ROTTERDAM, The Netherlands—Osteoarthritis (OA) incidence spikes in women over 50, but the widely-assumed link to menopausal hormone changes turns out to be a myth.

”The assumed relationship between the studied female hormonal aspects and OA of the hand, hip or knee was not clearly observed in this systematic review.”—Bianca de Klerk, MSc
Dutch researchers led by Bianca de Klerk, MSc, report early online in Rheumatology that a systematic review found no “clearly observed” associations between OA and female hormonal status.1

“The assumed relationship between the studied female hormonal aspects and OA of the hand, hip or knee was not clearly observed in this systematic review. Most evidence points in the direction of no relation between OA of the hand, hip and knee and the studied determinants remain conflicting,” de Klerk wrote.

Meta-analysis of female hip, knee, wrist OA

The incidence of osteoarthritis rises steeply in women over age 50, which suggested a link between OA and hormonal changes. To explore this possibility, de Klerk, of the Erasmus Medical Center at University Medical Center in Rotterdam, The Netherlands, searched Medline and EMBASE for articles that assessed associations between hand/hip/knee OA and female hormonal aspects.

“We wanted to make a high risk profile for the GP to use in his or her practice to help recognize people at high risk for OA development,” de Klerk told Musculoskeletal Report. The meta-analysis included 16 studies that dealt with hand, hip, or knee OA and some aspect of female hormonal status.

Specifically, de Klerk and her team looked at OA and aspects of the fertile period such as duration and age at menarche, as well as aspects of the menopausal period, such as age at menopause, years since menopause, and surgical menopause. They also assessed the methodological quality of the studies based on sample size, inclusion of the joints of interest, inclusion of female hormone changing events, and a focus on female hormones and an association with OA.

This analysis revealed:
  • conflicting evidence of an association between age at menarche and radiographic osteoarthritis (ROA)
  • conflicting evidence regarding age at menarche and incidence of Herberden’s nodes (HNs)
  • conflicting evidence regarding years since menopause and knee OA, and
  • conflicting evidence on whether there is a relationship between ovariectomy and hip OA.

The analysis did identify limited evidence of increased risk of incident radiologic knee OA associated with low estriadol serum levels in the early follicular phase. They also found increased likeliness of total hip replacement in women who had age at menarche of less than 11 years.

There was a limited protective effect for menopause greater than 52 years of age and total knee replacement.

Researchers surprised at lack of menopause effect in OA

The results were surprising to the research team.

“Since OA incidence rises in women around the age of 50 years, which has been known for a long time now, it is widely-assumed that the cause for the rise in this incidence has to be sought in an association with menopause,” de Klerk notes.

The intertwined nature of the determinants reviewed made it difficult to draw clear conclusions about the relationship between hormonal changes and OA. The researchers interpreted all non-significant outcomes as evidence of no relationship but admitted that study designs and/or sample sizes might have obscured an association.

de Klerk said, “We did not find such a clear association, but do not exclude the possibility of the existence of one. It is possible that such an association exists, but is just too complex to appear in observational studies.” Still, the preponderance of no association and weak association outcomes in their review led them to conclude that there is no clear relationship between the studied aspects and OA of the hand, hip and knee.

Translating research into practice: Menopause and OA

Reflecting on the implications of the findings, de Klerk said, “Since OA incidence rises in women around the age of 50 years, which has been known for a long time now, it is widely-assumed that the cause for the rise in this incidence has to be sought in an association with menopause. The clinical value of our work is that the physician cannot rely on the assessment of menopausal aspects for identifying women at high risk of OA development. Still, more research is needed.”

Reference

1. de Klerk BM, Schiphof D, Groeneveld FPMJ, et al. No clear association between female hormonal aspects and osteoarthritis of the hand, kip and knee: a systematic review. Rheumatology. 2009;[epub ahead of print] doi:10.1093/rheumatology/kep194.