Imbalance of Synovial Estrogen, Androgen Fuels Inflammation in RA

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Imbalance of Synovial Estrogen, Androgen Fuels Inflammation in Rheumatoid

Arthritis

By Rauscher

NEW YORK (Reuters Health) Jan 15 - In patients with rheumatoid arthritis

(RA), local synovial fluid (SF) levels of proproliferative and

proinflammatory estrogens are elevated relative to anti-inflammatory

androgens, according to a new study. Determining the molar ratio of SF

estrogens to SF androgens " may be a helpful diagnostic tool for the

assessment of the local inflammatory situation, " say the researchers.

" The observed shift in the direction of estrogens in relation to androgens

is a supporter of the inflammatory process in arthritis, " lead author Dr.

Rainer H. Straub from University Medical Center in Regensburg, Germany, told

Reuters Health.

In the study, the overall concentration of free estrogens in SF tended to be

higher in the 12 subjects with RA than in the 8 subjects with traumatic knee

injury (noninflammatory controls), but the finding was not statistically

significant. The ratio of free SF estrogens to free SF androgens was also

elevated in RA subjects compared to control subjects (p = 0.017).

The results are published in the December issue of The Journal of

Rheumatology.

The investigators suspect that the " imbalance is most probably due to

increased aromatase activity, " noting that the free SF concentration of the

precursor androstenedione and SF estrone - the aromatase conversion product

of androstenedione - were also increased in RA subjects compared with

control subjects (p = 0.011 and p = 0.035, respectively).

The team also found that the sex steroid precursor dehydroepiandrosterone

(DHEA) is rapidly converted to estrogens in cultured synoviocytes.

The evidence from this study " may provide a basis to develop an alternative

hormonal therapy for RA patients, using strategies designed to achieve a

reduction in estrogen formation [with] aromatase inhibitors, " the

researchers conclude.

" Further, the parallel use of an aromatase inhibitor together with DHEA may

be much more anti-inflammatory, " they add.

J Rheumatol 2003;30:2597-2605.