{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:02:53Z","timestamp":1792270973220,"version":"4.4.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":538,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>The levels of circulating follicle-stimulating hormone, luteinizing hormone, estriol, estradiol, and estrone remained unchanged after a 12-week treatment with 0.005% estriol vaginal gel in postmenopausal women receiving nonsteroidal aromatase inhibitors for hormone receptor-positive early breast cancer. These results support the safety of 0.005% estriol vaginal gel for the treatment of bothering symptoms of vulvovaginal atrophy in breast cancer survivors. The results provide clinicians with confidence in the use of this product in women who do not experience symptom relief with nonhormonal remedies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Symptoms of vulvovaginal atrophy associated with treatment with nonsteroidal aromatase inhibitors (NSAIs) negatively impact patients\u2019 quality of life and may affect adherence to NSAIs. Vaginal estrogens effectively improve these symptoms, although their safe use in breast cancer survivors remains unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Postmenopausal women with hormone receptor-positive early breast cancer receiving NSAI and moderate-to-severe vaginal dryness were randomized to 0.005% estriol vaginal gel or placebo for 12\u2009weeks. Circulating estrogens, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed at baseline and at weeks 1, 3, 8, and 12. The primary safety outcome was the variation in serum FSH from baseline to week 12.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Sixty-one women (mean age, 59\u2009years) enrolled in the study. Small oscillations were observed in FSH and LH, although they were always maintained within the postmenopausal range. No significant differences were found in the variation of FSH and LH between baseline and week 12 from the physiological variation observed before treatment. Women receiving 0.005% estriol vaginal gel had slightly increased estriol levels at weeks 1 and 3, with a subsequent reduction until normalizing at week 12; estradiol and estrone remained the below limit-of-quantitation in almost all samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Ultralow-dose 0.005% estriol vaginal gel did not significantly influence estrogens, FSH, and LH levels in women with breast cancer receiving NSAI. A transient negligible absorption of estriol and a nonsignificant variation of FSH after 12\u2009weeks were observed. These findings provide confidence for the safe use of 0.005% estriol vaginal gel in women with breast cancer with an indication for treatment with vaginal estrogens.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2020-0417","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T09:18:49Z","timestamp":1590571129000},"page":"e1846-e1854","source":"Crossref","is-referenced-by-count":32,"title":["A Phase II Prospective, Randomized, Double-Blind, Placebo-Controlled and Multicenter Clinical Trial to Assess the Safety of 0.005% Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women with Early Stage Breast Cancer in Treatment with Aromatase Inhibitor in the Adjuvant Setting"],"prefix":"10.1093","volume":"25","author":[{"given":"Pedro","family":"S\u00e1nchez-Rovira","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario de Ja\u00e9n, Ja\u00e9n, Spain"},{"name":"GEICAM Spanish Breast Cancer Group, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica Lind\u00e9n","family":"Hirschberg","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Karolinska Institute and Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gil-Gil","sequence":"additional","affiliation":[{"name":"GEICAM Spanish Breast Cancer Group, Spain"},{"name":"Breast Cancer Unit, Institut Catal\u00e0 d'Oncologia, IDIBELL, Hospitalet, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Bermejo-De Las Heras","sequence":"additional","affiliation":[{"name":"GEICAM Spanish Breast Cancer Group, Spain"},{"name":"Hospital Cl\u00ednico Universitario de Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Nieto-Magro","sequence":"additional","affiliation":[{"name":"Medical Department, Italfarmaco, SA, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"2021122511343061800_onco13381-bib-0001","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1177\/1758834016687260","article-title":"A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy","volume":"9","author":"Sousa","year":"2017","journal-title":"Ther Adv Med Oncol"},{"key":"2021122511343061800_onco13381-bib-0002","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.clbc.2015.06.005","article-title":"Genitourinary syndrome of menopause in breast cancer survivors: Are we facing new and safe hopes?","volume":"15","author":"Biglia","year":"2015","journal-title":"Clin 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