Association of progesterone levels with pain intensity in postmenopausal women with knee osteoarthritis

Background Postmenopausal women are disproportionately affected by knee osteoarthritis (OA) and report greater pain severity compared to age-matched men. Although sex differences in OA pain are well recognized, the contribution of gonadal hormones to these differences remains poorly understood. Objectives This study examined the relationship between circulating gonadal hormone levels, pain intensity, and radiographic severity in patients with knee OA. Design We recruited 40 male and 34 female participants with radiographically confirmed knee OA. Demographic and clinical data were collected through self-reported questionnaires. Methods Venous blood was collected, and plasma concentrations of 17β-estradiol, estrone, progesterone, testosterone, and sex hormone–binding globulin were quantified using enzyme-linked immunosorbent assay. Results In the 49–60-year age range, female patients with knee OA reported significantly higher pain intensity than their male counterparts, while there was no difference in other age groups. Within this female subgroup, plasma progesterone levels positively correlated with pain intensity. Additionally, the plasma concentrations of progesterone, estrone, and testosterone were significantly lower in female subjects compared to male subjects. Moreover, the concentrations of plasma progesterone and SHBG were positively associated with the radiographic severity of knee OA in female participants, whereas 17β-estradiol levels showed a negative correlation with the radiographic score. No association between pain intensity and radiographic score was observed in either group. Conclusions These findings suggest that elevated progesterone levels, possibly reflecting hormonal instability during the perimenopausal–postmenopausal transition, may be associated with heightened pain susceptibility and greater structural disease severity in women with knee OA.