{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:34:46Z","timestamp":1785818086155,"version":"3.56.0"},"reference-count":154,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpharmsci.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2023,6]]},"DOI":"10.1016\/j.xphs.2023.02.021","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T02:03:59Z","timestamp":1677636239000},"page":"1566-1585","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"title":["Intravaginal Drug Delivery Systems to Treat the Genitourinary Syndrome of Menopause: Towards the Design of Safe and Efficacious Estrogen-loaded Prototypes"],"prefix":"10.1016","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0507-0422","authenticated-orcid":false,"given":"Ahmed","family":"Abdelgader","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-5405","authenticated-orcid":false,"given":"Mershen","family":"Govender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8640-4350","authenticated-orcid":false,"given":"Pradeep","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-1529","authenticated-orcid":false,"given":"Yahya E.","family":"Choonara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"11","key":"10.1016\/j.xphs.2023.02.021_bib0001","first-page":"884","article-title":"Hormone therapy and other treatments for symptoms of menopause","volume":"94","author":"Hill","year":"2016","journal-title":"Am Fam Physician"},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0002","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1111\/j.1743-6109.2009.01335.x","article-title":"Prevalence and impact of vaginal symptoms among postmenopausal women","volume":"6","author":"Santoro","year":"2009","journal-title":"J Sex Med"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0003","article-title":"The genitourinary syndrome of menopause: an overview of the recent data","volume":"12","author":"Angelou","year":"2020","journal-title":"Cureus"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0004","first-page":"15","article-title":"Clinical efficacy of hormonal and nonhormonal agents in the treatment of vulvovaginal atrophy","volume":"27","author":"Ilhan","year":"2021","journal-title":"JMM"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0005","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/jmwh.13277","article-title":"Genitourinary syndrome of menopause","volume":"66","author":"Marino","year":"2021","journal-title":"J Midwifery Womens Health"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0006","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1089\/jwh.2017.6515","article-title":"A randomized, multicenter, double-blind, study to evaluate the safety and efficacy of estradiol vaginal cream 0.003% in postmenopausal women with vaginal dryness as the most bothersome symptom","volume":"27","author":"Archer","year":"2018","journal-title":"J Women's Health"},{"key":"10.1016\/j.xphs.2023.02.021_bib0007","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.maturitas.2021.04.005","article-title":"Topical estrogens and non-hormonal preparations for postmenopausal vulvovaginal atrophy: an EMAS clinical guide","volume":"148","author":"Hirschberg","year":"2021","journal-title":"Maturitas"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0008","doi-asserted-by":"crossref","first-page":"59","DOI":"10.7257\/1053-816X.2016.36.2.59","article-title":"Genitourinary syndrome of menopause and vaginal estrogen use","volume":"36","author":"Steele","year":"2016","journal-title":"Urologic Nurs"},{"issue":"11","key":"10.1016\/j.xphs.2023.02.021_bib0009","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1097\/GME.0000000000000465","article-title":"One-year treatment persistence with local estrogen therapy in postmenopausal women diagnosed as having vaginal atrophy","volume":"22","author":"Portman","year":"2015","journal-title":"Menopause"},{"issue":"10","key":"10.1016\/j.xphs.2023.02.021_bib0010","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s40266-019-00700-w","article-title":"Practical treatment considerations in the management of genitourinary syndrome of menopause","volume":"36","author":"Kagan","year":"2019","journal-title":"Drugs aging"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0011","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.ajog.2016.07.045","article-title":"Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management","volume":"215","author":"Gandhi","year":"2016","journal-title":"Am J Obstet Gynecol"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0012","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.maturitas.2015.07.020","article-title":"Update on management of genitourinary syndrome of menopause: a practical guide","volume":"82","author":"Palacios","year":"2015","journal-title":"Maturitas"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0013","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0168-3659(99)00148-0","article-title":"Design of an intravaginal ring for the controlled delivery of 17\u03b2-estradiol as its 3-acetate ester","volume":"61","author":"Woolfson","year":"1999","journal-title":"J Controlled Release"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0014","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1208\/s12249-008-9073-5","article-title":"A review of current intravaginal drug delivery approaches employed for the prophylaxis of HIV\/AIDS and prevention of sexually transmitted infections","volume":"9","author":"Ndesendo","year":"2008","journal-title":"AAPS PharmSciTech"},{"issue":"12","key":"10.1016\/j.xphs.2023.02.021_bib0015","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.3390\/pharmaceutics12121185","article-title":"A bilayer vaginal tablet for the localized delivery of disulfiram and 5-fluorouracil to the cervix","volume":"12","author":"Abidin","year":"2020","journal-title":"Pharmaceutics"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0016","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11884-013-0224-5","article-title":"Role of topical vaginal estrogen in the treatment of overactive bladder","volume":"9","author":"Fine","year":"2014","journal-title":"Curr Bladder Dysfunct Rep"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0017","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3390\/gels8020099","article-title":"Application of sol\u2013gels for treatment of gynaecological conditions\u2014physiological perspectives and emerging concepts in intravaginal drug delivery","volume":"8","author":"Thapa","year":"2022","journal-title":"Gels"},{"issue":"12","key":"10.1016\/j.xphs.2023.02.021_bib0018","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1097\/GME.0000000000000996","article-title":"Vaginal estrogen in the treatment of genitourinary syndrome of menopause and risk of endometrial cancer: an assessment of recent studies provides reassurance","volume":"24","author":"Pinkerton","year":"2017","journal-title":"Menopause"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0019","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/13697130802585576","article-title":"Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an up-to-date overview","volume":"12","author":"Al-Baghdadi","year":"2009","journal-title":"Climacteric"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0020","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00192-012-2009-3","article-title":"The vagina as a route for drug delivery: a review","volume":"24","author":"Srikrishna","year":"2013","journal-title":"Int Urogynecol J"},{"key":"10.1016\/j.xphs.2023.02.021_bib0021","doi-asserted-by":"crossref","first-page":"571","DOI":"10.2147\/PPA.S22940","article-title":"Efficacy and safety of ultra-low-dose Vagifem (10 mcg)","volume":"5","author":"Chollet","year":"2011","journal-title":"Patient Pref Adher"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0022","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/13697137.2014.947254","article-title":"Vaginal administration of estradiol: effects of dose, preparation and timing on plasma estradiol levels","volume":"18","author":"Santen","year":"2015","journal-title":"Climacteric"},{"issue":"10","key":"10.1016\/j.xphs.2023.02.021_bib0023","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S1461-5347(00)00296-0","article-title":"The scope and potential of vaginal drug delivery","volume":"3","author":"Vermani","year":"2000","journal-title":"Pharm Sci Technol Today"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0024","doi-asserted-by":"crossref","first-page":"494","DOI":"10.3390\/pharmaceutics6030494","article-title":"Bioadhesive mini-tablets for vaginal drug delivery","volume":"6","author":"Hiorth","year":"2014","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.xphs.2023.02.021_bib0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.carbpol.2021.117832","article-title":"Synthesis, characterization, and evaluation of BDDE crosslinked chitosan-TGA hydrogel encapsulated with genistein for vaginal atrophy","volume":"260","author":"Yang","year":"2021","journal-title":"Carbohydr Polym"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0026","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jconrel.2004.11.034","article-title":"The vagina as a route for systemic drug delivery","volume":"103","author":"Hussain","year":"2005","journal-title":"J Controlled Release"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0027","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1080\/03639045.2017.1386203","article-title":"Mucoadhesive tablets for the vaginal delivery of progesterone: in vitro evaluation and pharmacokinetics\/pharmacodynamics in female rabbits","volume":"44","author":"Hassan","year":"2018","journal-title":"Drug Dev Ind Pharm"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0028","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3390\/md18050249","article-title":"Carrageenan-based acyclovir mucoadhesive vaginal tablets for prevention of genital herpes","volume":"18","author":"Pacheco-Quito","year":"2020","journal-title":"Mar Drugs"},{"key":"10.1016\/j.xphs.2023.02.021_bib0029","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ejps.2008.12.009","article-title":"Polymer\u2013lipid based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate","volume":"36","author":"Albertini","year":"2009","journal-title":"Eur J Pharm Sci"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0030","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1208\/pt030320","article-title":"Mucoadhesive vaginal tablets as veterinary delivery system for the controlled release of an antimicrobial drug, acriflavine","volume":"3","author":"Gavini","year":"2002","journal-title":"AAPS PharmSciTech"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12249-019-1439-3","article-title":"Mucoadhesive in situ gelling liquid crystalline precursor system to improve the vaginal administration of drugs","volume":"20","author":"De Ara\u00fajo","year":"2019","journal-title":"AAPS PharmSciTech"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0032","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/GME.0000000000000592","article-title":"A randomized, double-blind, placebo-controlled phase 2 pilot trial evaluating a novel, vaginal softgel capsule containing solubilized estradiol","volume":"23","author":"Pickar","year":"2016","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0033","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.maturitas.2020.06.005","article-title":"Comparison of the effects of pueraria mirifica gel and of placebo gel on the vaginal microenvironment of postmenopausal women with genitourinary syndrome of menopause (GSM)","volume":"140","author":"Sritonchai","year":"2020","journal-title":"Maturitas"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0034","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00192-014-2464-0","article-title":"Assessment of vaginal atrophy: a review","volume":"26","author":"Weber","year":"2015","journal-title":"Int Urogynecol J"},{"key":"10.1016\/j.xphs.2023.02.021_bib0035","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.maturitas.2020.06.018","article-title":"Viewing symptoms associated with Vulvovaginal Atrophy (VVA)\/Genitourinary syndrome of menopause (GSM) through the estro-androgenic lens\u2013Cluster analysis of a web-based Italian survey among women over 40","volume":"140","author":"Nappi","year":"2020","journal-title":"Maturitas"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0036","doi-asserted-by":"crossref","first-page":"S245","DOI":"10.1016\/S0002-9378(98)70555-1","article-title":"Urogenital aging\u2014a hidden problem","volume":"178","author":"Samsioe","year":"1998","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0037","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/j.1751-486X.2012.01776.x","article-title":"An overview of chronic vaginal atrophy and options for symptom management","volume":"16","author":"Woods","year":"2012","journal-title":"Nurs Womens Health"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0038","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.bpobgyn.2007.08.010","article-title":"Intravaginal oestrogen and progestin administration: advantages and disadvantages","volume":"22","author":"Cicinelli","year":"2008","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0039","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1208\/s12249-017-0773-6","article-title":"The physicochemical investigation of 17\u03b2-estradiol crystalline prepared by in situ pH-dependent solubility technique with polyvinylpyrrolidone","volume":"18","author":"Xiong","year":"2017","journal-title":"AAPS PharmSciTech"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0040","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s11095-005-8418-y","article-title":"Design of estradiol loaded PLGA nanoparticulate formulations: a potential oral delivery system for hormone therapy","volume":"23","author":"Hariharan","year":"2006","journal-title":"Pharm Res"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0041","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1089\/jam.1999.12.27","article-title":"Inhalation of estradiol for sustained systemic delivery","volume":"12","author":"Wang","year":"1999","journal-title":"J Aerosol Med"},{"key":"10.1016\/j.xphs.2023.02.021_bib0042","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3389\/fnbeh.2020.597690","article-title":"Poly (lactic-co-glycolic acid) nanoparticle encapsulated 17\u03b2-estradiol improves spatial memory and increases uterine stimulation in middle-aged ovariectomized rats","volume":"14","author":"Prakapenka","year":"2020","journal-title":"Front Behav Neurosci"},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0043","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1080\/03639040500217624","article-title":"Biodegradable microparticulates of beta-estradiol: preparation and in vitro characterization","volume":"31","author":"Zaghloul","year":"2005","journal-title":"Drug Dev Ind Pharm"},{"issue":"12","key":"10.1016\/j.xphs.2023.02.021_bib0044","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1007\/s11095-016-2019-9","article-title":"Shape-memory terpolymer rods with 17-\u03b2-estradiol for the treatment of neurodegenerative diseases: an in vitro and in vivo study","volume":"33","author":"Turek","year":"2016","journal-title":"Pharm. Res."},{"key":"10.1016\/j.xphs.2023.02.021_bib0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.jddst.2021.102701","article-title":"Long-acting silk fibroin xerogel delivery systems for controlled release of estradiol","volume":"65","author":"Kri\u017eman","year":"2021","journal-title":"J Drug Delivery Sci Technol"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0046","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2165\/00137696-200301040-00003","article-title":"Intravaginal drug delivery systems","volume":"1","author":"Bernkop-Schn\u00fcrch","year":"2003","journal-title":"Am J Drug Delivery"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0047","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1592\/phco.21.5.464.34486","article-title":"Urogenital atrophy: prevention and treatment","volume":"21","author":"Willhite","year":"2001","journal-title":"Pharmacotherapy"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0048","doi-asserted-by":"crossref","first-page":"40","DOI":"10.14227\/DT250318P40","article-title":"Simulated genital tract fluids and their applicability in drug release\/dissolution testing of vaginal dosage forms","volume":"25","author":"Tietz","year":"2018","journal-title":"Dissolut Technol"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0049","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0010-7824(99)00010-4","article-title":"A vaginal fluid simulant","volume":"59","author":"Owen","year":"1999","journal-title":"Contraception"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0050","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0378-5122(94)00863-3","article-title":"The vaginal epithelium in the postmenopause\u2014cytology, histology and pH as methods of assessment","volume":"21","author":"Nilsson","year":"1995","journal-title":"Maturitas"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0051","doi-asserted-by":"crossref","first-page":"50","DOI":"10.55453\/rjmm.2022.125.1.7","article-title":"Vulvovaginal atrophy\u2013the impact on the quality of life and self-regard. Review of literature","volume":"125","author":"Turcan","year":"2022","journal-title":"Roman J Milit Med"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0052","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1089\/jwh.2016.6187","article-title":"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","volume":"26","author":"Constantine","year":"2017","journal-title":"J Women's Health"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0053","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/GME.0000000000001666","article-title":"Does age at the start of treatment for vaginal atrophy predict response to vaginal estrogen therapy? Post hoc analysis of data from a randomized clinical trial involving 205 women treated with 10 \u03bcg estradiol vaginal tablets","volume":"28","author":"Derzko","year":"2021","journal-title":"Menopause"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0054","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/GME.0000000000001443","article-title":"Physical characteristics and properties of estradiol softgel vaginal inserts","volume":"27","author":"Simon","year":"2020","journal-title":"Menopause"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0055","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3390\/pharmaceutics13020255","article-title":"In vitro\u2013in vivo correlation (IVIVC) population modeling for the in silico bioequivalence of a long-acting release formulation of progesterone","volume":"13","author":"Tosca","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.xphs.2023.02.021_bib0056","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejps.2021.105801","article-title":"Development and characterization of chitosan nanoparticles loaded nanofiber hybrid system for vaginal controlled release of