal fluid microscopy (wet mount) learning. J Low Genit Tract Dis. 2015 Apr;19(2):165–169. PubMed PMID: 25148226; eng.
  • Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the women’s health initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701–1712. PubMed PMID: 15082697; eng.
  • Glaser RL, Zava DT, Wurtzbacher D. Pilot study: absorption and efficacy of multiple hormones delivered in a single cream applied to the mucous membranes of the labia and vagina. Gynecol Obstet Invest. 2008;662:111–118. PubMed PMID: 18446040; eng.
  • Del Pup L, Di Francia R, Cavaliere C, et al. Promestriene, a specific topic estrogen. Review of 40 years of vaginal atrophy treatment: is it safe even in cancer patients? Anticancer Drugs. 2013 Nov;24(10):989–998. PubMed PMID: 24080714; eng.
  • Oyarzun MFG, Castelo-Branco C. Local hormone therapy for genitourinary syndrome of menopause in breast cancer patients: is it safe? Gynecol Endocrinol. 2017 Jun;33(6):418–420. PubMed PMID: 28277141; eng.
  • Sun AJ, Lin SQ, Jing LH, et al. Safety of promestriene capsule used in postmenopausal atrophic vaginitis. Zhonghua fu chan ke za zhi. 2009 Aug;44(8):593–596. PubMed PMID: 20003787; chi.
  • Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2016 Aug; 31(8):Cd001500. PubMed PMID: 27577677; eng.
  • Illston JD, Wheeler TL, Parker CR, et al. Low-dose 17-β-estradiol cream for vaginal atrophy in a cohort without prolapse: serum levels and vaginal response including tissue biomarkers associated with tissue remodeling. Maturitas. 2015 Aug;81(4):475–479. PubMed PMID: 26115591; PubMed Central PMCID: PMCPMC4515379. eng.
  • Archer DF, Constantine GD, Simon JA, et al. TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol. Menopause (New York, NY). 2017 May;24(5):510–516. PubMed PMID: 28002201; PubMed Central PMCID: PMCPMC5404400. eng.
  • Constantine GD, Bouchard C, Pickar JH, et al. Consistency of effect with a low-dose, estradiol vaginal capsule (TX-004HR): evaluating improvement in vaginal physiology and moderate-to-severe dyspareunia in subgroups of postmenopausal women. J Women’s Health. 2017 Jun 1;26(6):616–623. PubMed PMID: 28355090; PubMed Central PMCID: PMCPMC5512333. eng.
  • Heimer GM, Englund DE. Plasma oestriol following vaginal administration: morning versus evening insertion and influence of food. Maturitas. 1986 Oct;8(3):239–243. PubMed PMID: 3784920; eng.
  • Bergink EW. Oestriol receptor interactions: their biological importance and therapeutic implications. Acta Endocrinologica Supplementum. 1980;233: 9–16. PubMed PMID: 6996407; eng.
  • Birkhauser M. Prevention of osteoporosis by estrogens. Revue medicale de la Suisse romande. 1995 Feb;115(2):113–120. PubMed PMID: 7886365; fre.
  • van der Vies J. The pharmacology of oestriol. Maturitas. 1982 Dec;4(4):291–299. PubMed PMID: 7169963; eng.
  • Griesser H, Skonietzki S, Fischer T, et al. Low dose estriol pessaries for the treatment of vaginal atrophy: a double-blind placebo-controlled trial investigating the efficacy of pessaries containing 0.2mg and 0.03mg estriol. Maturitas. 2012 Apr;71(4):360–368. PubMed PMID: 22285095; eng.
  • Head KA. Estriol: safety and efficacy. Alternative Med Rev J Clin Ther. 1998 Apr;3(2):101–113. PubMed PMID: 9577246; eng.
  • Unlu C, Donders G. Use of lactobacilli and estriol combination in the treatment of disturbed vaginal ecosystem: a review. J Turk Ger Gynecol Assoc. 2011;124:239–246. PubMed PMID: 24592002; PubMed Central PMCID: PMCPMC3939257. eng.
  • Donders GG, Van Bulck B, Van de Walle P, et al. Effect of lyophilized lactobacilli and 0.03 mg estriol (Gynoflor(R)) on vaginitis and vaginosis with disrupted vaginal microflora: a multicenter, randomized, single-blind, active-controlled pilot study. Gynecol Obstet Invest. 2010;70(4):264–272. PubMed PMID: 21051846.
  • Ozkinay E, Terek MC, Yayci M, et al. The effectiveness of live lactobacilli in combination with low dose oestriol (Gynoflor) to restore the vaginal flora after treatment of vaginal infections. BJOG. 2005 Feb;112(2):234–240. PubMed PMID: 15663590; eng.
