title: Effect of two oral contraceptives with different ethinyl estradiol and levonorgestrel concentrations on the urinary excretion of biochemical vasoactive markers.
abstract: In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic peptide formed in the kidney, were measured as markers. In a comparative, double-blind, randomized, parallel group study, 34 women received Leios and 33 women Stediril 30. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged for both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, crucial for the resulting effect on vascular tone, increased significantly. For the serotonin metabolite, no changes were observed for both contraceptives. The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values. These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers, at least after 12 cycles of treatment. The positive influence of these contraceptives on the various markers investigated may improve vascular tone, impede development of atherosclerosis and arterial thrombosis, and improve water and electrolyte homeostasis. These effects most likely can be attributed to the estrogenic component. Levonorgestrel may elicit no impact on these estrogen-induced changes that, however, seem only to be manifested after a longer treatment period.
authors.affiliation: Section of Gynecological Endocrinology and Menopause, Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany. endo.meno@med.uni-tuebingen.de
authors.forename: A O
authors.initials: AO
authors.lastname: Mueck
authors.forename: H
authors.initials: H
authors.lastname: Seeger
authors.forename: G
authors.initials: G
authors.lastname: Petersen
authors.forename: E
authors.initials: E
authors.lastname: Schulte-Wintrop
authors.forename: D
authors.initials: D
authors.lastname: Wallwiener
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000652:urine*; D015415:Biomarkers; D002319:Cardiovascular System / Q000187:drug effects; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000494:pharmacology*; D006152:Cyclic GMP / Q000652:urine*; D004311:Double-Blind Method; D011464:Epoprostenol / Q000652:urine*; D004997:Ethinyl Estradiol / Q000652:urine; D019304:Ethinyl Estradiol-Norgestrel Combination / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D016912:Levonorgestrel / Q000652:urine; D010446:Peptide Fragments / Q000652:urine*; D012701:Serotonin / Q000652:urine*; D013931:Thromboxanes / Q000652:urine*; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D015415:Biomarkers; D003277:Contraceptives, Oral, Combined; D010446:Peptide Fragments; D013931:Thromboxanes; D012701:Serotonin; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; C056452:Ularitide; D019304:Ethinyl Estradiol-Norgestrel Combination; D009320:Atrial Natriuretic Factor; D011464:Epoprostenol; D006152:Cyclic GMP