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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

A comparison of the effects of danazol and gestrinone on testosterone binding to sex hormone binding globulin in vitro and in vivo.

Danazol and gestrinone are both effective agents in the treatment of endometriosis. Their mechanism of action is unknown but may be related to their androgenic activity, which is at least partly dependent on increases in the proportion of testosterone which circulates unbound to plasma protein. We have quantified these increases in patients on treatment, and by experimentation in vitro have demonstrated the relative importance of the reduction of sex hormone binding globulin (SHBG) binding capacity and competition with testosterone for SHBG binding sites by the drugs and some of their metabolites. The mean SHBG binding capacity in patients treated with danazol (400 mg/d, n = 7) and gestrinone (5 mg/week, n = 7) fell from 66.9 and 56.4 nmol/l to 36.1 and 28.1 nmol/l, after 1 week's treatment and to 11.1 and 7.1 nmol/l after 4 weeks respectively. Despite the similarity between the falls in SHBG binding capacity there was a significantly greater increase in % free testosterone in plasma samples from patients treated with danazol than in those from patients treated with gestrinone at 1 week. Experiments in vitro suggest that this was largely due to ethisterone (a major metabolite of danazol) competing with testosterone for SHBG binding sites. After 4 weeks on treatment there was a similar, near maximal reduction in SHBG binding of testosterone in both treatment groups. At the low levels of SHBG binding capacity reached by this time the extra effect of any competition for binding sites was much reduced.[1]

References

  1. A comparison of the effects of danazol and gestrinone on testosterone binding to sex hormone binding globulin in vitro and in vivo. Dowsett, M., Forbes, K.L., Rose, G.L., Mudge, J.E., Jeffcoate, S.L. Clin. Endocrinol. (Oxf) (1986) [Pubmed]
 
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