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Using RNA sequencing and MethylationEPIC array analyses, we compared myometrial tissue from women without fibroids (MyoN, n\u2009=\u200933), with fibroids (MyoF, n\u2009=\u200966), and after testosterone therapy as part of clinical care for gender dysphoria (MyoT, n\u2009=\u20097). The transcriptomic and methylation profiles of MyoT clustered with MyoF and were distinct from MyoN. We identified 1,321 differentially expressed protein-coding genes between MyoT and MyoN, while only 494 were found between MyoT and MyoF. Disease ontology analysis of MyoT vs. MyoN revealed enrichment of the fibroid tumor gene set. Fibroid associated genes including\n                    <jats:italic>TGF\u03b23<\/jats:italic>\n                    ,\n                    <jats:italic>CCND1<\/jats:italic>\n                    ,\n                    <jats:italic>SERPINE1,<\/jats:italic>\n                    and\n                    <jats:italic>FGFR1<\/jats:italic>\n                    were upregulated in MyoT and MyoF samples compared to MyoN samples. The DNA methylation profiles of MyoT were closer to those of MyoF, but no correlation was observed between methylation status and gene expression. Our preliminary data suggest that exogenous testosterone induces transcriptional and methylation changes in the myometrium consistent with those observed in MyoF tissues. These findings suggest that elevated testosterone may be associated with an increased risk of developing uterine fibroids.\n                  <\/jats:p>","DOI":"10.1007\/s43032-025-01893-9","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T11:11:19Z","timestamp":1749121879000},"page":"2223-2232","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Human Myometrial Transcriptome and the DNA Methylome of Testosterone-treated Patients Resemble the Myometria from Fibroid Patients"],"prefix":"10.1007","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5714-4994","authenticated-orcid":false,"given":"Emmanuel N.","family":"Paul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J.","family":"Carpenter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bossick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghassan","family":"Allo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesa R.","family":"Wegienka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"issue":"3","key":"1893_CR1","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1093\/molehr\/gat083","volume":"20","author":"SJ Holdsworth-Carson","year":"2014","unstructured":"Holdsworth-Carson SJ, et al. Clonality of smooth muscle and fibroblast cell populations isolated from human fibroid and myometrial tissues. Mol Hum Reprod. 2014;20(3):250\u20139.","journal-title":"Mol Hum Reprod"},{"issue":"1","key":"1893_CR2","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1067\/mob.2003.99","volume":"188","author":"DD Baird","year":"2003","unstructured":"Baird DD, et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188(1):100\u20137.","journal-title":"Am J Obstet Gynecol"},{"key":"1893_CR3","doi-asserted-by":"crossref","unstructured":"Baird, D.D., et al., Uterine fibroid incidence and growth in an ultrasound-based, prospective study of young African Americans. 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