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J Clin Endocrinol Metab. 2016 Jul;101(7):2776-84. doi: 10.1210/jc.2016-1877. Epub 2016 May 11.

Complex Influence of Gonadotropins and Sex Steroid Hormones on QT Interval Duration.

Author information

1
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.

Abstract

CONTEXT:

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.

OBJECTIVE:

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.

DESIGN AND PATIENTS:

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.

RESULTS:

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).

CONCLUSION:

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.

PMID:
27167057
DOI:
10.1210/jc.2016-1877
[Indexed for MEDLINE]

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