Men with systolic chronic heart failure who have low or high levels of estradiol, a form of the hormone estrogen, have an increased risk of death compared with men with moderate levels of this hormone, according to a study in the May 13 issue of JAMA.

Estrogens have numerous biological effects in men and have a complex effect on the normal cardiovascular system, including cardioprotective effects, which may explain the link between low estradiol concentrations and an increased risk of cardiovascular events in men, according to background information in the article.

Ewa A. Jankowska, M.D., Ph.D., of the Center for Heart Disease, Military Hospital, Wroclaw, Poland, and colleagues examined the relationship between estradiol concentrations in the blood and the rate of death in men with chronic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The study, conducted at two cardiology centers in Poland, included 501 men (average age, 58 years). The patients were divided into 5 groups (quintiles), determined by the level of estradiol in their blood. Quintile 3 was considered the reference group.

Among the patients, 171 deaths (34 percent) occurred during the 3-year follow-up. Analysis indicated that the most favorable outcome was in patients with estradiol levels within the middle quintile, whereas the highest 3-year mortality rates were observed in men in the lowest quintile (about 4 times higher risk of death) and those in the highest quintile (about twice the risk of death) of circulating estradiol levels.

For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens (male sex hormones) were: 44.6 percent for quintile 1; 65.8 percent for quintile 2; 82.4 percent for quintile 3; 79.0 percent for quintile 4; and 63.6 percent for quintile 5.

"Both low and high concentrations of circulating estradiol are significant predictors of a poor prognosis, independently of gonadal and adrenal androgen deficiencies and conventional clinical prognostic indicators," the authors write. "Further studies are needed to explain the origin of these hormonal derangements."