benzydamine","volume":"161","author":"Tu\u011fcu-Demir\u00f6z","year":"2021","journal-title":"Eur J Pharm Sci"},{"issue":"7","key":"10.1016\/j.xphs.2023.02.021_bib0057","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.3390\/ma13071709","article-title":"Chitosan\/poly (2-ethyl-2-oxazoline) films with ciprofloxacin for application in vaginal drug delivery","volume":"13","author":"Abilova","year":"2020","journal-title":"Materials"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0058","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/SPV.0b013e3181ab4804","article-title":"Local effects of vaginally administered estrogen therapy: a review","volume":"15","author":"Krause","year":"2009","journal-title":"J Pelvic Med Surg"},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0059","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1111\/jog.14336","article-title":"Effect of estradiol vaginal gel on vaginal atrophy in postmenopausal women: a randomized double-blind controlled trial","volume":"46","author":"Tanmahasamut","year":"2020","journal-title":"J Obstet Gynaecol Res"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0060","first-page":"556","article-title":"Estradiol absorption from vaginal tablets in postmenopausal women","volume":"99","author":"Notelovitz","year":"2002","journal-title":"Obstet Gynecol"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0061","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0378-5122(92)90246-Z","article-title":"Low-dose oestradiol in the treatment of urogenital oestrogen deficiency\u2014a pharmacokinetic and pharmacodynamic study","volume":"15","author":"Nilsson","year":"1992","journal-title":"Maturitas"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0062","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0378-5122(94)00865-5","article-title":"Low-dose 17\u03b2-oestradiol during maintenance therapy\u2014a pharmacokinetic and pharmacodynamic study","volume":"21","author":"Nilsson","year":"1995","journal-title":"Maturitas"},{"key":"10.1016\/j.xphs.2023.02.021_bib0063","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2147\/IJWH.S41897","article-title":"Improved compliance and patient satisfaction with estradiol vaginal tablets in postmenopausal women previously treated with another local estrogen therapy","volume":"5","author":"Minkin","year":"2013","journal-title":"Int J Women's Health"},{"issue":"25","key":"10.1016\/j.xphs.2023.02.021_bib0064","article-title":"Modern management of genitourinary syndrome of menopause","volume":"10","author":"Da Silva","year":"2021","journal-title":"Fac Rev"},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0065","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/GME.0000000000001782","article-title":"Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women","volume":"28","author":"Jiang","year":"2021","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0066","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2147\/IJWH.S36026","article-title":"Overcoming resistance and barriers to the use of local estrogen therapy for the treatment of vaginal atrophy","volume":"4","author":"Chism","year":"2012","journal-title":"Int J Women's Health"},{"key":"10.1016\/j.xphs.2023.02.021_bib0067","unstructured":"Estrace Cream. Estradiol Vaginal Cream, USP, 0.01% [package insert]. Rockaway, NJ: Warner Chilcott, Inc. Available at: http:\/\/www.DailyMed-ESTRADIOLcream(nih.gov). Accessed 15 July 2022."},{"key":"10.1016\/j.xphs.2023.02.021_bib0068","first-page":"147","article-title":"Imvexxy-another estradiol vaginal insert for dyspareunia","volume":"60","author":"Abramowicz","year":"2018","journal-title":"Med Lett Drugs Ther"},{"key":"10.1016\/j.xphs.2023.02.021_bib0069","unstructured":"Vagifem Tablet. Estradiol Vaginal Tablets, [prescribing information]. Princeton, NJ: Novo Nordisk Inc. Available at: https:\/\/www.novo-pi.com\/vagifem.pdf. Accessed 12 June 2022."},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0070","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/GME.0000000000000786","article-title":"The REJOICE trial: a phase 3 randomized, controlled trial evaluating the safety and efficacy of a novel vaginal estradiol soft-gel capsule for symptomatic vulvar and vaginal atrophy","volume":"24","author":"Constantine","year":"2017","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0071","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1358\/dot.2018.54.11.2885879","article-title":"Estradiol vaginal inserts (Imvexxy): effective in genitourinary syndrome of menopause without increasing systemic estrogen levels","volume":"54","author":"Paton","year":"2018","journal-title":"Drugs Today"},{"issue":"9","key":"10.1016\/j.xphs.2023.02.021_bib0072","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1097\/GME.0000000000000880","article-title":"Visual improvements in vaginal mucosa correlate with symptoms of VVA: data from a double-blind, placebo-controlled trial","volume":"24","author":"Simon","year":"2017","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0073","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jconrel.2019.10.015","article-title":"In vitro release testing methods for drug-releasing vaginal rings","volume":"313","author":"Boyd","year":"2019","journal-title":"J Controlled Release"},{"issue":"07","key":"10.1016\/j.xphs.2023.02.021_bib0074","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1055\/a-1369-9395","article-title":"Development of hormonal intravaginal rings: technology and challenges","volume":"81","author":"Rafiei","year":"2021","journal-title":"Geburtshilfe Frauenheilkd"},{"key":"10.1016\/j.xphs.2023.02.021_bib0075","unstructured":"Estring. Estradiol Vaginal Ring, [prescribing information]. New York, NY: Pharmacia and Upjohn Company, Division of Pfizer Inc. Available at: https:\/\/www.pfizerpro.com\/sites\/default\/files\/estring_patient_education_brochure_pdf.pdf. Accessed 23 June 2022."},{"key":"10.1016\/j.xphs.2023.02.021_bib0076","unstructured":"Femring. Estradiol Acetate Vaginal Ring, [prescribing information]. East Hanover, NJ: Millicent Pharma Ltd. Available at: https:\/\/www.femring.com\/downloads\/New-Femring-USPI-and-PPI-Sept-2018.pdf. Accessed 28 June 2022."