Higher parity, early menarche, oral contraceptive use affect TKR risk in women
Greater parity, early age at menarche, or oral contraceptive use may increase a woman’s risk of undergoing total knee replacement (TKR) for severe knee osteoarthritis (OA), according to findings from the Singapore Chinese Health Study (SCHS).
Of the 35,298 female SCHS participants of Chinese ethnicity who were aged 45–74 years, 1,645 underwent TKR due to severe knee OA over the mean 14.8-year follow-up period.
Interviews were conducted with all participants to determine lifestyle, parity, reproductive history, and comorbidities. Women who had undergone TKR were older at recruitment, had a higher BMI, a lower level of education, were less likely to be current smokers or have diabetes, and more likely to have hypertension compared with the rest of the women in the cohort.
Women who had more children had an elevated risk of undergoing TKR with the risk rising with increasing parity compared with nulliparous women (hazard ratio [HR], 1.21, 95 percent confidence interval [CI], 0.84–1.73 for one child, HR, 1.39, 95 percent CI, 1.03–1.88 for two children, HR, 1.91, 95 percent CI, 1.43–2.56 for three children, and HR, 1.99, 95 percent CI, 1.48–2.68 for four children), and the highest risk among women with ≥5 children (HR, 2.01, 95 percent CI, 1.50–2.70; ptrend<0.001). [Osteoarthritis Cartilage 2019;doi:10.1016/j.joca.2019.03.002]
BMI appeared to modify the higher parity-TKR risk, with a stronger risk demonstrated among underweight or normal weight women (BMI <23 kg/m2; HR, 4.86 [women with ≥5 children vs nulliparous women]) compared with overweight or obese women (BMI ≥23 kg/m2; HR, 1.57; pinteraction=0.001).
Age at menarche also affected TKR risk with women with early menarche having the highest risk compared with those who were aged ≥17 years at menarche (HR, 1.38 [age <13 years], HR, 1.37 [age 13–14 years], and HR, 1.19 [age 15–16 years]; ptrend<0.001).
Oral contraceptive use was also linked to elevated TKR risk (HR, 1.18, 95 percent CI, 1.05–1.32 for ever vs never users), with a stronger risk among those with 1–2 or ≥3 years of use (HR, 1.21 and 1.22, respectively; ptrend=0.002).
Conversely, age at menopause or use of hormone replacement therapy (HRT) in postmenopausal women did not appear to affect TKR risk, though the relatively low proportion of HRT users (6.6 percent) may have affected the results.
Research showing higher rates and greater severity of knee OA among women, especially after menopause, compared with men, has led to the suggestion of a potential role of hormonal factors in OA pathogenesis. [Osteoarthritis Cartilage 2005;3:769-781]
Some studies have shown a reduction in total knee cartilage volume with increasing parity, [Osteoarthritis Cartilage 2011;19:1307-1313] while others have pointed to an increase in serum oestradiol levels which correlated with an increase in ligament laxity during the third trimester of pregnancy. [Clin Orthop Relat Res 2001:165e70]
“Laxity of ligaments and soft tissue structures around the joints may explain the biological plausibility for the association between parity and development of severe knee OA,” said study lead author Associate Professor Katy Leung Ying Ying from the Singapore General Hospital and co-authors. “We also postulate that leaner women may be more susceptible to the detrimental stress that the increase in weight bearing and kinetic changes in gait during pregnancy may impose on the knee joints,” they said, calling for further research into establishing these findings.
The link between early age at menarche and TKR risk suggests that earlier or longer duration of exposure to “cyclic hormonal changes” could affect knee OA, they added, as could the elevated BMI that has been associated with early menarche. [Int J Obes (Lond) 2013;37:1036-1043]
However, due to the unavailability of information on previous history or other risk factors for knee OA, the authors were unable to ascertain if the associative factors applied to onset or progression of knee OA.