Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Sarrah L Hannon; Jennifer Andrews; Christina Laukaitis

doi:10.1016/j.jsbmb.2026.107090

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Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Sarrah L Hannon·Jennifer Andrews·Christina Laukaitis

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Abstract

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n = 45) and those with hEDS (n = 45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

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Humans Female Ehlers-Danlos Syndrome Adult Androgens Fibroblasts Middle Aged Skin Metabolomics Joint Instability Connective tissue Sex hormones Transcriptomics Journal Article

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Sarrah L Hannon, Jennifer Andrews, Christina Laukaitis. 2026-07-25. Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.. https://doi.org/10.1016/j.jsbmb.2026.107090

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