Female hormones influence knee replacement risk, but it’s complicated

Pregnancy and hormone use appear to be linked to an increased risk of knee replacements for osteoarthritis but the relationship is complex, Australian researchers say.

Conversely, a prolonged reproductive life decreased the risk of knee replacement for women of normal weight, reported the research team that included rheumatologists Anita Wluka and Flavia Cicuttini from the School of Public Health and Preventive Medicine at Monash University in Melbourne .

“[Our findings] add to the ongoing literature regarding the complex relationship of reproductive and hormonal factors and OA risk,” they wrote in their paper published in Arthritis and Rheumatology.

The study involving 22,289 women taking part in the Melbourne Collaborative Cohort study identified 1,208 total knee replacements (TKA) over a period of 12.7 years.

An increased risk of TKA with pregnancy and parity was seen in normal weight women but not in women who were overweight or obese. For example, ever pregnancy was associated with an increased TKA risk (HR=1.32) and parity was positively associated with TKA risk (p for trend=0.003).

“These findings suggest that the relationship between pregnancy, parity and TKA for OA is complex and may not simply be mediated through increased weight gain associated with pregnancy and parity,” the researchers  wrote.

Women who used oral contraceptives had an increased risk of TKA compared to non-users  (OCP<5 years, HR=1.25; OCP≥5 years, HR=1.17).

Age at menarche and menopause was not associated with TKA risk, but the number of years of menstruation was linked to a decreased risk of knee replacement but only for women of normal weight.

One year increase in menstruation was associated with 1% decreased TKA risk (HR=0.99, 95%CI 0.97‐0.99). These associations remained significant only in normal weight women at early reproductive age.

Current HRT users had increased TKA risk compared to non‐users (HR=1.33) but again, this association was significant only in non‐obese women at midlife.

The researchers speculated that a lack of association seen in overweight and obese women may be explained by the fact that they had already been exposed to increased mechanical loading, inflammation and endothelial dysfunction.

“This may mask any additional association between reproductive factors and TKA… if a person is obese, the excessive joint loading may be more likely to drive the OA pathogenesis and progression”.

Given the huge burden of knee OA and associated TKA in women worldwide, more research was needed to understand the complex association between reproductive factors and knee OA risk, and the role of obesity, they concluded.

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