title: Complex Influence of Gonadotropins and Sex Steroid Hormones on QT Interval Duration.
abstract: QT interval duration is longer in women than in men. Sex steroid hormones have inconsistently been suggested to explain this difference. The implication of gonadotropins has never been studied.
  
  
  
  We report here the combined influence of sex steroid hormones and gonadotropins on QT interval duration in healthy subjects and patients with congenital adrenal hyperplasia (CAH) as a model of T and progesterone overexpression.
  
  
  
  Eighty-four CAH patients (58 women) and 84 healthy subjects matched and paired for sex and age were prospectively included. Circulating concentrations of 17-OH-progesterone, progesterone, T, estradiol, FSH, and LH were measured concomitantly to the recording of a digitized electrocardiogram.
  
  
  
  QTcFridericia (QTcF) was shorter in women with CAH than in control women (404 ± 2 vs 413 ± 2.1 milliseconds; P ≤ .001). 17-OH-progesterone, progesterone, the progesterone/estradiol ratio, and total T were higher in women with CAH than in female controls (P < .05), whereas FSH was lower (P ≤ .05). According to multivariable analysis in all women, the progesterone/estradiol ratio (β = -0.33) and FSH levels (β = 0.34) were related to QTcF (r = 0.5; P < .0001), with no influence of CAH or healthy status. QTcF was not different between CAH (404.7 ± 3.7 milliseconds) or healthy men (396 ± 2.8 milliseconds). For men, QTcF (r = 0.48; P < .01) was negatively related to free T (β = -0.29) and positively to FSH levels (β = 0.34).
  
  
  
  Cardiac repolarization is influenced by complex interactions between sex steroid hormones and gonadotropins, depending on gender. Our results indicate that the progesterone/estradiol ratio in women, T in men, and FSH in both genders are major determinants of ventricular repolarization with opposite effects on QTc interval.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Abehsira
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Anne
authors.initials: A
authors.lastname: Bachelot
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Fabio
authors.initials: F
authors.lastname: Badilini
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Laurence
authors.initials: L
authors.lastname: Koehl
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Martine
authors.initials: M
authors.lastname: Lebot
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Clement
authors.initials: C
authors.lastname: Favet
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Philippe
authors.initials: P
authors.lastname: Touraine
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Christian
authors.initials: C
authors.lastname: Funck-Brentano
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1421, F-75013 Paris, France; Inserm (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), CIC-1421 and Unité Mixte de Recherche (UMR), Institute of Cardiometabolism and Nutrition (ICAN) 1166, Sorbonne Universités, F-75013 Paris, France; l'université Pierre et Marie Curie (Paris 06) (G.A., L.K., M.L., C.F., C.F.-B., J.-E.S.), Pitié-Salpêtrière Hospital, IE3M, Department of Endocrinology and Reproductive Medecine, and Centre de Référence des Maladies Endocriniennes Rares de la croissance et Centre des Pathologies gynécologiques Rares, and CIC-1421, F-75013 Paris, France; AP-HP (A.B., P.T.), Pitié-Salpêtrière Hospital (J.-E.S.), Department of Cardiology-Rhythmology Unit, F-75013 Paris, France; and AMPS, LLC (F.B.), New York, New York 10025.
authors.forename: Joe-Elie
authors.initials: JE
authors.lastname: Salem
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000503:physiopathology*; D000328:Adult; D016022:Case-Control Studies; D004562:Electrocardiography; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006062:Gonadotropins / Q000097:blood*; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011374:Progesterone / Q000097:blood; D013739:Testosterone / Q000097:blood
chemical_list: D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone