{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T20:43:24Z","timestamp":1785789804924,"version":"3.56.0"},"reference-count":16,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Women's Health"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Vulvovaginal atrophy (VVA) is characterized by vaginal\/vulvar dryness, irritation, dyspareunia, or dysuria. The objective of this study was to examine the efficacy and safety of a very low-dose estradiol vaginal cream (0.003%) applied twice per week in postmenopausal women with VVA-related vaginal dryness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>In this phase 3, randomized, double-blind, placebo-controlled, multicenter study, postmenopausal women with moderate\u2013severe vaginal dryness as the most bothersome VVA symptom were randomized (1:1) to estradiol cream 0.003% (15\u2009\u03bcg estradiol; 0.5\u2009g cream) or placebo (0.5\u2009g cream). Treatments were applied vaginally once daily for 2 weeks followed by two applications\/week for 10 weeks. Coprimary outcomes were changes in severity of vaginal dryness, percentage of vaginal superficial and parabasal cells, and vaginal pH at final assessment. Additional outcomes comprised changes in severity of other VVA signs and symptoms. Adverse events (AEs) were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Of the 576 randomized participants, most were white and had an average age of 59 years. At final assessment, estradiol reduced vaginal dryness severity, decreased vaginal pH, increased superficial cell percentage, and decreased parabasal cell percentage versus placebo (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009\u2264\u20090.05, all). Estradiol also reduced vaginal dryness severity at Weeks 4\u201312 and dyspareunia at Week 8 versus placebo (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009\u2264\u20090.05, all). Improvements in vaginal\/vulvar irritation\/itching severity and dysuria were similar between estradiol and placebo. Estradiol had comparable rates of treatment-emergent AEs to placebo. No deaths occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Very low-dose estradiol vaginal cream (0.003%) dosed twice weekly is an effective and well-tolerated treatment for VVA symptoms and dryness associated with menopause.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jwh.2017.6515","type":"journal-article","created":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T16:48:28Z","timestamp":1512146908000},"page":"231-237","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":42,"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"],"prefix":"10.1177","volume":"27","author":[{"given":"David F.","family":"Archer","sequence":"first","affiliation":[{"name":"Eastern Virginia Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Kimble","sequence":"additional","affiliation":[{"name":"Eastern Virginia Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.D. Yuhua","family":"Lin","sequence":"additional","affiliation":[{"name":"Allergan plc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Battucci","sequence":"additional","affiliation":[{"name":"Allergan plc","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilma","family":"Sniukiene","sequence":"additional","affiliation":[{"name":"Allergan plc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"Liu","sequence":"additional","affiliation":[{"name":"University Hospitals Cleveland Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000000329"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2016.07.045"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12190"},{"key":"e_1_3_3_5_2","first-page":"338","article-title":"Practice guidelines: ACOG releases clinical guidelines on management of menopausal symptoms","volume":"90","author":"American Family Physician","year":"2014","unstructured":"American Family Physician, eds. Practice guidelines: ACOG releases clinical guidelines on management of menopausal symptoms. Am Fam Physician, 2014; 90:338\u2013340.","journal-title":"Am Fam Physician"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000000921"},{"key":"e_1_3_3_7_2","unstructured":"US Food and drug Administration. Industry Guidance: Estrogen and estrogen\/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms\u2014Recommendations for clinical evaluation. Rockville MD: US Department of Health and Human Services 2003."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3109\/13697137.2014.947254"},{"key":"e_1_3_3_9_2","unstructured":"Estrace\u00ae (estradiol USP 0.01% vaginal cream). US prescribing information. Allergan USA Inc Irvine CA 2015. Available at: www.allergan.com\/assets\/pdf\/estrace_pi Accessed November20 2017."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2307\/2530051"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000526"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3109\/13697137.2012.756466"},{"key":"e_1_3_3_13_2","unstructured":"Premarin\u00ae (conjugated estrogens vaginal cream).. US prescribing information. Philadelphia PA: Wyeth Pharmaceuticals Inc. subsidiary of Pfizer 2014."},{"key":"e_1_3_3_14_2","unstructured":"Vagifem\u00ae (estradiol vaginal inserts).. US prescribing information. Plainsboro NJ: Novo Nordisk Inc 2016."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050100"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep24380"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.5.1.180-191.2006"}],"container-title":["Journal of Women's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/jwh.2017.6515","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jwh.2017.6515","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jwh.2017.6515","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:47:10Z","timestamp":1777657630000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/jwh.2017.6515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1089\/jwh.2017.6515"],"URL":"https:\/\/doi.org\/10.1089\/jwh.2017.6515","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.732205563.793582607","asserted-by":"object"}]},"ISSN":["1540-9996","1931-843X"],"issn-type":[{"value":"1540-9996","type":"print"},{"value":"1931-843X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3]]}}}