GROUP COMPARISON OF SERUM ETHINYL ESTRADIOL, SHBG AND CBG LEVELS IN 83 WOMEN USING 2 LOW-DOSE COMBINATION ORAL-CONTRACEPTIVES FOR 3 MONTHS

Serum ethinyl estradiol (EE2), sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were studied in healthy young women randomly allocated to one of two low-dose combination oral contraceptives containing 30-mu-g EE2 and either 75-mu-g gestodene (F) or 150-mu-g desogestrel (M) per unit. There was either no (formerly non-pill users) or one (pill users) wash-out cycle before the study started with a pill-free pretreatment cycle in which the hormone status and basal SHBG and CBG levels were measured. Treatment was for three months. During treatment cycles 1 and 3, there were three test days each. Seven serum samples were obtained up to four hours and one sample 24 hours after intake of the first, tenth and the last (21st) pill. Additional samples were taken prior to morning ingestion of pills 5 and 15. For each individual and each test day, a representative serum pool has been constructed for SHBG and CBG analysis. EE2 concentrations were analyzed in all individual samples by means of a specific and sensitive RIA using anti-EE2-6-beta-CMO-BSA antiserum. Area under the curves (AUC) up to 4 and 24 hours, C(max) and t(max) were evaluated and compared between the two treatment groups (n = 40 for F, n = 43 for M). SHBG and CBG concentrations were measured using commercially available immunoassay kits. Groups were large enough to detect a difference in group means of 75 % of one standard deviation (alpha = 0.05, 1-beta = 0.9) of target variables, which is equivalent to 28 pg EE2/ml for C(max), 69 pg.h.ml-1 for AUC(EE)2 0-4h, 257 pg.h.ml-1 for AUC(EE)2 0-24h, 39 nmol/1 SHBG and 13.4-mu-g CBG/ml. Results clearly demonstrate that there were no differences between the two treatment groups in any of the target variables at any of the six test days distributed over a three-month period. Mean SHBG and CBG pretreatment levels of about 70 nmol/l and 37 mu-g/ml, respectively, increased to about 210 nmol/l and 88 mu-g/ml during the first treatment cycle and to about 230 nmol/l and 93 mu-g/ml during the third treatment cycle. Whereas the time of maximum EE2 serum levels did not differ significantly between test days, C(max) AUC(EE2) 0-4h and AUC(EE2) 0-24h values increased by 30-35% or 40-50%, respectively, when test days 10 and 21 were compared to test day 1. Similar results were found for the third treatment cycle. From the results of the present study, it can be concluded that the pharmacokinetic characteristics of EE2 were not different between the OCs investigated. Concomitantly administered progestins, gestodene and desogestrel, did not influence differently EE2 systemic availability and its serum level profile. The two preparations were equally effective in inducing SHBG and CBG levels.