Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis.
To investigate the longitudinal association between endogenous sex hormones and knee osteoarthritis (OA) structures and pain.



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.



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 mm3per 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.



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.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Jin
Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Victoria, Australia.
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Wang
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Wang
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Antony
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Zhu
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Han
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Cicuttini
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Wluka
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
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Winzenberg
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Blizzard
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Jones
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Arthritis Research Institute, 1st Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address: Changhai.Ding@utas.edu.au.
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Ding
D000368:Aged; D018771:Arthralgia / Q000209:etiology / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D002357:Cartilage Diseases / Q000209:etiology / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D002762:Cholecalciferol / Q000008:administration & dosage; D004334:Drug Administration Schedule; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D013585:Synovitis / Q000209:etiology / Q000473:pathology
D050071:Bone Density Conservation Agents; D012739:Gonadal Steroid Hormones; D002762:Cholecalciferol
Bone marrow lesion; Cartilage; Effusion synovitis; Osteoarthritis; Sex hormone