},{"issue":"11","key":"10.1016\/j.xphs.2023.02.021_bib0077","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1097\/GME.0000000000001220","article-title":"17\u03b2-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis","volume":"25","author":"Rioux","year":"2018","journal-title":"Menopause"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0078","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00404-010-1382-8","article-title":"The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial","volume":"283","author":"Ekin","year":"2011","journal-title":"Arch Gynecol Obstet"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0079","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1034\/j.1600-0412.2000.079004293.x","article-title":"Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy","volume":"79","author":"Dugal","year":"2000","journal-title":"Acta Obstet Gynecol Scand"},{"issue":"12","key":"10.1016\/j.xphs.2023.02.021_bib0080","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.4103\/1735-1995.172983","article-title":"A comparative study of vaginal estrogen cream and sustained-release estradiol vaginal tablet (Vagifem) in the treatment of atrophic vaginitis in Isfahan, Iran in 2010-2012","volume":"20","author":"Hosseinzadeh","year":"2015","journal-title":"J Res Med Sci"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0081","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/gme.0b013e31817b6132","article-title":"Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women","volume":"16","author":"Labrie","year":"2009","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0082","unstructured":"ClinicalTrials.gov. Study to Evaluate the Safety and Bioequivalence of Estradiol Vaginal Inserts, 10 mcg and Vagifem\u00ae 10 mcg and Compare to Placebo. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01779947. Accessed 15 July 2022."},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0083","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0028-2243(92)90059-8","article-title":"Low-dose 17\u03b2-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study","volume":"44","author":"Eriksen","year":"1992","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"10","key":"10.1016\/j.xphs.2023.02.021_bib0084","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1097\/GME.0000000000001131","article-title":"Effects of vaginal estradiol tablets and moisturizer on menopause-specific quality of life and mood in healthy post-menopausal women with vaginal symptoms: a randomized clinical trial","volume":"25","author":"Diem","year":"2018","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0085","series-title":"Design of an Intravaginal Composite Polymeric System for the Reduction and Prevention of STI and HIV Transmission","author":"Mashingaidze","year":"2014"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0086","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1080\/13697137.2019.1577379","article-title":"TX-004HR clinically improves symptoms of vulvar and vaginal atrophy in postmenopausal women","volume":"22","author":"Simon","year":"2019","journal-title":"Climacteric"},{"issue":"9","key":"10.1016\/j.xphs.2023.02.021_bib0087","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1097\/GME.0000000000001801","article-title":"Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert","volume":"28","author":"Mirkin","year":"2021","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0088","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s001920050040","article-title":"Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: a comparative and a placebo-controlled multicenter study","volume":"10","author":"Casper","year":"1999","journal-title":"Int Urogynecol J"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0089","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0301-2115(96)02612-7","article-title":"Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy","volume":"71","author":"Barentsen","year":"1997","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0090","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/13697130500087016","article-title":"Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet","volume":"8","author":"Weisberg","year":"2005","journal-title":"Climacteric"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0091","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/0002-9378(94)90074-4","article-title":"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","volume":"171","author":"Henriksson","year":"1994","journal-title":"Am J Obstet Gynecol"},{"key":"10.1016\/j.xphs.2023.02.021_bib0092","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1471-0528.1996.tb09741.x","article-title":"A comparative study of low dose oestradiol safety and efficacy of continuous released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy","volume":"103","author":"Ayton","year":"1996","journal-title":"Br J Obstet Gynaecol"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0093","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/S0002-9378(99)70597-1","article-title":"A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women","volume":"180","author":"Eriksen","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"10.1016\/j.xphs.2023.02.021_bib0094","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0378-5122(93)90059-Q","article-title":"Oestradiol-releasing vaginal ring for treatment of postmenopausal urogenital atrophy","volume":"16","author":"Smith","year":"1993","journal-title":"Maturitas"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0095","first-page":"823","article-title":"Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms","volume":"102","author":"Speroff","year":"2003","journal-title":"Obstet Gynecol"},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0096","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1471-0528.2003.02408.x","article-title":"The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women","volume":"110","author":"Buckler","year":"2003","journal-title":"BJOG"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0097","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0378-5122(96)01087-0","article-title":"Transdermal estrogen with a levonorgestrel-releasing intrauterine device for climacteric complaints versus estradiol-releasing vaginal ring with a vaginal progesterone suppository: clinical and endometrial responses","volume":"26","author":"Antoniou","year":"1997","journal-title":"Maturitas"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0098","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/gye.17.3.247.254","article-title":"Estradiol\/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women","volume":"17","author":"Hamada","year":"2003","journal-title":"Gynecol Endocrinol"},{"issue":"24","key":"10.1016\/j.xphs.2023.02.021_bib0099","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1001\/jama.1979.03300240039024","article-title":"Systemic absorption and sustained effects of vaginal estrogen creams","volume":"242","author":"Martin","year":"1979","journal-title":"Jama"},{"key":"10.1016\/j.xphs.2023.02.021_bib0100","unstructured":"ClinicalTrials.gov. Study to Evaluate Equivalence of Estradiol Vaginal Cream 0.01% to Estrace\u00ae Cream 0.01% in Atrophic Vaginitis. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT03294538. Accessed 25 July 2022."},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0101","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/GME.0000000000000985","article-title":"A randomized, multicenter, double-blind study to evaluate the safety and efficacy of estradiol vaginal cream 0.003% in postmenopausal women with dyspareunia as the most bothersome symptom","volume":"25","author":"Kroll","year":"2018","journal-title":"Menopause"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0102","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4314\/tjpr.v9i4.58924","article-title":"Bioadhesive controlled release clotrimazole vaginal tablets","volume":"9","author":"Bhat","year":"2010","journal-title":"Trop J Pharm Res"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0103","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0731-7085(03)00501-6","article-title":"Development and validation of a reversed-phase liquid chromatographic method for analysis of degradation products of estradiol in Vagifem\u00ae tablets","volume":"34","author":"Nygaard","year":"2004","journal-title":"J Pharm Biomed Anal"},{"issue":"sup1","key":"10.1016\/j.xphs.2023.02.021_bib0104","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3109\/13697137.2013.807606","article-title":"Ultra-low-dose vaginal estrogen tablets for the treatment of postmenopausal vaginal atrophy","volume":"16","author":"Simon","year":"2013","journal-title":"Climacteric"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0105","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1258\/mi.2012.011120","article-title":"Treatment of postmenopausal vaginal atrophy with 10-\u00b5g estradiol vaginal tablets","volume":"18","author":"Panay","year":"2012","journal-title":"Menopause Int"},{"key":"10.1016\/j.xphs.2023.02.021_bib0106","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2147\/IJWH.S52555","article-title":"Reviewing the options for local estrogen treatment of vaginal atrophy","volume":"6","author":"Lindahl","year":"2014","journal-title":"Int J Women's Health"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12905-020-01099-y","article-title":"Multiple use applicator for vaginal tablets\/vaginal inserts: compliance verification and suitability studies","volume":"20","author":"Brunner","year":"2020","journal-title":"BMC Women's Health"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0108","first-page":"415","article-title":"Vagifem is superior to vaginal Premarin in induction of endometrial thickness in the frozen-thawed cycle patients with refractory endometria: a randomized clinical trial","volume":"12","author":"Zolghadri","year":"2014","journal-title":"Iran J Reprod Med"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0109","first-page":"182","article-title":"Update in female hormonal therapy: what the urologist should know: NYU case of the month, december 2020","volume":"22","author":"Rosenblum","year":"2020","journal-title":"Rev Urol"},{"issue":"11","key":"10.1016\/j.xphs.2023.02.021_bib0110","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1080\/17425247.2020.1810662","article-title":"Estradiol softgel inserts for the treatment of VVA symptoms: an expert opinion","volume":"17","author":"Liu","year":"2020","journal-title":"Expert Opin Drug Delivery"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0111","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0009-9236(98)90154-0","article-title":"The use of two estrogen preparations (a combined contraceptive pill versus conjugated estrogen cream) intravaginally to treat urogenital symptoms in postmenopausal Thai women: a comparative study","volume":"64","author":"Chompootaweep","year":"1998","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0112","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1080\/01443615.2021.2006163","article-title":"Genitourinary syndrome, local oestrogen therapy and endometrial pathology: a single-centre, randomised study","volume":"42","author":"Kovachev","year":"2022","journal-title":"J Obstet Gynaecol"},{"key":"10.1016\/j.xphs.2023.02.021_bib0113","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2147\/MDER.S265824","article-title":"Safety and effiacy of an oxytocin gel and an equivalent gel but without hormonal ingredients (Vagivital\u00ae Gel) in postmenopausal women with symptoms of vulvovaginal atrophy: a randomized, double-blind controlled study","volume":"13","author":"Jonasson","year":"2020","journal-title":"Med Devices Evid Res"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0114","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1097\/AOG.0b013e3181f386bb","article-title":"Endometrial safety of ultra-low-dose estradiol vaginal tablets","volume":"116","author":"Simon","year":"2010","journal-title":"Obstet Gynecol"},{"key":"10.1016\/j.xphs.2023.02.021_bib0115","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0378-5122(91)90144-F","article-title":"Long-term treatment of atrophic vaginitis with low-dose oestradiol vaginal tablets","volume":"14","author":"Mettler","year":"1991","journal-title":"Maturitas"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0116","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/annonc\/mdj127","article-title":"Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors","volume":"17","author":"Kendall","year":"2006","journal-title":"Ann Oncol"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0117","first-page":"12","article-title":"A comparative study of vaginal estrogen cream and sustained-released estradiol vaginal tablet (vagifem) in the treatment of atrophic vaginitis among postmenopausal women","volume":"12","author":"Daneshmand","year":"2014","journal-title":"Int J Reprod Biomed"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0118","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1089\/jwh.2007.0407","article-title":"A retrospective managed care claims data analysis of medication adherence to vaginal estrogen therapy: implications for clinical practice","volume":"17","author":"Shulman","year":"2008","journal-title":"J Women's Health"},{"key":"10.1016\/j.xphs.2023.02.021_bib0119","unstructured":"ClinicalTrials.gov. To Study Generic Estradiol 10 mcg Vaginal Tablets in the Treatment of Vulvar and Vaginal Atrophy in Post Menopausal Women. Available online at: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02668796. Accessed 15 July 2022."