ANN ARBOR, Mich.—Low concentrations of estradiol and urinary 2-hydroxyestrone may increase the risk of developing knee osteoarthritis among women approaching menopause, according to new research in the August issue of Arthritis & Rheumatism.1


The recent study showed that women with the lowest levels of circulating estradiol were nearly twice as likely to develop osteoarthritis (OA) of the knee over a 3-year period as women with higher levels of the hormone, and those with the lowest levels of 2-hydroxyesterone were at nearly three times the risk.

"This research may open doors in terms of prevention and treatment."   —MaryFran Sowers, PhD
"This is really important because there is a great need to understand the processes associated with the development of OA, and this research may open doors in terms of prevention and treatment," lead author Mary Fran R. Sowers, PhD, professor of epidemiology at the University of Michigan in Ann Arbor, told CIAOMed.

In the first effort to look at naturally occurring estrogen profiles, researchers examined estradiol and two of its metabolites (2-hydroxyestrone and 16 -hydroxyestrone) to determine if their levels are associated with an increased risk of developing OA in 842 premenopausal or perimenopausal women from the Southeast Michigan Arthritis Cohort. Participants underwent annual radiographs of both knees along with analysis of of estradiol and its metabolites. They were also interviewed regarding pain, health, and lifestyle. All subjects were followed for 3 years.

Women in the lowest tertile of estradiol level (less than 47 pg/mL) were significantly more likely to have developed OA of the knee than those in the middle tertile (47 to 77 pg/mL), after the researchers adjusted for age, injury, and body mass index. The women with the lowest levels of 2-hydroxyesterone were at increased risk for developing OA, and those with the highest ratio of 16α-hydroxyesterone to 2-hydroxyesterone were also at higher risk, the study showed.

Although the underlying mechanism is not fully understood, Dr. Sowers suspects that the increased OA risk reflects the modulation that occurs in the prostaglandin synthesis pathway, with corresponding effects on Cox-1 and Cox-2 products.


"We are a long way from treatment and prevention strategies, [as] this is the first time people have looked at naturally occurring estrogen profiles," Dr. Sowers cautioned. "Most of the work has been done with hormone replacement therapy."

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Reference

1. Sowers MFR, McConnell D, Jannausch M, et al. Estradiol and its metabolites and their association with knee osteoarthritis. Arthritis Rheum. 2006;54:2481-2487.