  • Jaisamrarn U, Triratanachat S, Chaikittisilpa S, et al. Ultra-low-dose estriol and lactobacilli in the local treatment of postmenopausal vaginal atrophy. Climacteric J Int Menopause Soc. 2013 Jun;16(3):347–355. PubMed PMID: 23347400; PubMed Central PMCID: PMCPMC3786549. eng.
  • Kanne B, Jenny J. Local administration of low-dose estriol and vital lactobacillus acidophilus in postmenopause. Gynakologische Rundschau. 1991;31(1): 7–13. PubMed PMID: 1906830; ger.
  • Capobianco G, Wenger JM, Meloni GB, et al. Triple therapy with lactobacilli acidophili, estriol plus pelvic floor rehabilitation for symptoms of urogenital aging in postmenopausal women. Arch Gynecol Obstet. 2014 Mar;289(3):601–608. PubMed PMID: 24057079; eng.
  • Donders G, Bellen G, Neven P, et al. Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor(R)) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors. Eur J Clin Microbiol Infect Dis. 2015 Oct;34(10):2023–2028. PubMed PMID: 26223323; PubMed Central PMCID: PMCPMC4565868. eng.
  • Buchholz S, Mogele M, Lintermans A, et al. Vaginal estriol-lactobacilli combination and quality of life in endocrine-treated breast cancer. Climacteric J Int Menopause Soc. 2015 Apr;18(2):252–259. PubMed PMID: 25427450; Eng.
  • Diller M, Schuler S, Buchholz S, et al. Effects of estriol on growth, gene expression and estrogen response element activation in human breast cancer cell lines. Maturitas. 2014 Apr;77(4):336–343. PubMed PMID: 24529907.
  • Donders G, Neven P, Moegele M, et al. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor((R))) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat. 2014 Jun;145(2):371–379. PubMed PMID: 24718774; PubMed Central PMCID: PMCPMC4025172.
  • Bhamra RK, Margolis MB, Liu JH, et al. A randomized, multiple-dose parallel study to compare the pharmacokinetic parameters of synthetic conjugated estrogens, A, administered as oral tablet or vaginal cream. Menopause (New York, NY). 2011 Apr;18(4):393–399. PubMed PMID: 21107298; eng.
  • Farrell R. ACOG committee opinion no. 659 summary: the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer. Obstet Gynecol. 2016 Mar;127(3):618–619. PubMed PMID: 26901332; eng.
  • Alvisi S, Baldassarre M, Martelli V, et al. Effects of ospemifene on vaginal epithelium of post-menopausal women. Gynecol Endocrinol. 2017 Dec;33(12):946–950. PubMed PMID: 28562130; eng.
  • Bachmann GA, Komi JO. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause (New York, NY). 2010 May–Jun;17(3):480–486. PubMed PMID: 20032798; eng.
  • Archer DF, Altomare C, Jiang W, et al. Ospemifene’s effects on lipids and coagulation factors: a post hoc analysis of phase 2 and 3 clinical trial data. Menopause (New York, NY). 2017 Oct;24(10):1167–1174. PubMed PMID: 28509812; PubMed Central PMCID: PMCPMC5617371. eng.
  • 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 (New York, NY). 2012 Jan;19(1):96–103. PubMed PMID: 21926925; PubMed Central PMCID: PMCPMC3246110. eng.
  • 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 Jun;77(4–5):271–279. PubMed PMID: 11457665; eng.
  • 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 Nov;97(3):230–240. PubMed PMID: 16153821; eng.
  • Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015 Nov;100(11):3975–4011. PubMed PMID: 26444994; eng.
  • Schiavi MC, Di Pinto A, Sciuga V, et al. Prevention of recurrent lower urinary tract infections in postmenopausal women with genitourinary syndrome: outcome after 6 months of treatment with ospemifene. Gynecol Endocrinol. 2018 Feb;34(2):140–143. PubMed PMID: 28853624; eng.
  • Kangas L, Harkonen P, Vaananen K, et al. Effects of the selective estrogen receptor modulator ospemifene on bone in rats. Hormone Metab Res. 2014 Jan;46(1):27–35. PubMed PMID: 24108389; eng.
  • Komi J, Lankinen KS, DeGregorio M, et al. Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women. J Bone Miner Metab. 2006;24(4):314–318. PubMed PMID: 16816926; eng.
  • Fernandes T, Pedro AO, Baccaro LF, et al. Hormonal, metabolic, and endometrial safety of testosterone vaginal cream versus estrogens for the treatment of vulvovaginal atrophy in postmenopausal women: a randomized, placebo-controlled study. Menopause (New York, NY). 2018 Jun;25(6):641–647. PubMed PMID: 29462095; eng.
