Influence of changes in the concentration of sex hormone-binding globulin in human serum on the protein binding of the contraceptive steroids levonorgestrel, 3-keto-desogestrel and gestodene.

The serum protein binding of levonorgestrel, gestodene and 3-keto-desogestrel has been determined during several clinical studies with different oral contraceptive formulations and one in vitro study. The results of these studies were combined in order to assess the relation between changes in the concentration of sex hormone-binding globulin (SHBG) and the effect on the free fraction of the progestins as well as on their distribution with respect to the binding proteins albumin and SHBG. Although marked differences in protein binding were seen for the three progestins at low concentrations of SHBG, these differences became less pronounced at high levels of SHBG which were reached during established oral contraceptive therapy. A nonlinear relation could be shown for either the free or the protein-bound fraction of the progestins and the concentration of SHBG in the serum, respectively.