},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0120","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1097\/GME.0000000000000848","article-title":"Patient acceptability and satisfaction with a low-dose solubilized vaginal estradiol softgel capsule, TX-004HR","volume":"24","author":"Kingsberg","year":"2017","journal-title":"Menopause"},{"key":"10.1016\/j.xphs.2023.02.021_bib0121","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.maturitas.2017.02.008","article-title":"A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: efficacy and pharmacokinetic data review","volume":"99","author":"Simon","year":"2017","journal-title":"Maturitas"},{"issue":"12","key":"10.1016\/j.xphs.2023.02.021_bib0122","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1080\/03007995.2018.1527578","article-title":"Estradiol vaginal inserts (4 \u00b5g and 10 \u00b5g) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic data","volume":"34","author":"Constantine","year":"2018","journal-title":"Curr Med Res Opin"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0123","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3109\/13697137.2015.1136926","article-title":"Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule","volume":"19","author":"Pickar","year":"2016","journal-title":"Climacteric"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0124","first-page":"1","article-title":"Updates on therapeutic alternatives for genitourinary syndrome of menopause: hormonal and non-hormonal managements","volume":"27","author":"Shim","year":"2021","journal-title":"JMM"},{"key":"10.1016\/j.xphs.2023.02.021_bib0125","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.contraception.2021.10.001","article-title":"Vaginal ring acceptability: a systematic review and meta-analysis of vaginal ring experiences from around the world","volume":"106","author":"Ridgeway","year":"2022","journal-title":"Contraception"},{"key":"10.1016\/j.xphs.2023.02.021_bib0126","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1016\/S0142-9612(02)00086-8","article-title":"A dynamic mechanical method for determining the silicone elastomer solubility of drugs and pharmaceutical excipients in silicone intravaginal drug delivery rings","volume":"23","author":"Malcolm","year":"2002","journal-title":"Biomaterials"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0127","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0002-9378(98)70558-7","article-title":"The clinical platform for the 17\u03b2-estradiol vaginal releasing ring","volume":"178","author":"Bachmann","year":"1998","journal-title":"Am J Obstet Gynecol"},{"issue":"12","key":"10.1016\/j.xphs.2023.02.021_bib0128","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2165\/00002512-200421120-00001","article-title":"Vaginal rings for menopausal symptom relief","volume":"21","author":"Ballagh","year":"2004","journal-title":"Drugs aging"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0129","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0002-9378(96)70378-2","article-title":"A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging","volume":"174","author":"Henriksson","year":"1996","journal-title":"Am J Obstet Gynecol"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0130","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/ejc.8.4.217.224","article-title":"Low-dose intravaginal estradiol delivery using a Silastic vaginal ring for estrogen replacement therapy in postmenopausal women: a review","volume":"8","author":"Sarkar","year":"2003","journal-title":"Eur J Contracept Reprod Health Care"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0131","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1080\/cmt.6.2.118.127","article-title":"Comparison of a novel vaginal ring delivering estradiol acetate versus oral estradiol for relief of vasomotor menopausal symptoms","volume":"6","author":"Al-Azzawi","year":"2003","journal-title":"Climacteric"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0132","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/01.GME.0000163870.03388.4D","article-title":"Bone mineral density in postmenopausal women treated with a vaginal ring delivering systemic doses of estradiol acetate","volume":"12","author":"Al-Azzawi","year":"2005","journal-title":"Menopause"},{"issue":"10","key":"10.1016\/j.xphs.2023.02.021_bib0133","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1089\/jwh.2008.1281","article-title":"Vaginal estrogen therapy for the treatment of atrophic vaginitis","volume":"18","author":"Lynch","year":"2009","journal-title":"J Women's Health"},{"key":"10.1016\/j.xphs.2023.02.021_bib0134","first-page":"1","article-title":"Color, scent and size: exploring women's preferences around design characteristics of drug-releasing vaginal rings","author":"Zhao","year":"2022","journal-title":"AIDS and Behav"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0135","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0378-5122(96)01072-9","article-title":"Estradiol delivery by vaginal rings: potential for hormone replacement therapy","volume":"26","author":"Nash","year":"1997","journal-title":"Maturitas"},{"issue":"6","key":"10.1016\/j.xphs.2023.02.021_bib0136","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/S0002-9378(99)70383-2","article-title":"Estradiol-delivering vaginal rings for hormone replacement therapy","volume":"181","author":"Nash","year":"1999","journal-title":"Am J Obstet Gynecol"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0137","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/S0015-0282(02)03365-4","article-title":"Vaginal rings delivering progesterone and estradiol may be a new method of hormone replacement therapy","volume":"78","author":"Maruo","year":"2002","journal-title":"Fertil Steril"},{"issue":"8","key":"10.1016\/j.xphs.2023.02.021_bib0138","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1016\/j.xphs.2019.03.032","article-title":"Pharmacokinetics and tolerability of a novel 17\u03b2-Estradiol and progesterone intravaginal ring in sheep","volume":"108","author":"Weiss","year":"2019","journal-title":"J Pharm Sci"},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0139","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1208\/s12249-013-9989-2","article-title":"Polydimethylsiloxane\u2013Indomethacin blends and nanoparticles","volume":"14","author":"Racles","year":"2013","journal-title":"AAPS PharmSciTech"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0140","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/jps.10300","article-title":"Estradiol\u2013progesterone interaction during the preparation of vaginal rings","volume":"92","author":"Saleh","year":"2003","journal-title":"J Pharm Sci"},{"issue":"5","key":"10.1016\/j.xphs.2023.02.021_bib0141","doi-asserted-by":"crossref","first-page":"751","DOI":"10.3390\/pharmaceutics13050751","article-title":"The vaginal microbiota, bacterial biofilms and polymeric drug-releasing vaginal rings","volume":"13","author":"Carson","year":"2021","journal-title":"Pharmaceutics"},{"issue":"2","key":"10.1016\/j.xphs.2023.02.021_bib0142","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0168-3659(03)00178-0","article-title":"Influence of silicone elastomer solubility and diffusivity on the in vitro release of drugs from intravaginal rings","volume":"90","author":"Malcolm","year":"2003","journal-title":"J Controlled Release"},{"key":"10.1016\/j.xphs.2023.02.021_bib0143","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0378-5122(89)90120-5","article-title":"Vaginal rings for continuous low-dose release of oestradiol in the treatment of urogenital atrophy","volume":"11","author":"Holmgren","year":"1989","journal-title":"Maturitas"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0144","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1210\/jcem-54-1-208","article-title":"Development of a vaginal ring for achieving physiologic levels of 17\u03b2-estradi0l in hypoestrogenic women","volume":"54","author":"Stumpf","year":"1982","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"10.1016\/j.xphs.2023.02.021_bib0145","first-page":"1330","article-title":"Vaginal drug delivery system a promising approach for antiretroviral drug in the prevention of HIV infection: a review","volume":"8","author":"Rahman","year":"2016","journal-title":"J Pharm Sci Res"},{"key":"10.1016\/j.xphs.2023.02.021_bib0146","unstructured":"ClinicalTrials.gov. Study to Evaluate the Equivalence of Estradiol Vaginal Cream to Reference Standard in the Treatment of Vaginal Atrophy. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/results\/NCT03332303. Accessed 29 July 2022."},{"key":"10.1016\/j.xphs.2023.02.021_bib0147","unstructured":"ClinicalTrials.gov. A Study Comparing Estradiol Vaginal Cream to Estrace\u00ae Cream in Females with Atrophic Vaginitis. Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT02995694. Accessed 29 July 2022."},{"key":"10.1016\/j.xphs.2023.02.021_bib0148","unstructured":"ClinicalTrials.gov. A comparison of Estradiol Vaginal Cream to Estrace\u00ae Cream in 350 Postmenopausal Females with Atrophic Vaginitis. Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02195986. Accessed 29 July 2022."},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0149","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1056\/NEJM197801262980406","article-title":"Absroption of estrogens from vaginal creams","volume":"298","author":"Rigg","year":"1978","journal-title":"N Engl J Med"},{"key":"10.1016\/j.xphs.2023.02.021_bib0150","unstructured":"European Medicines Agency. Estradiol-Containing (0.01% w\/w) Medicinal Products For Topical Use. Available at: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/estradiol-containing-001-ww-medicinal-products-topical-use. Accessed 20 July 2022."},{"issue":"3","key":"10.1016\/j.xphs.2023.02.021_bib0151","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/00042192-200205000-00006","article-title":"Treatment of urogenital atrophy with low-dose estradiol: preliminary results","volume":"9","author":"Santen","year":"2002","journal-title":"Menopause"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0152","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/SPV.0000000000000256","article-title":"Combined tolterodine and vaginal estradiol cream for overactive bladder symptoms after randomized single-therapy treatment","volume":"22","author":"Ellington","year":"2016","journal-title":"Female Pelvic Med Reconstr Surg"},{"issue":"4","key":"10.1016\/j.xphs.2023.02.021_bib0153","first-page":"248","article-title":"Satisfaction on the use of a transdermal spray containing 1.53 mg estradiol for the treatment of symptoms associated with menopause","volume":"1","author":"\u00c1guas","year":"2020","journal-title":"Gynecol Reprod Endocrinol Metabol"},{"issue":"1","key":"10.1016\/j.xphs.2023.02.021_bib0154","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2217\/17455057.5.1.23","article-title":"Low-dose estradiol spray: a novel treatment for vasomotor instability in postmenopausal women","volume":"5","author":"Buster","year":"2009","journal-title":"Women's Health"}],"container-title":["Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354923000734?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354923000734?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T09:41:00Z","timestamp":1758361260000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022354923000734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":154,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["S0022354923000734"],"URL":"https:\/\/doi.org\/10.1016\/j.xphs.2023.02.021","relation":{},"ISSN":["0022-3549"],"issn-type":[{"value":"0022-3549","type":"print"}],"subject":[],"published":{"date-parts":[[2023,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Intravaginal Drug Delivery Systems to Treat the Genitourinary Syndrome of Menopause: Towards the Design of Safe and Efficacious Estrogen-loaded Prototypes","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xphs.2023.02.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}