  • Bell RJ, Rizvi F, Islam RM, et al. A systematic review of intravaginal testosterone for the treatment of vulvovaginal atrophy. Menopause (New York, NY). 2018 Jun;25(6):704–709. PubMed PMID: 29286987; eng.
  • Labrie F, Archer DF, Koltun W, et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause (New York, NY). 2016 Mar;23(3):243–256. PubMed PMID: 26731686; eng.
  • Archer DF, Labrie F, Montesino M, et al. Comparison of intravaginal 6.5mg (0.50%) prasterone, 0.3mg conjugated estrogens and 10mug estradiol on symptoms of vulvovaginal atrophy. J Steroid Biochem Mol Biol. 2017 Nov;174:1–8. PubMed PMID: 28323042; eng.
  • Bouchard C, Labrie F, Archer DF, et al. Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy. Climacteric J Int Menopause Soc. 2015;18(4):590–607. PubMed PMID: 25511551; eng.
  • Visser M, Coelingh Bennink HJ. Clinical applications for estetrol. J Steroid Biochem Mol Biol. 2009 Mar;114(1–2):85–89. PubMed PMID: 19167495; eng.
  • Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric J Int Menopause Soc. 2008;11 Suppl 1:47–58. PubMed PMID: 18464023; eng.
  • Coelingh Bennink HJT, Verhoeven C, Zimmerman Y, et al. Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women. Climacteric J Int Menopause Soc. 2017 Jun;20(3):285–289. PubMed PMID: 28267365; eng.
  • Chen WY, Abatangelo G. Functions of hyaluronan in wound repair. Wound Repair Regen. 1999 Mar–Apr;7(2):79–89. PubMed PMID: 10231509; eng.
  • Jokar A, Davari T, Asadi N, et al. Comparison of the hyaluronic acid vaginal cream and conjugated estrogen used in treatment of vaginal atrophy of menopause women: a randomized controlled clinical trial. Int J Community Based Nurs Midwifery. 2016 Jan;4(1):69–78. PubMed PMID: 26793732; PubMed Central PMCID: PMCPMC4709811. eng.
  • Stute P. Is vaginal hyaluronic acid as effective as vaginal estriol for vaginal dryness relief? Arch Gynecol Obstet. 2013 Dec;288(6):1199–1201. PubMed PMID: 24178484; eng.
  • Serati M, Bogani G, Di Dedda MC, et al. A comparison between vaginal estrogen and vaginal hyaluronic for the treatment of dyspareunia in women using hormonal contraceptive. Eur J Obstet Gynecol Reprod Biol. 2015 Aug;191:48–50. PubMed PMID: 26070127; eng.
  • Munblit D, Abrol P, Sheth S, et al. Levels of growth factors and IgA in the colostrum of women from Burundi and Italy. Nutrients. 2018 Sep 3;10(9). PubMed PMID: 30177587; PubMed Central PMCID: PMCPMC6164593. eng.
  • Vailati S, Melloni E, Riscassi E, et al. Evaluation of the effects of a new intravaginal gel, containing purified bovine colostrum, on vaginal blood flow and vaginal atrophy in ovariectomized rat. Sex Med. 2013 Dec;1(2):35–43. PubMed PMID: 25356286; PubMed Central PMCID: PMCPMC4184496. eng.
  • Nappi RE, Cagnacci A, Becorpi AM, et al. Monurelle Biogel((R)) vaginal gel in the treatment of vaginal dryness in postmenopausal women. Climacteric J Int Menopause Soc. 2017 Oct;20(5):467–475. PubMed PMID: 28657769; eng.
  • Grant MD, Marbella A, Wang AT, et al. AHRQ comparative effectiveness reviews. Menopausal symptoms: comparative effectiveness of therapies. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015.
  • Le Donne M, Caruso C, Mancuso A, et al. The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause. Arch Gynecol Obstet. 2011 Jun;283(6):1319–1323. PubMed PMID: 20577750; eng.
  • Lima SM, Bernardo BF, Yamada SS, et al. Effects of Glycine max (L.) Merr. soy isoflavone vaginal gel on epithelium morphology and estrogen receptor expression in postmenopausal women: a 12-week, randomized, double-blind, placebo-controlled trial. Maturitas. 2014 Jul;78(3):205–211. PubMed PMID: 24856055; eng.
  • Leiblum S, Bachmann G, Kemmann E, et al. Vaginal atrophy in the postmenopausal woman. The importance of sexual activity and hormones. JAMA. 1983 Apr 22–29;249(16):2195–2198. PubMed PMID: 6834616; eng.
