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Reproductive, hormonal factors linked to knee OA risk in women
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Reproductive and hormonal factors, such as pregnancy, increasing number of offspring and hormone replacement therapy use, are associated with increased knee osteoarthritis risk, according to findings published in Arthritis and Rheumatology.
The researchers further concluded that the link remains significant among normal-weight women at early reproductive age as well as those who are nonobese at midlife.
“Obesity is the most important modifiable risk factors for knee OA,” Yuanyuan Wang, PhD, MMed, MBBS, of Monash University, Melbourne, Australia, told Healio Rheumatology. “A number of reproductive and hormonal factors, such as menarche, parity, menopause, use of oral contraceptive pill and hormone replacement therapy, are associated with obesity. As obesity may influence the hormonal status, it is important to examine whether the associations between reproductive and hormonal factors and knee OA differ based on obesity status. Our study is the first study investigating these associations based on women’s obesity status.”
To evaluate the associations between reproductive and hormonal factors among women undergoing total knee arthroplasty (TKA) for OA, and whether they vary by weight, the researchers examined data from the Melbourne Collaborative Cohort Study, which includes 41,514 participants recruited through electoral roll, advertisements and local media announcements from 1990 to 1994. Hussain and colleagues reviewed information on 22,289 women, including menarche, pregnancy, parity, years of menstruation, oral contraceptive pill use, menopausal status and hormone replacement therapy use.
The researchers determined TKA incidence from 2001 to 2012 by linking participant records to the National Joint Replacement Registry. Analyses were adjusted for age, BMI at midlife, change in BMI from early reproductive age to midlife, country of birth, physical activity, smoking and education.
According to the researchers, there were 1,208 TKAs for OA during the course of 12.7 years. Having been pregnant (HR = 1.32; 95% CI, 1.06-1.63), parity (P = .003) and oral contraceptive pill use (less than 5 years: HR = 1.25; 95% CI, 1.08-1.45; 5 or more years: HR = 1.17; 95% CI, 1-1.37) were associated with an increased risk for TKA. A 1-year increase in menstruation was associated with 1% decreased risk for TKA (HR = 0.99; 95% CI, 0.97-0.99). The above associations remained significant only in normal weight women at early reproductive age, the researchers wrote. Current hormone replacement use use was linked to an increased risk for TKA risk, compared with nonusers (HR = 1.33; 95% CI, 1.11-1.60); but only in nonobese women at midlife.
“These findings suggest that normal weight and overweight or obese women may be susceptible to different risk factors of knee OA,” Wang said in an interview. “It may be that in normal weight women reproductive and hormonal factors, by increasing body weight, inflammation and endothelial dysfunction, augment osteoarthritis development and progression, whereas overweight/obese women are already exposed to these risk factors for knee osteoarthritis which may mask any association between reproductive and hormonal factors and knee osteoarthritis.”
Wang added that if a person is overweight or obese, the excessive joint loading exerted by body weight might drive OA pathogenesis and progression.
“Women with normal weight at early reproductive age and women who are nonobese at midlife, if having the above-mentioned reproductive and hormonal exposure, would be at higher risk of development and/or progression of knee OA and thus should be targeted for the prevention and early intervention for knee OA,” she said. “Our findings add to the literature for the complex relationship of reproductive and hormonal factors with knee osteoarthritis, and the role of obesity in this relationship.” – by Jason Laday
Disclosure: The researchers report funding from the Australian National Health and Medical Research Council.
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