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-deso gestrel has been determined during several clinical studies with diffe rent oral contraceptive formulations and one in vitro study. The resul ts of these studies were combined in order to assess the relation betw een 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 SH BG. Although marked differences in protein binding were seen for the t hree progestins at low concentrations of SHBG, these differences becam e less pronounced at high levels of SHBG which were reached during est ablished oral contraceptive therapy. A nonlinear relation could be sho wn for either the free or the protein-bound fraction of the progestins and the concentration of SHBG in the serum, respectively.