  • Waetjen LE, Crawford SL, Chang PY, et al. Factors associated with developing vaginal dryness symptoms in women transitioning through menopause: a longitudinal study. Menopause (New York, NY). 2018 Oct;25(10):1094–1104. PubMed PMID: 29916947; PubMed Central PMCID: PMCPMC6136974. eng.
  • Pinkerton JV, Bushmakin AG, Komm BS, et al. Relationship between changes in vulvar-vaginal atrophy and changes in sexual functioning. Maturitas. 2017 Jun;100:57–63. PubMed PMID: 28539177; eng.
  • Lee A, Mr L, Lee HH, et al. Vitamin D proliferates vaginal epithelium through RhoA expression in postmenopausal atrophic vagina tissue. Mol Cells. 2017 Sep 30;40(9):677–684. PubMed PMID: 28843271; PubMed Central PMCID: PMCPMC5638775. eng.
  • Rad P, Tadayon M, Abbaspour M, et al. The effect of vitamin D on vaginal atrophy in postmenopausal women. Iran J Nurs Midwifery Res. 2015 Mar–Apr;20(2):211–215. PubMed PMID: 25878698; PubMed Central PMCID: PMCPMC4387645. eng.
  • Golmakani N, Parnan Emamverdikhan A, Zarifian A, et al. Vitamin E as alternative local treatment in genitourinary syndrome of menopause: a randomized controlled trial. Int Urogynecol J. 2018 Jul 3. PubMed PMID: 29971469; eng. DOI:10.1007/s00192-018-3698-z
  • Parnan Emamverdikhan A, Golmakani N, Sas T, et al. A survey of the therapeutic effects of Vitamin E suppositories on vaginal atrophy in postmenopausal women. Iran J Nurs Midwifery Res. 2016 Sep–Oct;21(5):475–481. PubMed PMID: 27904630; PubMed Central PMCID: PMCPMC5114791. eng.
  • 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(11):e26602. PubMed PMID: 22073175; PubMed Central PMCID: PMCPMC3206802. eng.
  • Gambacciani M, Levancini M. Short-term effect of vaginal erbium laser on the genitourinary syndrome of menopause. Minerva Ginecol. 2015 Apr;67(2):97–102. PubMed PMID: 25763800; eng.
  • Gaspar A, Brandi H, Gomez V, et al. Efficacy of erbium: yaglaser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause. Lasers Surg Med. 2017 Feb;49(2):160–168. PubMed PMID: 27546524; PubMed Central PMCID: PMCPMC5347840. eng.
  • Perino A, Cucinella G, Gugliotta G, et al. Is vaginal fractional CO2 laser treatment effective in improving overactive bladder symptoms in post-menopausal patients? Preliminary results. Eur Rev Med Pharmacol Sci. 2016 Jun;20(12):2491–2497. PubMed PMID: 27383297; eng.
  • Pagano I. Evaluation of the CO(2) laser therapy on vulvo-vaginal atrophy (VVA) in oncological patients: preliminary results. J Cancer Ther. 2017 May;8(5):452–463. PubMed PMID: 29104812; PubMed Central PMCID: PMCPMC5669269. eng.
  • Salvatore S, Nappi RE, Zerbinati N, et al. A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric J Int Menopause Soc. 2014 Aug;17(4):363–369. PubMed PMID: 24605832; eng.
  • Walter JE, Larochelle A. No. 358-intravaginal laser for genitourinary syndrome of menopause and stress urinary incontinence. J Obstetrics Gynaecol Can. 2018 Apr;40(4):503–511. PubMed PMID: 29680080; eng.
  • Pitsouni E, Grigoriadis T, Falagas ME, et al. Laser therapy for the genitourinary syndrome of menopause. A systematic review and meta-analysis. Maturitas. 2017;103:78–88.
  • Vicariotto F, Raichi M. Technological evolution in the radiofrequency treatment of vaginal laxity and menopausal vulvo-vaginal atrophy and other genitourinary symptoms: first experiences with a novel dynamic quadripolar device. Minerva Ginecol. 2016 Jun;68(3):225–236. PubMed PMID: 27206062; eng.
  • Vicariotto F, Des F, Faoro V, et al. Dynamic quadripolar radiofrequency treatment of vaginal laxity/menopausal vulvo-vaginal atrophy: 12-month efficacy and safety. Minerva Ginecol. 2017 Aug;69(4):342–349. PubMed PMID: 28608667; eng.
  • Arunkalaivanan A, Kaur H, Onuma O. Laser therapy as a treatment modality for genitourinary syndrome of menopause: a critical appraisal of evidence. Int Urogynecol J. 2017 May;28(5):681–685. PubMed PMID: 28154914; eng. DOI:10.1007/s00192-017-3282-y

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.