Menstrual Cycles Point to Link Between Sex Hormones and Long QT

SAN FRANCISCO -- Cardiac repolarization dynamics seemed to cycle in sync with the menstrual cycle of some people with congenital and drug-induced long QT syndrome (LQTS), a small prospective study showed.

Women with LQTS type 2 were found to have their QT interval -- corrected with the Bazett formula (QTcB) and Fridericia's method (QTcF) -- inversely correlate with progesterone levels and the progesterone/estradiol ratio. The RR interval correlated with estradiol, and T-wave duration with testosterone, according to Ilan Goldenberg, MD, of University of Rochester Medical Center in New York.

The link between sex hormones and QT appeared to be genotype-specific, as these findings were not observed in those with LQTS type and unaffected relatives, he said in a presentation at the Heart Rhythm Society (HRS) annual meeting.

Yet sex hormone levels did track with QT in a separate cohort of people taking QT-prolonging drugs.

It had been known that women with congenital LQTS are at greater risk for cardiac events after the onset of adolescence and during the postpartum and perimenopause periods.

Goldenberg suggested that sex hormones may modulate the cardiac potassium channels (e.g., the hERG channel associated with LQTS type 2 and drug-induced LQTS) and make people more prone to ventricular arrhythmias during certain phases of the menstrual cycle.

The investigator said that with a better understanding of the interplay between sex hormones and cardiac repolarization dynamics, it may be possible to factor hormones into risk stratification for arrhythmic events in LQTS and use hormone therapy for congenital and drug-induced LQTS.

HRS session discussant James Daubert, MD, of Duke University Medical Center in Durham, North Carolina, cited prior research that had suggested increased progesterone levels to be a risk for people with LQTS, which is the opposite finding of the present study.

Indeed, Goldenberg and colleagues previously reported that progestin-containing oral contraceptives were associated with a more than two-fold excess risk of cardiac events in women with LQTS -- a risk that appeared to be mitigated with beta-blockers.

Questions also remain regarding how the timing and day-to-day variability of sex hormones might relate to the risk of life-threatening events in an individual, as well as how complex the interaction is between ion channels and hormones and their ratios, according to Daubert.

"This is important work that will be important to patients, and more work is certainly needed regarding this," he stated.

The study comprised 105 women with regular menstrual cycles, and average age in the 30s, who were not taking exogenous sex hormones.

Participants included volunteers with congenital LQTS type 1 (n=24) or 2 (n=20) and their unaffected female relatives (n=21). Separately, there were also users of sotalol or dofetilide said to have drug-induced LQTS (n=20) and healthy controls (n=20).

All underwent 7-day ECG recordings that included the follicular phase, ovulation phase, and luteal phases of the menstrual cycle. The first day of each ECG recording cycle was accompanied by saliva testing for sex hormones.

Goldenberg said the findings have been accepted for publication in HeartRhythm.

Comment