Androgenizing effects of cyclosporin A in rheumatoid arthritis

In order to determine the influence of CsA on whole peripheral androgen metabolism, we evaluated 14 patients with RA over a period of 12 months. Patients were treated with low-dose CsA (2.5-3.5 mg/kg/day). Other drugs influencing androgen metabolism were excluded. Plasma levels of Test and of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (Adiol-G), an important peripheral Test metabolite, were analyzed. Each patient was monthly examined for the first three months, and thereafter every three months. At each visit, the number of swollen and tender joints, as well as the visual analogic scale of pain, were evaluated. The laboratory parameters of RA activity (ESR, CRP, Hb) were also monitored, along with some safety serological indexes. Statistical analysis was performed by using nonparametrical tests. After 12 months of treatment, an evident increase in mean plasma Adiol-G concentration was observed in patients of both sexes (women's basal levels +/- SE = 2.89 +/- 0.58 ng/mL vs. 12 months = 5.71 +/- 1.33 ng/mL; men's basal levels = 4.87 +/- 0.91 vs. 9.20 +/- 0.68, respectively) (p < 0.001). The increase was already statistically significant after 4-5 weeks of treatment in male patients (p < 0.01) and after 12-14 weeks in female patients (p < 0.05). All the patients experienced the side effect of a low-degree hypertrichosis after a mean period of 4-8 weeks. Concerning clinical parameters, a significant improvement (p < 0.05) of the number of swollen and tender joints was observed after 12 months, as well as a reduction of CRP levels. No statistically significant correlation between hormonal levels and clinical or laboratory indexes of disease activity was observed. In conclusion, the appearance of a dose-related hypertrichosis and the increase in plasma androgen metabolites (Adiol-G) in CsA-treated patients should be regarded as possible markers of the influence of CsA on peripheral androgen metabolism, at the level of target cells and tissues.