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

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


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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital / blood*
  • Adrenal Hyperplasia, Congenital / physiopathology*
  • Adult
  • Case-Control Studies
  • Electrocardiography*
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Gonadal Steroid Hormones / blood*
  • Gonadotropins / blood*
  • Heart Rate / physiology*
  • Humans
  • Luteinizing Hormone / blood
  • Male
  • Progesterone / blood
  • Testosterone / blood


  • Gonadal Steroid Hormones
  • Gonadotropins
  • Testosterone
  • Progesterone
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone