Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis

Objective: To investigate the longitudinal association between endogenous sex hormones and knee osteoarthritis (OA) structures and pain.

Method: We examined 200 participants (mean age 63.0 ± 7.3 years) from a clinical trial of vitamin D supplement for symptomatic knee OA. Serum levels of estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) were analyzed at baseline and 24 months later. Magnetic resonance imaging (MRI) scans of selected knee were obtained at both baseline and follow-up for the measurement of cartilage volume, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis volume. Knee pain was assessed using a 100 mm visual analogue scale (VAS). Longitudinal data were analyzed using linear mixed-effects model.

Results: One hundred and seven males and 93 females were included in this study. For females, after adjustment for age, body mass index (BMI), and vitamin D level, progesterone was positively associated with cartilage volume (β = 0.12 mm³ per quartile, P < 0.01). Estradiol levels were associated with lower grades of BMLs (β = -0.46 per quartile, P = 0.03), while estradiol (β = -1.28 per quartile, P = 0.04), progesterone (β = -1.56 per quartile, P < 0.01) and testosterone (β = -1.51 per quartile, P = 0.01) were inversely associated with effusion-synovitis volume. Testosterone was inversely associated with knee pain. No consistent associations were observed for males.

Conclusion: In women but not men, low serum levels of endogenous estradiol, progesterone and testosterone are associated with increased knee effusion-synovitis and possibly other OA-related structural changes. This may contribute to observed sex differences in knee OA.