NEW YORK (Reuters Health) – Circulating levels of estradiol that are too high or too low are associated with increased mortality in men with chronic heart failure, according to a study appearing in the May 13th issue of the Journal of the American Medical Association.

Low androgen levels have been linked to morbidity and mortality in men with chronic heart failure, Dr. Ewa A. Jankowska, from Military Hospital, Wroclaw, Poland, and colleagues note in their report. Because estrogens come from androgen aromatization, it would be expected that estrogen metabolism is abnormal in these patients as well.

To investigate, the research team analyzed data from 501 men with chronic heart failure seen at two cardiology centers in Poland. The average ejection fraction was 28% and 52, 231, 181, and 37 men, respectively, had New York Heart Association (NYHA) class I, II, III, and IV heart failure. The subjects were divided into quintiles based on their serum estradiol level.

During 3 years of follow-up, 171 men (34%) died, the report indicates.

The investigators found that men in the lowest (<12.90 pg/mL) and highest (37.40 pg/mL or higher) estradiol quintiles were 4.17-times and 2.33-times more likely to die during follow-up than their peers in the middle quintile (21.80 to 30.11 pg/mL). Despite sharing an increased risk of death, the clinical characteristics of men in the lowest and highest estradiol quintiles were different. In the former, increased total testosterone, decreased DHEA-S, advanced NYHA class, impaired kidney function, and decreased total fat mass were noted, while in the latter, increased bilirubin and liver enzyme levels, as well as decreased sodium, were key clinical features. On multivariate analysis, the 3-year survival rates were 44.6%, 65.8%, 82.4%, 79.0%, and 63.6% for men going from the lowest to highest estradiol quintile. “Further studies,” the authors conclude, “are needed to explain the origin of these hormonal derangements.” At this point, they emphasize, it is premature to treat men with heart failure with agents that increase or decrease estradiol levels. Reference:
JAMA 2009;301:1892-1901.