Androgen metabolism in gingival hyperplasia induced by nifedipine and cyclosporin

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Abstract
Three cases of gingival overgrowth induced by cyclosporin and/or nifedipine have been reported. Patient A was under medication with cyclosporin plus nifedipine, Patient B with nifedipine only and Patient C with cyclosporin only. The significance of androgen metabolism in gingival tissue, with respect to hyperplastic changes has been studied by several workers. Hence, we have investigated whether gingival tissue from the above patients showed significant metabolism of the androgen, testosterone, to its biologically-active form, 5α-dihydrotesto-sterone (5α-DHT). Radical gingivectomy was carried out in all 3 cases to remove the hyperplastic tissue. The excised tissue was incubated with labelled testosterone in order to study the extent of androgen metabolism. Healthy gingivae from males and females produced 5α-DHT (22.4 ± 7.7, s.e.m., n – 8). Very significantly higher values (p < 0.001) were recorded for Patients A, B and C (1139, 542 and 994 fmol/mg, respectively). These represented increases of 51-, 24- and 44.4-fold, respectively over control values. Corresponding production of 4-andro-stenedione from testosterone was 28±8.3, s.e.m., n = 8, fmol/mg. In Patients A, B and C, 4-androstenedione production was elevated: 85, 901 and 113 fmol/mg, respectively, representing increases of 3-, 32- and 4-fold. Even the lower values of 85 and 113 fmol/mg were very highly significant (p < 0.001) compared with control values. Although healthy female gingival tissue does not metabolize testosterone significantly, in the presence of inflammation the extent of 5α-DHT formation is comparable to that of male samples. For comparative purposes, the results of a previous study relating to phenytoin and androgen metabolism are included, since phenytoin is the third of the main drugs which cause the gingival overgrowth phenomenon. The relevant part of the study concerns the effects of phenytoin on a 180 g supernatant of fibroblasts derived from inflamed tissue. At a concentration of 10 μg/ml, phenytoin caused an approximately 160-fold increase in 5α-DHT formation from testosterone in the inflamed tissue fibroblast preparation compared with the non-inflamed preparation.