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Secondary objectives included assessing the effects of therapy on vaginal atrophy, quality of life (QoL) and menopause-related symptoms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>20 postmenopausal patients undergoing adjuvant letrozole therapy and experiencing VVA symptoms were treated with vaginal estradiol for 12\u00a0weeks. Gynecologic examination and symptom screening were conducted at baseline and after 12\u00a0weeks. Serum E2 levels were analyzed at baseline, and at two, four, eight, and 12\u00a0weeks. E2 levels were measured using both a routine liquid chromatography-tandem mass spectrometry (LC\u2013MS\/MS) method and a highly sensitive (hsE2-MS) LC\u2013MS\/MS method.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>At baseline, serum E2 levels, measured with hsE2-MS, were below the lower limit of quantification (LLOQ) in all patients. E2 remained below LLOQ throughout the treatment period in three patients (15%). Persistent E2 elevation above LLOQ was observed in six patients (30%), while isolated E2 elevations occurred in 10 patients (50%). One patient experienced transient E2 elevation in two sporadic measurements. Serum E2 variations were shown by using both LC\u2013MS\/MS methods. Vaginal pH, vaginal maturation index (VMI), and VVA symptoms significantly improved during treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Intravaginal estradiol therapy (10ug) during adjuvant letrozole resulted in transient increases in systemic E2 levels among early BC patients with VVA. Highly sensitive LC\u2013MS\/MS is a promising method for monitoring E2 levels during aromatase inhibitor (AI) therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10549-024-07564-8","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T04:03:11Z","timestamp":1735272191000},"page":"295-305","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of vaginal estrogen on serum estradiol during aromatase inhibitor therapy in breast cancer patients with vulvovaginal atrophy: a prospective trial"],"prefix":"10.1007","volume":"210","author":[{"given":"M\u00e1ria","family":"Faltinov\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Vehmanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heli","family":"Lyytinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Savolainen-Peltonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni","family":"Virtanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Haanp\u00e4\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aila","family":"Tiitinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Mattson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"issue":"5","key":"7564_CR1","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1200\/JCO.18.01160","volume":"37","author":"HJ Burstein","year":"2019","unstructured":"Burstein HJ, Lacchetti C, Anderson H, Buchholz TA, Davidson NE, Gelmon KA, Giordano SH, Hudis CA, Solky AJ, Stearns V et al (2019) Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. 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Approval was obtained from the Ethics committee of Helsinki University Hospital on April 20, 2020. The trial is registered in the Helsinki and Uusimaa Hospital District Clinical Trials Register (EudraCT Number 2019\u2013001234-34).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all participants included in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors confirm that this manuscript does not contain any individual person\u2019s data in any form.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}}]}}