{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:53:03Z","timestamp":1773391983802,"version":"3.50.1"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hormone replacement therapy (HRT) is widely prescribed for managing menopausal symptoms, yet its effects on the endometrium remain clinically important. While large-scale studies have established that estrogen-only HRT increases endometrial cancer risk and continuous combined regimens reduce this risk, real-world data on endometrial histology remain valuable for understanding contemporary practice patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective analysis of women who underwent hysteroscopy with endometrial sampling at Princess Royal University Hospital. Of the 62 patients, we included 24 (38.7%) with explicitly documented HRT status, excluding 38 (61.3%) whose HRT status was unknown or inadequately documented. We characterized HRT regimens by type, route, schedule, and duration when available. Histological findings were compared between HRT users (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f13) and non-users (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f11) using Fisher\u2019s exact test and Mann\u2013Whitney U tests.\n                      <jats:italic>Post-hoc<\/jats:italic>\n                      power calculations quantified the study\u2019s ability to detect clinically meaningful differences.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 24 patients (mean age 57.3\u202f\u00b1\u202f6.8\u202fyears), 13 (54.2%) received HRT, and 11 (45.8%) did not. HRT regimens included combined estrogen\u2013progestogen therapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f9, 69.2%), estrogen-only therapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f2, 15.4%), and unspecified formulations (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f2, 15.4%). Routes included transdermal (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f5, 38.5%), oral (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f4, 30.8%), and unspecified or mixed (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f4, 30.8%). Among combined users, continuous combined regimens were most common (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f5, 55.6%). No endometrial hyperplasia or carcinoma was identified in either group. Normal endometrium was most common in both HRT users (7\/13, 53.8%) and non-users (8\/11, 72.7%). No significant differences were observed in histological findings (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.74), age (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.23), or endometrial thickness (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.88). Power analysis revealed only 14% power to detect a 10% absolute difference in abnormal histology rates, and achieving 80% power would require 788 patients (394 per group).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this retrospective case series, no endometrial hyperplasia or cancer was identified among 24 women with documented HRT status. However, the study was severely underpowered to detect rare but clinically significant pathologies. The absence of abnormal findings likely reflects the small sample size and low baseline incidence, rather than a protective effect. The high rate of missing HRT documentation (61.3%) represents a significant quality gap. These findings underscore the limitations of small retrospective series and highlight the need for adequately powered, prospective studies with systematic HRT characterization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1718508","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:48:26Z","timestamp":1773384506000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Histological signatures of hormone replacement therapy in the endometrium"],"prefix":"10.3389","volume":"13","author":[{"given":"Mena","family":"Abdalla","sequence":"first","affiliation":[{"name":"Princess Royal University Hospital, King\u2019s College Hospital NHS Foundation Trust","place":["London, United Kingdom"]},{"name":"The Faculty of Medicine, Health & Life Sciences, Queens University Belfast","place":["Belfast, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.atherosclerosis.2016.10.005","article-title":"Back to the future: hormone replacement therapy as part of a prevention strategy for women at the onset of menopause","volume":"254","author":"Lobo","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.3390\/cancers12082195","article-title":"Menopausal hormone therapy and risk of endometrial cancer: a systematic review","volume":"12","author":"Tempfer","year":"2020","journal-title":"Cancers (Basel)"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.maturitas.2016.05.013","article-title":"Hormone replacement therapy and the risk of endometrial cancer: a systematic review","volume":"91","author":"Sj\u00f6gren","year":"2016","journal-title":"Maturitas"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1001\/jama.2017.11217","article-title":"Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the women\u2019s health initiative randomized trials","volume":"318","author":"Manson","year":"2017","journal-title":"JAMA"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"802959","DOI":"10.3389\/fmed.2021.802959","article-title":"Association between hormone replacement therapy and endometrial cancer risk: a systematic review and meta-analysis","volume":"8","author":"Liang","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1080\/13697137.2016.1187123","article-title":"The impact of micronized progesterone on the endometrium: a systematic review","volume":"19","author":"Stute","year":"2016","journal-title":"Climacteric"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1158\/1055-9965.EPI-20-1046","article-title":"Hormone replacement therapy, reproductive factors, and endometrial cancer risk: a prospective cohort study","volume":"30","author":"Dunneram","year":"2021","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1080\/13697130802050165","article-title":"Unscheduled bleeding in postmenopausal women taking hormone replacement therapy: a diagnostic approach","volume":"11","author":"Giannella","year":"2008","journal-title":"Climacteric"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00404-025-08161-w","article-title":"Endometrial thickness and pathology in postmenopausal women with bleeding on transdermal 17\u03b2-estradiol plus body-identical progesterone","volume":"313","author":"Glynne","year":"2025","journal-title":"Arch Gynecol Obstet"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1080\/13697137.2024.2412345","article-title":"Breast and endometrial safety of micronised progesterone in menopausal hormone therapy","volume":"27","author":"Lundell","year":"2024","journal-title":"Climacteric"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"k4810","DOI":"10.1136\/bmj.k4810","article-title":"Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases","volume":"364","author":"Vinogradova","year":"2019","journal-title":"BMJ"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1718508\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:48:27Z","timestamp":1773384507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1718508\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":11,"alternative-id":["10.3389\/fmed.2026.1718508"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1718508","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"article-number":"1718508"}}