Clinical Context

After menopause, the incidence of osteoarthritis (OA) increases, which may reflect accompanying hormonal changes. Estrogen deficiency appears to increase risk for OA, and there may be an association of hormone therapy (HRT)with the development of OA, in part through effects on the cartilage.

Knee OA is the most common type of OA, with treatment limited to symptom control using nonsteroidal anti-inflammatory drugs or arthroplasty, both of which may have adverse effects in the elderly. Whether there is any relationship between knee OA and HRT is still unclear. Using large-scale national data from the 2009 to 2012 Korea National Health and Nutrition Examination Survey, the investigators studied the association between knee OA prevalence and HRT among postmenopausal women.

Study Synopsis and Perspective

Postmenopausal women receiving HRT were significantly less likely to develop symptomatic knee OA compared with those who did not receive HRT, a nationwide cross-sectional observational study shows. But both the authors and an outside expert say the results should be viewed with caveats in mind.

"Participants receiving HRT had a significantly lower prevalence of symptomatic knee OA compared with those who did not receive HRT. However, this cross-sectional study precludes conclusions about causal relationships, so further prospective studies and intervention trials should be undertaken to establish a causal association between knee OA and HRT," the researchers write.

Jae Hyun Jung, MD, PhD, from Korea University College of Medicine, Inchon-ro, Seongbuk-gu, and the Division of Rheumatology, Department of Internal Medicine, Korea University Guro Hospital, Gurodong-ro, Guro-gu, both in Seoul, South Korea, and colleagues report their findings in an article published online December 21 in Menopause.

The researchers analyzed data from 4766 postmenopausal women who participated in the Korea National Health and Nutrition Examination Survey between 2009 and 2012. They defined HRT as receiving regular hormone medication for at least 1 year and defined knee OA according to symptoms and radiographic findings.

The 441 women in the HRT group were 30% less likely to have OA compared with the 4325 women in the non-HRT group (odds ratio, 0.70; 95% confidence interval, 0.50-0.99), after adjusting for HRT duration, age, obesity, age of menarche and menopause, hypertension, diabetes mellitus, alcohol intake, smoking status, and socioeconomic status.

"[T]he P value according to HRT showed statistical significance, but the 95% [confidence interval] was close to 1.00. This suggests that reproducibility problems may arise if other participants are included in this survey," the researchers explain. "However, the results were meaningful because the [Korea National Health and Nutrition Examination Survey] participants represent the entire Korean population with minimum selection bias."

Leonard Reeves, MD, a practicing family physician in Rome, Georgia, urges clinicians to exercise caution when interpreting these study results. "The [American Academy of Family Physicians] and [US Preventive Services Task Force (USPSTF)] recommend against hormone replacement therapy in postmenopausal women, as the harms of estrogen therapy outweigh the benefits. According to the USPSTF, although the use of hormone therapy to prevent chronic conditions in postmenopausal women is associated with some benefits, there are also well-documented harms," Dr Reeves told Medscape Medical News.

"This study was conducted in Korea, so the results may not translate to the US. There are many factors that differ between the 2 countries and populations. Additionally, the authors acknowledge that since the confidence interval approaches 1, the addition of more patients may diminish the observed effect. Therefore, it is important to not overestimate the impact of the study and carefully weigh the benefits and harms of treatment," Dr Reeves explained.

All general characteristics differed significantly between the HRT and non-HRT groups except hypertension, smoking status, and household income level. Age, body mass index, and the prevalence of diabetes "were significantly higher in the non-HRT group than in the HRT group," the authors write.

Education level was higher in the group that received HRT compared with the group that did not. The HRT group was younger at menarche and older at menopause compared with the non-HRT group.

"Past and current users of hormone therapy had a lower prevalence of knee joint osteoarthritis, suggesting that hormone therapy may be protective against knee [OA]," JoAnn Pinkerton, MD, North American Menopause Society executive director, said in a news release. "This study suggests that estrogen taken at menopause may inhibit cartilage damage and reduce knee deterioration seen on x-rays."

The authors and Dr Reeves have disclosed no relevant financial relationships.

Menopause. Published online ahead of print December 21, 2018.^[1]

Clinical Implications

• The prevalence of symptomatic knee OA was lower in postmenopausal women who received long-term HRT than in those who did not receive HRT, based on an analysis of large-scale Korean national data.
• The investigators suggest that supplementation with exogenous female hormones after menopause may protect against knee OA symptoms and radiographic changes, but further research is needed.
• Implications for the Healthcare Team: This study suggests that estrogen taken at menopause may inhibit cartilage damage and reduce knee deterioration seen on x-rays. There are differing position statements on the benefits and risks of HRT therapy in postmenopausal women. The American Academy of Family Physicians and USPSTF recommend against HRT in postmenopausal women because they believe the harms of estrogen therapy outweigh the benefits. The North American Menopause Society executive director supports use of HRT in OA as these study results showed benefit. Based on the evidence, healthcare providers should perform a risk-benefit analysis individualized for women who want to start hormonal therapy for prevention of knee osteoarthritis.

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