title: Effects of combined oral contraceptives containing levonorgestrel or chlormadinone on the endothelium.
abstract: BACKGROUND
  Although the use of combined oral contraceptives (COCs) is associated with an increased risk of arterial and venous thromboembolic events, less is known about the impact of COCs on endothelial function. The present study evaluated the effects on the endothelium of healthy women of combinations of 30 mcg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA) and 30 mcg EE/150 mcg levonorgestrel (LNG).
  
  
  METHODS
  Sixty-four healthy women were evaluated, 21 using a nonhormonal contraceptive method (control) and 43 using COCs, randomized to EE 30 mcg /CMA 2 mg or to EE 30 mcg/LNG 150 mcg. Anthropometric parameters, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), ultrasound markers of endothelial function, flow-mediated dilation (FMD) of the brachial artery, intima-media thickness (IMT) and common carotid artery stiffness were measured at randomization and 6 months later.
  
  
  RESULTS
  Relative to baseline, EE/CMA users showed a significant reduction in mean DAP at 6 months (p=.02), and EE/LNG users showed a significant increase in mean IMT (p=.02) and a significant reduction in mean FMD (p=.01) at 6 months. DAP at 6 months was significantly lower in COC users than in controls (p=.01). Intergroup evaluations showed that, at 6 months, mean SAP (p=.02) was significantly lower in EE/LNG users than in controls (p=.02) and that mean DAP was significantly lower in EE/CMA (p<.01) and EE/LNG (p=.01) users than in controls. EE/LNG users experienced a mean FMD reduction almost threefold greater than that of EE/CMA users. Compared to controls, EE/LNG users experienced a 7.5-fold greater reduction in mean FMD.
  
  
  CONCLUSIONS
  COC containing LNG is associated with more pronounced changes in the FMD and IMT of healthy women than a COC containing CMA and nonhormonal contraception. Further studies are needed to determine whether these differences may lead to higher risk of arterial thromboembolic events.
authors.affiliation: Department of Gynecology and Obstetrics, Medical School of Ribeirão Preto, University of São Paulo, Brazil. Avenida Bandeirantes, 3900-Campus Universitário-Monte Alegre-Ribeirão Preto, SP, CEP-14049-900, Brazil.
authors.forename: Silvio Antonio
authors.initials: SA
authors.lastname: Franceschini
authors.forename: Carolina Sales
authors.initials: CS
authors.lastname: Vieira
authors.forename: Wellington P
authors.initials: WP
authors.lastname: Martins
authors.forename: Janaína Boldrini
authors.initials: JB
authors.lastname: França
authors.forename: Rui Alberto
authors.initials: RA
authors.lastname: Ferriani
mesh_terms: D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D001938:Brazil / Q000453:epidemiology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000187:drug effects; D059168:Carotid Intima-Media Thickness; D002715:Chlormadinone Acetate / Q000009:adverse effects*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects*; D004997:Ethinyl Estradiol / Q000009:adverse effects; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects*; D008137:Longitudinal Studies; D011372:Progestins / Q000009:adverse effects*; D012306:Risk; D013923:Thromboembolism / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D059289:Vascular Stiffness / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000009:adverse effects; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D011372:Progestins; D014662:Vasoconstrictor Agents; D002715:Chlormadinone Acetate; D004997:Ethinyl Estradiol; D016912:Levonorgestrel