ABSTRACT
OBJECTIVE: To compare the effects of oral and transdermal contraceptives containing similar hormone formulations on vascular risk markers. METHODS: We conducted a randomized, investigator-blinded, crossover, clinical trial with 24 healthy women, aged 18-35 years, who received 2 months of transdermal or oral contraceptive, 2 months washout, then 2 months of the alternative medication. The transdermal contraceptive contained 0.75 mg ethinyl estradiol and 6 mg norelgestromin. The oral contraceptive contained 35 mcg ethinyl estradiol and 250 mcg norgestimate. Blood samples taken before and after each treatment were analyzed in batch for D-dimer, von Willebrand factor, factor VIII, total and free protein S, antithrombin, fibrinogen, C-reactive protein, and normalized activated protein C sensitivity ratio (nAPCsr) determined with two thrombin generation-based assays, the alpha2macroglobulin-thrombin end point method (alpha2M-IIa) and calibrated automated thrombinography. Repeated measures analysis of variance was used for analysis. RESULTS: For both contraceptives (transdermal, oral) there were significant declines in free (19%, 11%) and total protein S (19%, 13%) and antithrombin (13%, 10%); increases in fibrinogen (8%, 10%), C-reactive protein (220%, 292%), nAPCsr alpha2M-IIa (81%, 61%), and nAPCsr calibrated automated thrombinography (102%, 68%), all P<.05. Transdermal contraceptives had a greater effect than oral contraceptives on free protein S (P=.07), nAPCsr alpha2M-IIa (P=.06), and nAPCsr calibrated automated thrombinography (P=.03). CONCLUSION: Oral and transdermal contraception with similar hormones had similar adverse effects on vascular risk markers. This suggests that this transdermal contraceptive has at least a similar thrombosis risk as its oral counterpart. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00554632 LEVEL OF EVIDENCE: I.
Subject(s)
Blood Coagulation/drug effects , Contraceptives, Oral, Hormonal/administration & dosage , Contraceptives, Oral, Hormonal/adverse effects , Thrombosis/chemically induced , Administration, Cutaneous , Adolescent , Adult , Analysis of Variance , Antithrombins/analysis , Antithrombins/metabolism , Blood Proteins/analysis , Blood Proteins/metabolism , C-Reactive Protein , Cross-Over Studies , Drug Combinations , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/adverse effects , Factor VIII/analysis , Factor VIII/metabolism , Female , Fibrinogen/analysis , Fibrinogen/metabolism , Humans , Norgestrel/administration & dosage , Norgestrel/adverse effects , Norgestrel/analogs & derivatives , Oximes/administration & dosage , Oximes/adverse effects , Protein S/analysis , Protein S/metabolism , Risk Factors , Thrombosis/blood , Thrombosis/epidemiology , von Willebrand Factor/analysis , von Willebrand Factor/metabolismABSTRACT
BACKGROUND: The ex utero intrapartum treatment (EXIT) procedure is a technique designed to establish an airway at the time of delivery in fetuses at risk of airway obstruction and requires maintenance of uterine relaxation to continue placental perfusion and prevent placental separation. We describe the use of intravenous nitroglycerin to maintain uterine relaxation during the EXIT procedure. CASE: A 17-year-old primigravida with a fetus known to have an anterior neck mass was admitted for a scheduled operative delivery at 38 weeks of gestation using a modified EXIT procedure. Anesthesia was administered with a combined spinal-epidural technique. Intravenous nitroglycerin was administered as a bolus and then as a continuous infusion to maintain uterine relaxation until evaluation of the neonatal airway was completed. CONCLUSION: Intravenous nitroglycerin is an effective agent for maintenance of uterine relaxation and placental perfusion during the EXIT procedure.