{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T03:51:10Z","timestamp":1773373870285,"version":"3.50.1"},"reference-count":28,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T00:00:00Z","timestamp":1487203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","maturitas.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Maturitas"],"published-print":{"date-parts":[[2017,5]]},"DOI":"10.1016\/j.maturitas.2017.02.008","type":"journal-article","created":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T03:32:00Z","timestamp":1487215920000},"page":"51-58","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"C","title":["A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: Efficacy and pharmacokinetic data review"],"prefix":"10.1016","volume":"99","author":[{"given":"James A.","family":"Simon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F.","family":"Archer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ginger D.","family":"Constantine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H.","family":"Pickar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia M.","family":"Amadio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Bernick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelli","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Mirkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.maturitas.2017.02.008_bib0005","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1097\/GME.0000000000000329","article-title":"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","volume":"21","author":"Portman","year":"2014","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0010","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."},{"key":"10.1016\/j.maturitas.2017.02.008_bib0015","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1097\/GME.0b013e318287342d","article-title":"Vaginal health in the United States: results from the vaginal health: insights, views & attitudes survey","volume":"20","author":"Simon","year":"2013","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0020","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.maturitas.2004.06.019","article-title":"Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative","volume":"49","author":"Pastore","year":"2004","journal-title":"Maturitas"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0025","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1111\/jsm.12190","article-title":"Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Women's VIews of Treatment Options for Menopausal Vaginal ChangEs) survey","volume":"10","author":"Kingsberg","year":"2013","journal-title":"J. Sex. Med."},{"key":"10.1016\/j.maturitas.2017.02.008_bib0030","first-page":"351","article-title":"A prospective population-based study of menopausal symptoms","volume":"96","author":"Dennerstein","year":"2000","journal-title":"Obstet. Gynecol."},{"issue":"20","key":"10.1016\/j.maturitas.2017.02.008_bib0035","first-page":"888","article-title":"Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society","year":"2013","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0040","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4137\/CMRH.S14498","article-title":"Management of vaginal atrophy: implications from the REVIVE study","volume":"8","author":"Wysocki","year":"2014","journal-title":"Clin. Med. Insights Reprod. Health"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0045","series-title":"Age and Sex Composition: 2010 Census Briefs. Issued May","author":"Census Bureau","year":"2011"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0050","article-title":"The REJOICE trial: a phase 3 randomized, controlled trial evaluating the safety and efficacy of a novel vaginal estradiol softgel capsule for symptomatic vulvar and vaginal atrophy (VVA)","author":"Constantine","year":"2016","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0055","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"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0060","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.maturitas.2017.02.008_bib0065","article-title":"TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol","author":"Archer","year":"2016","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0070","unstructured":"Data on file. TherapeuticsMD. Boca Raton, FL."},{"key":"10.1016\/j.maturitas.2017.02.008_bib0075","series-title":"Vagifem\u00ae (estradiol Vaginal Tablets) Prescribing Information","year":"2012"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0080","series-title":"NAMS Annual Meeting","article-title":"The effect of body position on the pharmacokinetics of TX-004HR, estradiol vaginal softgel capsule","author":"Constantine","year":"2016"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0085","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1210\/jcem-39-6-1020","article-title":"Endocrine function of the postmenopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood","volume":"39","author":"Judd","year":"1974","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.maturitas.2017.02.008_bib0090","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0378-5122(94)00869-9","article-title":"A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density","volume":"21","author":"Rannevik","year":"1995","journal-title":"Maturitas"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0095","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\u2013a pharmacokinetic and pharmacodynamic study","volume":"15","author":"Nilsson","year":"1992","journal-title":"Maturitas"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0100","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/gme.0b013e3181a48c4e","article-title":"Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally","volume":"16","author":"Bachmann","year":"2009","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0105","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1097\/gme.0b013e318199e734","article-title":"Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy","volume":"16","author":"Freedman","year":"2009","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0110","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1097\/AOG.0b013e31818aa7c3","article-title":"Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet","volume":"112","author":"Simon","year":"2008","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.maturitas.2017.02.008_bib0115","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1097\/01.AOG.0000296714.12226.0f","article-title":"Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial","volume":"111","author":"Bachmann","year":"2008","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.maturitas.2017.02.008_bib0120","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/gme.0b013e318279ba64","article-title":"a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy","volume":"20","author":"Portman","year":"2013","journal-title":"Menopause"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0125","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.maturitas.2014.02.015","article-title":"a non-oestrogen selective oestrogen receptor modulator for the treatment of vaginal dryness associated with postmenopausal vulvar and vaginal atrophy: a randomised, placebo-controlled, phase III trial","volume":"78","author":"Portman","year":"2014","journal-title":"Maturitas"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0130","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"},{"key":"10.1016\/j.maturitas.2017.02.008_bib0135","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1097\/AOG.0000000000001351","article-title":"The use of vaginal estrogen in women with a history of estrogen-dependent breast cancer. Committee Opinion No. 659. American College of Obstetricians and Gynecologist. American College of Obstetricians and Gynecologists","volume":"127","year":"2016","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.maturitas.2017.02.008_bib0140","doi-asserted-by":"crossref","DOI":"10.1097\/GME.0000000000000848","article-title":"Patient acceptability and satisfaction with a low-dose solubilized vaginal estradiol softgel capsule, TX-004HR","author":"Kingsberg","year":"2017","journal-title":"Menopause"}],"container-title":["Maturitas"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S037851221630398X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S037851221630398X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T09:09:37Z","timestamp":1759914577000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S037851221630398X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":28,"alternative-id":["S037851221630398X"],"URL":"https:\/\/doi.org\/10.1016\/j.maturitas.2017.02.008","relation":{},"ISSN":["0378-5122"],"issn-type":[{"value":"0378-5122","type":"print"}],"subject":[],"published":{"date-parts":[[2017,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: Efficacy and pharmacokinetic data review","name":"articletitle","label":"Article Title"},{"value":"Maturitas","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.maturitas.2017.02.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 The Authors. Published by Elsevier Ireland Ltd.","name":"copyright","label":"Copyright"}]}}