Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis

Background: Hypoandrogenicity is common in obesity and in chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis ( RA). Adrenal androgens such as androstenedione (ASD) and dehydroepiandrosterone ( DHEA) sulphate are low, which partly depends on the influence of TNF in chronic inflammatory diseases. Leptin is stimulated by TNF and is associated with hypoandrogenicity in non-inflammatory conditions. Objective: To study the interrelation between serum levels of leptin and adrenal steroids in SLE and RA. Methods: In a retrospective study, serum levels of leptin, ASD, DHEA, and 17-hydroxyprogesterone (17OHP) were measured by ELISA, and serum levels of cortisol by radioimmunoassay in 30 patients with RA, 32 with SLE, and 54 healthy control subjects (HS). Results: In SLE and RA but not HS, serum levels of ASD correlated negatively with serum levels of leptin (p<0.01) independently of prior prednisolone treatment in patients with SLE (p=0.013) and tended to be independent of prednisolone in patients with RA (p=0.067). In a partial correlation analysis, this interrelation remained significant after controlling for daily prednisolone dose in both patient groups. In both patient groups, serum leptin levels correlated negatively with the molar ratio of serum ASD/serum cortisol and serum ASD/serum 17OHP, and positively with the molar ratio of serum DHEA/serum ASD. Conclusions: The negative correlation of serum leptin and ASD or, particularly, ASD/17OHP, together with its known anti-androgenic effects indicate that leptin is also involved in hypoandrogenicity in patients with SLE and RA. Leptin may be an important link between chronic inflammation and the hypoandrogenic state.