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As in people with VEDS, aortic risk in this model accelerates at the onset of puberty, especially in males. We identify developmentally regulated gene programs associated with this vulnerability and that are targeted by treatments that mitigate aortic risk. Both genetic and pharmacological inhibition of the androgen receptor (AR) eliminated survival differences between sexes, while treatment with a dual AR and mineralocorticoid receptor (MR) antagonist provided near-complete and durable protection in both sexes. Pathways targeted by dual AR\/MR inhibition, including those related to extracellular matrix (ECM) organization and cell-ECM interactions, largely overlapped with those also modulated by isolated MR antagonism. Selective targeting of MR signaling emerged as an effective therapeutic strategy in both sexes that avoids sexual side effects in males.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.198202","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:01:17Z","timestamp":1777392077000},"source":"Crossref","is-referenced-by-count":0,"title":["Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome"],"prefix":"10.1172","volume":"11","author":[{"given":"Emily E.","family":"Juzwiak","sequence":"first","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland USA."},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin J.","family":"Bowen","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins 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