doi: 10.1161/CIRCULATIONAHA.106.685040
(Circulation. 2007;115:e548.)
© 2007 American Heart Association, Inc.
Correspondence |
Letter by Pascual-Figal et al Regarding Article, "Anabolic Deficiency in Men With Chronic Heart Failure: Prevalence and Detrimental Impact on Survival"
Departments of Cardiology and Biochemistry, University Hospital Virgen de la Arrixaca, Murcia, Spain
We read with interest the article by Jankowska et al,1 who show that anabolic hormone deficiency is common in heart failure (HF) patients. The article does not mention the proportion of patients treated with spironolactone, a steroid chemically related to the mineralocorticoid aldosterone, which acts as an antiandrogen that competes with dihydrotestosterone at the androgen-receptor level. Spironolactone also increases metabolic clearance and inhibits androgen production.2–4 This drug has long been used in the treatment of hyperandrogenism (primarily hirsutism, polycystic ovary syndrome, and familial male precocious puberty) in doses ranging between 50 and 400 mg/d, and it is associated with decreased levels of anabolic hormones.2–4
Additionally, the authors found that anabolic deficiency correlated inversely with New York Heart Association classification.1 Spironolactone at low doses (25–50 mg/d) is used in HF patients with New York Heart Association class III or IV and is associated with a better survival rate in this population.5 In this population, at least 10% of HF patients have sex hormone–related adverse effects (gynecomastia, breast pain, and impotence).5 Therefore, it is necessary to clarify whether the reported anabolic deficiency was a consequence of spironolactone use in HF patients.
Moreover, the authors show that a deficiency of each anabolic hormone is an independent marker of poor prognosis.1 Clinical benefits of spironolactone are attributed to the blockage of aldosterone production through a competitive blockade of the mineralocorticoid receptor. After reading the article by Jankowska et al, another question arises: Are the benefits of spironolactone dependent on anabolic status, or could they be blunted by its antiandrogenic actions? This question has not been previously studied, and no data exist. Relative to this point, eplerenone is a newer aldosterone antagonist that is much more selective than spironolactone, with minimal affinity for progesterone and androgenic receptors. The lack of antiandrogenic effects of eplerenone could confer an advantage not only in terms of fewer side effects but, more importantly, in terms of clinical benefit. The absence of direct comparisons between eplerenone and spironolactone makes this possibility an attractive hypothesis in severe HF.
All these issues raise a preliminary question about the interaction between spironolactone and anabolic hormones: Is spironolactone a "spectator" or a "real player" in the anabolic deficiency of HF syndrome? Further investigation will be necessary.
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Acknowledgments |
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Disclosures
None.
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References |
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 Top References |
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1. Jankowska EA, Biel B, Majda J, Szklrska A, Lopuszanska M, Medras M, Anker SD, Banasiak W, Poole-Wilson PA, Ponikowski P. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006; 114: 1829–1837.
2. Corvol P, Michaud A, Menard J, Friefeld M, Mahoudean J. Antiandrogenic effect of spironolactone: mechanism of action. Endocrinology. 1975: 97; 52–54.
3. McMullen GR, Van Herle AJ. Hirsutism and the effectiveness of spironolactone in its management. J Endocrinol Invest. 1993; 16: 925–932.[Medline] [Order article via Infotrieve]
4. Khurana ML, Eunice M, Gupta N, Gulati M, Dwivedi SN, Ammini AC, Ganie MA. Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. J Clin Endocrinol Metab. 2004; 89: 2756–2762.
5. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341: 709–717.
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