SERUM CONCENTRATIONS OF ETHINYLESTRADIOL, 3-KETO-DESOGESTREL, SHBG, CBG AND GONADOTROPINS DURING TREATMENT WITH A BIPHASIC ORAL-CONTRACEPTIVE CONTAINING DESOGESTREL

During a cross-over study, the pharmacokinetics of ethinylestradiol (E E) and 3-keto-desogestrel (KDG) were investigated on days 7 and 22 of one cycle of treatment with two biphasic formulations containing 50 mu g EE (7 tablets) and 50 mug EE + 125 mug desogestrel (DG) (15 tablets) (50/50 EE) or 40 mug EE + 25 mug DG (7 tablets) and 30 mug EE + 125 m ug DG (15 tablets) (40/30 EE). Peak serum levels and areas under the c urve of EE increased significantly by 50% between days 7 and 22 of tho se taking 50/50 EE, while during treatment with 40/30 EE, no differenc e was found between days 7 and 22. Both formulations caused identical KDG levels on day 22. There were only slight differences in the effect s of both preparations on sex-hormone-binding globulin (SHBG; +150 to +160%) and on corticosteroid-binding globulin (CBG; +130 to +150%) on day 7. On day 22, the changes were more pronounced with 50/50 EE (SHBG , +310%; CBG, +240%) than with 40/30 EE (SHBG, +250%; CBG, +180%). On day 22 after discontinuation of treatment, the SHBG and CBG levels wer e still significantly above the control values. Using both formulation s, LH and FSH levels were significantly suppressed on day 22, while on day 7 no significant reduction was observed. The rise in the EE level s between days 7 and 22 of 50/50 EE intake and the time course of the EE concentrations during treatment with 40/30 EE appear to be due to a n inhibition of hepatic metabolism by the contraceptive steroids, as E E is nearly exclusively bound to albumin which does not change.