Reproductive, Hormonal Factors Affect Risk for Total Knee Arthroplasty in Women

contraceptive pills
contraceptive pills
Researchers sought to identify associations of female reproductive factors with incidence of total knee arthroplasty in osteoarthritis.

History of pregnancy, increasing number of pregnancies, oral contraceptive use, current hormone replacement therapy use, and increasing duration of hormone replacement therapy are risk factors for total knee arthroplasty (TKA) resulting from osteoarthritis (OA), while prolonged years of menstruation decrease this risk, according to the results of a study published in Arthritis & Rheumatology.

Researchers from Monash University and Alfred Hospital in Melbourne, Australia, included 22,289 women from the Melbourne Collaborative Cohort Study in the investigation. They collected data regarding age at menarche, pregnancy, parity, years of menstruation, oral contraceptive pill use, menopausal status, and hormone replacement use between 1990 and 1994. They determined the incidence of TKA between 2001 and 2013 by linking cohort records with the National Joint Replacement Registry and adjusted all analyses for age, body mass index (BMI) at midlife, change in BMI from early reproductive age to midlife, country of birth, physical activity, smoking status, and education.

The investigators identified 1208 TKAs for osteoarthritis between 2001 and 2013. History of pregnancy was associated with increased TKA risk (hazard ratio [HR], 1.32; 95% CI, 1.06-1.63) and parity was also positively associated with TKA risk (P for trend =.003). Compared with nonusers, oral contraceptive users had an increased TKA risk (HR for oral contraceptive use <5 years, 1.25; HR for oral contraceptive use ≥5 years, 1.17). In contrast, a 1-year increase in menstruation was associated with a 1% decreased TKA risk (HR, 0.99; 95% CI, 0.97-0.99). However, these associations remained significant only in normal-weight women at early reproductive age. Women currently using hormone replacement therapy had an increased TKA risk over nonusers (HR, 1.33; 95% CI, 1.11-1.60), but this was only significant in women who were not obese at midlife.

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The authors suggest that the link between pregnancy and parity with increased risk for TKA may be the result of weight gain and retention. Greater body weight increases mechanical loading as well as inflammation and endothelial dysfunction caused by excessive fat mass, which are known to be risk factors for knee OA. However, the relationship between oral contraceptive use, hormone replacement therapy, and knee OA is complex and the authors call for further investigation.


Hussain SM, Wang Y, Giles GG, Graves S, Wluka AE, Cicuttini FM. Female reproductive and hormonal factors and incidence of primary total knee arthroplasty due to osteoarthritis [published online March 7, 2018]. Arthritis Rheumatol. doi: 10.1002/art.40483