title: Pharmacodynamics of a contraceptive vaginal ring releasing norethindrone and estradiol: ovarian function, bleeding control and lipoprotein patterns.
abstract: A new contraceptive vaginal ring (CVR), releasing approximately 700 micrograms of norethindrone (NET) and approximately 140 micrograms of estradiol (E2) daily, was studied in eleven women for a total of 61 21-day cycles. Ovarian function, as judged by plasma progesterone (P) and E2 levels, and plasma NET levels were studied by weekly blood samples in 30 cycles. The lipoprotein pattern was studied before, after two and six months of treatment and one month after completed treatment. The CVR gave rise to stable plasma NET levels which however varied considerably between individuals. Signs of luteal activity/ovulation were encountered in 4/30 cycles, all in subjects with the lowest NET plasma levels. E2 levels above 250 pmol/l, indicating follicular activity, were encountered in 22/30 cycles. Breakthrough bleeding and spotting appeared in 40/61 cycles and in 12 per cent of the treatment days. Bleeding control was significantly better in the same subjects when using a CVR releasing levo-Norgestrel and E2. Serum and HDL cholesterol concentrations decreased significantly by 10-12 per cent during treatment. The ratios between apolipoproteins A-I and A-II on one hand and HDL cholesterol on the other increased significantly and the ratio apolipoprotein A-I:A-II decreased significantly, indicating a change in the lipoprotein composition. These changes are qualitatively similar but quantitatively not as pronounced as with the more extensively studied 1-Ng/E2 CVR. The difference in clinical performance and in the effects on the lipoprotein pattern between the presently studied CVR and the 1-Ng/E2 CVR is most likely the result of not using equipment doses of gestagen in the CVRs.
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002986:Clinical Trials as Topic; D003270:Contraceptive Agents / Q000008:administration & dosage*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008598:Menstruation / Q000187:drug effects*; D009640:Norethindrone / Q000008:administration & dosage* / Q000097:blood; D009644:Norgestrel / Q000008:administration & dosage; D010060:Ovulation / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D003270:Contraceptive Agents; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D014280:Triglycerides; D009644:Norgestrel; D011374:Progesterone; D004958:Estradiol; D002784:Cholesterol; D009640:Norethindrone