Endocrine effects of the podophyllotoxine derivative drug CPH 82 (Reumacon(R)) in patients with rheumatoid arthritis

CPH 82 is a non-steroid antirheumatic drug containing two benzylidenated po dophyllotoxin glucosides with no affinity for the glucocorticoid receptor. Treatment with CPH 82 as single drug therapy significantly decreased serum and urinary cortisol and cortisol metabolites, serum adrenal androgens and urinary androgen metabolites, plasma ACTH and serum interleukin-6 (IL-6) an d tumor necrosis factor or (TNF-alpha), and increased serum levels of sex h ormone-binding globulin (SHBG). Significant positive correlations were foun d between serum TNF-alpha and plasma ACTH and between serum IL-6 and TNF-al pha on the one hand and serum and urinary cortisol and cortisol metabolites on the other. The initial action of CPH 82 on adrenal steroidogenesis may be a reduction in cytokine levels due to the drugs' antiinflammatory effect. This causes d ecreased ACTH stimulation, resulting in a reduced adrenocortical steroid se cretion. Accumulation of the drug in the adrenal cortex may also affect adr enal steroidogenesis. The elevated SHBG levels may be caused by a weak estr ogenic activity of the drug.