The medical treatment of endometriosis with danazol and gestrinone: A study of their clinical, endocrine and in vitro effects.

This thesis describes an investigation of the clinical efficacy and mechanisms of action of danazol and the newer steroidal agent, gestrinone in the medical management of endometriosis. A prospective randomized double-blind study was performed on 51 patients treated with either danazol or gestrinone. The efficacy and tolerance of the two drugs were shown to be similar. The endocrine effects of danazol and gestrinone were found to be analogous. Treatment with both drugs resulted in early follicular phase levels of luteinizing hormone, follicle stimulating hormone and oestradiol, a fall in sex hormone binding globulin and an increase in percent free testosterone and the concentration of free testosterone. The latter is significantly related to the improvement in endometriosis seen during treatment. Although vaginal bleeding and oestradiol levels during therapy are also significantly related, neither of these parameters correlate with effective elimination of endometriosis. The effect of gestrinone, danazol and the two major metabolites of danazol, ethisterone and 2-hydroxymethyl ethisterone were tested on endometrial tissue cells, used as a model for endometriotic tissue, cultured in vitro. In view of the increase in free testosterone observed during treatment with the drugs, the effect of testosterone was also examined. Danazol and testosterone at one and ten times the normal circulating concentrations caused a significant suppression of endometrial cell growth in vitro, but gestrinone, ethisterone and 2-hydroxymethyl ethisterone caused no effect.