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Endocrine Derangements and Heart Failure

List of key references prepared and regularly updated by the Heart Failure Association (HFA)



Acute postischemic treatment with estrogen receptor-alpha agonist or estrogen receptor-beta agonist improves myocardial recovery

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Vornehm ND, Wang M, Abarbanell A, Herrmann J, Weil B, Tan J, Wang Y, Kelly M, Meldrum DR.

Surgery 2009;146(2):145-54.

Synopsis

In an experimental model of isolated perfused hearts (Langendorff) from male rats, the postischaemic infusion of the selective estrogen receptor (ER)-alpha agonist and the selective ER-beta agonist significantly improved myocardial function, increased myocardial vascular endothelial growth factor, and there was a trend towards lower lactate dehydrogenase in myocardium as compared to hearts exposed only to perfusate.

Commentary

Estrogens have been shown to protect female heart, but evidence on their beneficial effects on male myocardium is scarce.  The study provides experimental evidence that the stimulation estradiol signaling pathways through both alpha and beta specific receptors reveals protective effects during the ischaemia/reperfusion injury also in male subjects.  There is a need to establish the mechanisms of cardioprotective effects of estrogens, as this may be useful for the development of novel therapeutic strategies to be applied in both men and women. 

Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction

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Nanda A, Chen MH, Braccioforte MH, Moran BJ, D'Amico AV.

JAMA 2009;302(8):866-73.

Synopsis

The authors studied 5077 men (median age, 69.5 years) with localized or locally advanced prostate cancer, where some of them received 4-month hormonal (antiandrogenic) therapy. During a median follow-up of 5 years, a pharmacological depletion of androgen activity affected the outcome among neither men with no co-morbidities nor those with a single cardiovascular risk factor (diabetes mellitus, hypercholesterolemia, or hypertension).  However, antiandrogenic therapy increased all-cause mortality in men with known coronary artery disease resulting in heart failure or myocardial infarction.

Commentary

Deficiencies in androgens (testosterone and dehydroepiandrosterone) have been demonstrated to be predictors of unfavourable outcome in men with systolic chronic heart failure in previous observational studies.  In this paper, a pharmacological induction of androgen deficiency resulted in an increased risk of death in men with previous myocardial infarction and/or ischaemic chronic heart failure, which was along with the previous results.  It is suggested that normal androgen metabolism is particularly important for patients with injured myocardium.  The presented results provide crucial information for both cardiologists and oncologists, demonstrating the detrimental effects of commonly used anti-androgen therapy.

Circulating estradiol and mortality in men with systolic chronic heart failure

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Jankowska EA, FESC, Rozentryt P, Ponikowska B, Hartmann O, Kustrzycka-Kratochwil D, Reczuch K, Nowak J, Borodulin-Nadzieja L, Polonski L, Banasiak W, Poole-Wilson PA, Anker SD, Ponikowski P, FESC.

JAMA. 2009 May 13;301(18):1892-901.

Synopsis

The study demonstrates that there is a U-shaped relationship between serum estradiol level and 3-year mortality in men with systolic chronic heart failure (CHF), irrespectively of circulating androgen levels and clinical prognosticators.  Interestingly, men with low and high circulating estradiol had different clinical characteristics.  These with low serum estradiol had increased serum total testosterone, decreased serum dehydroepiandrosterone sulphate, advanced NYHA class, impaired renal function, and decreased total fat tissue mass.  There with high serum estradiol had increased serum bilirubin and liver enzymes, and decreased serum sodium.

Commentary

Estrogens have generally been considered as female hormones.  Recently there is increasing evidence that estrogens play a crucial role in the physiology and pathophysiology of cardiovascular system also in males.  In fact, the aromatization of testosterone to estradiol is not just a way of degradation, but the product of this reaction has several important biological properties.  According to published analyses, both low and high estradiol levels are linked to increased mortality in men with systolic chronic heart failure.  The origin of these derangements of estradiol metabolism as well the precise mechanisms responsible for U-shaped relation between circulating estradiol and mortality in examined patients are unknown.  It may be hypothesized that a modulation of metabolism of androgens and estrogens might bring favourable effects in male patients with chronic heart failure.  Further studies are needed to precisely established the beneficial/detrimental mechanisms.