Very low dose danazol in idiopathic thrombocytopenic purpura and its role as an immune modulator.

Danazol, an attenuated androgen, has been used successfully at its conventional dose (400-800 mg/day) in the treatment of idiopathic thrombocytopenic purpura (ITP). To minimize side effects, the authors tried a very low dose (50 mg/day) regimen which has not been used in any other disease and observed its efficacy in ITP. Fifteen patients were given this dosage of danazol. Its effects on T-cell subsets, B cells, and blastogenic response to pokeweed mitogen (PWM) and staphylococcus aureus (Staph A) were studied before and during therapy. The percentage of CD3 and the percentage and numbers of CD4 were significantly increased during therapy. Responses to PWM, a T-cell dependent B cell mitogen, were also significantly elevated during therapy. However, no change in the percentage of B (CD19) lymphocytes and response to Staph A, a polyclonal B cell mitogen, were noted. There were seven excellent-good and eight fair-poor responses in platelet counts. The excellent-good responders were found to have a more stable CD4 subset between before and during therapy compared to the fair-poor responders (p less than 0.05, Fisher's exact test). Very low dose danazol regimen, therefore, produced a significant increase in the CD4 without affecting the B cells. However, the excellent-good responder patients showed no significant increase in the CD4 lymphocytes.

Inflammatory reaction in endometriotic tissue: an immunohistochemical study.

A panel of monoclonal antibodies specific for macrophage subtypes appearing in early (27E10), down-regulatory (RM3/1) and late (25F9) stages of inflammation had been applied to 20 endometriotic implants of 14 women. Of those patients 9 were in the follicular phase of the cycle, two on danazol, one on LHRH-analogue (buserelin) and another two on oral contraceptives. Beside the macrophage subsets, antibodies against T4, T8 lymphocytes as well as proliferating cells (EN7/44 and Ki67) were examined. In all specimens immunologically competent cells could be detected to a varying degree and within the same implant different stages of inflammation were discernible. Endometriosis presented with signs of early inflammation indicated by 27E10+ macrophages and CD4+ lymphocytes (15 specimens) and with down-regulatory, late inflammatory reactions as shown by RM3/1+, 25F9+ macrophages and CD8+ lymphocytes (19 biopsies). Additionally, in 14 specimens cells of the EN7/44+ and Ki67+ type was detected. These preliminary results showed no significant correlation to either extension of endometriotic implants or adhesions or concomitant therapy and clearly indicate, that there is an immunological dynamic process within the lesion itself in addition to that one of the peritoneal fluid.

Interference of danazol with the radioimmunoassay of steroid hormones.

The crossreactivity of Danazol, a synthetic steroidal drug with antigonadotropic and impeded androgenic properties, with 12 different antisera against 8 different steroids was studied either by conventional competitive inhibition assay or by competitive saturation assay, the latter of which was found to be more sensitive. It was shown that Danazol strongly reacted with an antiserum against 5 alpha-dihydrotestosterone and also, albeit to a much lesser extent, with antisera against testosterone, cortisol and progesterone in decreasing order. It did not interfere with RIA-systems for 11-desoxycortisol, 17 alpha-hydroxyprogesterone, estradiol-17 beta and estriol. However, out of four antisera against estradiol-17 beta two were found to considerably crossreact with Danazol which might explain apparent increases in plasma levels of this hormone during Danazol treatment as recently reported.

Danazol and its principal metabolites interfere with binding of testosterone, cortisol, and thyroxin by plasma proteins.

Danazol and its three principal metabolites (2-hydroxy-methylethisterone, 2-hydroxymethyl-1,2-dehydroethisterone, and ethisterone) competitively displace cortisol and testosterone from plasma proteins. This effect is in addition to the reported inhibition of the production of testosterone-binding globulin and thyroxin-binding globulin. We saw no competitive inhibition of thyroxin binding. Concentrations of total testosterone, total cortisol, and total thyroxin were low, whereas percentages of free testosterone, free cortisol, and free thyroxin were abnormally high in women being treated with danazol. Values for testosterone, cortisol, and thyroxin in danazol-treated patients should therefore be appropriately corrected before interpretation. Protein-binding assays for testosterone or cortisol that involve testosterone- or cortisol-binding globulin may be invalid in danazol-treated subjects because of the competitive binding of danazol and its metabolites to these proteins.