Association of progesterone levels with pain intensity and synoviocyte activation in postmenopausal female subjects with knee osteoarthritis

ABSTRACT: Objective. Post-menopausal female subjects are overrepresented among people with knee osteoarthritis (OA) and report worse pain compared to male subjects of similar age and radiographic score. Our study investigated whether plasma levels of gonadal hormones are associated with pain intensity, radiographic scores, and an altered proteomic signature of the synovial tissue. Methods. Blood samples and synovial membrane tissues were collected from 40 male and 34 female subjects with OA. Patient information was gathered via self-reported questionnaires. Plasma concentrations of estradiol, estrone, progesterone, testosterone, and sex hormone-binding globulin were measured using ELISA. Sex-based differences in the activation of molecular pathways within the synovial membrane were assessed through proteomic analysis. Results. Female subjects with knee OA reported higher pain intensity than male subjects in the 49-60 years age window and in this group plasma progesterone positively correlated with pain intensity. Additionally, the concentration of plasma progesterone positively correlated with the radiographic score. The synovial tissue of female subjects with knee OA exhibited a distinct protein signature compared to male subjects, with an upregulation of proteins associated with the activation of the protein synthesis machinery and RNA metabolism, and a downregulation of proteins of the extracellular matrix organization (ECM), Fibroblast Growth Factor and the Receptor Tyrosine Kinase B signaling pathways. Furthermore, two distinct subject groups were identified based on plasma progesterone levels with low progesterone associated with increased cellular activity and reduced complement cascade and ECM organization pathways. Conclusion. This study suggests the importance of post-menopausal concentrations of progesterone in modulating OA-related pain and disease progression.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Synovial Cell, Synovial Tissue

DISEASE(S): Osteoarthritis

SUBMITTER: Evelin Berger  

LAB HEAD: Carina Sihlbom Wallem

PROVIDER: PXD061120 | Pride | 2026-10-07

REPOSITORIES: Pride