RESEARCH - Anti-TNF and sex hormones

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Ann N Y Acad Sci. 2006 Jun;1069:391-400.

Anti-TNF and sex hormones.

Research Laboratory and Division of Rheumatology, Department of Internal

Medicine-University of Genova, Viale Benedetto XV6, 16132, Genova, Italy.

mcutolo@...

Whenever serum estrogen concentrations are normal in rheumatoid arthritis

(RA) patients, lower androgen concentrations (i.e., testosterone,

androstenedione, and dehydroepiandrosterone sulfate [DHEAS]) are detected in

the serum as well as in the synovial fluid of male and female RA patients.

The presence in the RA synovial fluid of a significant altered sex hormone

balance resulting in lower immunosuppressive androgens and higher

immuno-enhancing estrogens, might determine a favorable condition for the

development of the immunomediated RA synovitis. The inflammatory cytokines

(i.e., TNF-alpha), particularly increased in RA synovitis, are able to

markedly stimulate the aromatase activity in peripheral tissues and,

therefore, induce the peripheral metabolism from androgens to estrogens. The

effects of TNF blockers (and generally of anticytokine agents) on peripheral

sex hormone levels seem exerted in a faster way at the level of the RA

synovial tissue (before any influence on serum levels) where they seem to

block the conversion from androgens (anti-inflammatory) to estrogens

(proinflammatory) induced by aromatase. Therefore, the beneficial effects of

restoring synovial androgens might be clinically more evident in male RA

patients (as recently observed in ANTARES study) since they suffer more for

the lack of androgens (anti-inflammatory) on account of the action of

TNF-alpha on peripheral hormonal conversion. However, therapy (3 months)

with anti-TNF did not change serum levels of typical sex hormones in

patients with RA, although baseline values were largely different from

controls. In patients with at least long-standing RA, this indicates that

alterations of serum sex hormones and altered activity of respective

converting enzymes are imprinted for a long-lasting period over at least 12

weeks.

PMID: 16855166

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=16855166

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