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Release: Feb. 8, 2000

Researchers want more studies for juvenile rheumatoid arthritis

IOWA CITY, Iowa -- A team of University of Iowa Health Care researchers believes the medical community should focus more on understanding how hormones affect juvenile rheumatoid arthritis (JRA) in an effort to determine whether hormone therapy might help alleviate the progression of the disease.

"We must conduct additional studies in the area of hormones as they relate to juvenile rheumatoid arthritis so that the medical community can finally come to a consensus on the issue," said Mary Hendrix, Ph.D., UI professor and head of anatomy and cell biology. "Only then can we begin to look at ways that hormones might be used to treat the often debilitating condition."

Zhila Ellis, Ph.D., a member of the Hendrix laboratory, outlines the Hendrix lab's plea for more investigations in an article appearing in the February issue of BioDrugs.

JRA is a chronic inflammatory disease in children, affecting mostly girls. The prevalence of JRA in females suggests that sex steroids may play a role in the condition. Like its adult counterpart, rheumatoid arthritis (RA), JRA is a progressive disease that erodes the articular cartilage, often leading to deformities and disabilities.

For more than 50 years, many researchers have believed that hormones play some part in RA, and numerous studies have been conducted. However, no one has ever really looked at hormones and their involvement in JRA.

Ellis and Hendrix suggested that previous studies in this area have been hampered by the lack of access to sufficient numbers of matched patient blood and tissue samples. Through valuable clinical collaboration with Terry Moore, M.D., director of JRA and RA clinics at St. Louis University, the UI was able to conduct a JRA/hormone investigation.

Hendrix's laboratory identified low levels of adrenal androgens in the serum and synovial fluid of patients with JRA. Synovial fluid is a lubricant in joints, and serum is the fluid portion of the blood.

The researchers examined the synovial fluid and serum from 21 patients with JRA -- half were between ages 5 and 12, the other half were between 15 and 18. Specifically, the researchers wanted to analyze the serum and synovial fluid for levels of testosterone, as well as the hormones dehydroepiandrosterone (DHEA) and its sulphated conjugate DHEA-S, progesterone and 17 beta-estradiol. The investigators then compared the hormone levels in the synovial fluid and serum to the

level found in the serum of a control group of subjects. The researchers did not look at the synovial fluid from the control group because it would be almost impossible to sample the small amount found in non-inflamed joints.

The UI data showed reduced levels of DHEA-S and testosterone in the synovial fluid and serum of patients with JRA. In addition, the ratio of DHEA/DHEA-S in both synovial fluid and serum was much higher than that of the corresponding control serum, thus indicating the potential importance of hormonal imbalances in the JRA disease process.

Although past investigations involving hormones used to treat RA have shown mixed results, which could be explained by variations in laboratory techniques and/or patient populations, some recent clinical trials of testosterone in both male and female patients with RA have proven more beneficial.

"Additional laboratory studies are urgently needed to better understand the precise role of hormones in arthritis so that better therapeutic interventions can be developed," Hendrix said.

University of Iowa Health Care describes the partnership between the UI College of Medicine and the UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide.