The pain induced by degenerative knee osteoarthritis (KOA) is common in postmenopausal women, but there is a lack of clinical evidence on whether it has an association with decreased sex hormone levels and inflammatory cytokines in the synovial fluid.

To assess the associations of degenerative KOA pain with sex hormones in the serum 〔estradiol (E₂) , testosterone (T) , prolactin, luteinizing hormone (LH) , follicle-stimulating hormone (FSH) and progesterone (P) 〕, and inflammatory cytokines in synovial fluids 〔interleukin-1 (IL-1) , IL-6, IL-10 and tumor necrosis factor-α (TNF-α) 〕 in postmenopausal women, providing a novel basis for estrogen hormone treatment of pain induced by degenerative KOA.

Ninety postmenopausal women with pain induced by degenerative KOA were recruited from the Sixth Affiliated Hospital of Xinjiang Medical University from June 2019 to June 2021, including 30 with mild pain (VAS score ≤ 3) , 30 with moderate pain (VAS score higher than 4 but lower than 7) , and 30 with severe pain (VAS score higher than 7 but lower than 10) . They were compared to 30 postmenopausal women with knee effusion (controls) undergoing physical examination in the hospital during the same period. The levels of serum sex hormones and inflammatory cytokines in synovial fluids were measured in all cases. All subjects were tested for sex hormones in the serum and inflammatory cytokines in synovial fluids.

The BMI differed across mild, moderate, and severe pain subgroups and the controls (P<0.05) . In particular, severe pain subgroup had higher BMI than did controls and mild pain subgroup (P<0.05) . The serum levels of E₂ and T differed across mild, moderate, and severe pain subgroups and the controls (P<0.05) . Specifically, the controls had higher levels of E₂ and T than did moderate and severe pain subgroups (P<0.05) . The E₂ level in the moderate pain subgroup was lower than that of mild pain subgroup (P<0.05) . The E₂ and T levels in the severe pain subgroup were lower than those in the mild pain subgroup (P<0.05) . There were no significant differences in prolactin, LH, FSH and P between controls, and mild, moderate and severe pain subgroups (P>0.05) . The levels of IL-1, IL-6, and IL-10 as well as TNF-α varied across mild, moderate, and severe pain subgroups and the controls (P<0.05) . Compared with controls, mild pain subgroup had higher IL-1 level, and moderate and severe pain subgroups had higher IL-1, IL-6, IL-10 and TNF-α levels (P<0.05) . The levels of IL-6, IL-10 and TNF-α in severe pain subgroup were higher than those in mild pain subgroup (P<0.05) . E₂ and T levels were negatively correlated with VAS score for degenerative knee pain (r_s=-0.686, -0.454, P<0.05) ; IL-1, IL-6 and TNF-α levels were positively correlated with VAS score for degenerative knee pain (r_s=0.517, 0.665, 0.319, P<0.05) . There was no correlation between IL-10 and VAS score for degenerative knee pain (r_s=0.162, P>0.05) .

In postmenopausal women, VAS score for degenerative knee pain was negatively correlated with E₂ and T levels. There was no significant difference in prolactin, LH, FSH and P levels among degenerative KOA patients with different pain levels. The IL-1, IL-6 and TNF-α levels in synovial fluids were positively correlated with the VAS score of degenerative knee pain. So reducing the levels of IL-1, IL-6 and TNF-α could improve the tolerance of knee pain, which may be a reference for clinical treatment of degenerative knee pain.