Male Gynecomastia

Abstract

A 62-year-old man with known coronary artery disease and ischemic left ventricular dysfunction presented with chest discomfort. His history was remarkable for New York Heart Association (NYHA) class IV congestive heart failure with depressed left ventricular ejection fraction. Physical examination revealed severe gynecomastia. The patient had been taking spironolactone (25 mg) daily for 8 years as part of his medication regimen for congestive heart failure. Spironolactone had been prescribed on the basis of RALES (Randomized Aldactone Evaluation Study), which reported spironolactone's benefits in reducing morbidity and mortality in patients with NYHA class III or IV heart failure.1Mosenkis A Townsend RR Gynecomastia and antihypertensive therapy.J Clin Hypertens (Greenwich). 2004; 6: 469-470PubMed Google Scholar Gynecomastia is a well-described adverse effect of spironolactone and is related to dose and duration of treatment; overall prevalence is 10%.1Mosenkis A Townsend RR Gynecomastia and antihypertensive therapy.J Clin Hypertens (Greenwich). 2004; 6: 469-470PubMed Google Scholar Spironolactone induces gynecomastia by decreasing testosterone production, increasing peripheral conversion of testosterone to estradiol, and displacing estradiol from sex hormone-binding globulin.1Mosenkis A Townsend RR Gynecomastia and antihypertensive therapy.J Clin Hypertens (Greenwich). 2004; 6: 469-470PubMed Google Scholar, 2Prisant LM Chin E Gynecomastia and hypertension.J Clin Hypertens (Greenwich). 2005; 7: 245-248Crossref PubMed Scopus (14) Google Scholar Generally, discontinuation of treatment results in resolution of gynecomastia. In 1999, RALES reported that spironolactone, in addition to standard therapy, decreases morbidity and death rates in patients with NYHA class III or IV heart failure. Gynecomastia or breast discomfort was reported as an adverse event in 10% of the men who participated in RALES.3Pitt B Zannad F Remme WJ Randomized Aldactone Evaluation Study Investigators et al.The effect of spironolactone on morbidity and mortality in patients with severe heart failure.N Engl J Med. 1999; 341: 709-717Crossref PubMed Scopus (7555) Google Scholar Other trials in which spironolactone was used have reported similar rates.4Chapman N Dobson J Wilson S Anglo-Scandinavian Cardiac Outcomes Trial Investigators et al.Effect of spironolactone on blood pressure in subjects with resistant hypertension.Hypertension. 2007; 49 (Epub 2007 Feb 19.): 839-845Crossref PubMed Scopus (513) Google Scholar Gynecomastia is defined as at least 2 cm of dense, subareolar tissue.2Prisant LM Chin E Gynecomastia and hypertension.J Clin Hypertens (Greenwich). 2005; 7: 245-248Crossref PubMed Scopus (14) Google Scholar It is seen in obese and elderly patients. Gynecomastia develops because of alterations in the ratio of free androgen to estrogen. Usual causes include enhanced peripheral aromatization of androgen to estrogen (obesity), displacement of estrogen from sex hormone-binding globulin, or decreased metabolism. Decreases in free androgen may occur as a result of increased sex hormone-binding globulin, increased metabolism, or impaired synthesis of androgen. Declining androgen synthesis is associated with the development of gynecomastia in elderly men. Gynecomastia can be an adverse effect of medications. Many antihypertensive medications have been associated with the development of gynecomastia, but it is highest with spironolactone.1Mosenkis A Townsend RR Gynecomastia and antihypertensive therapy.J Clin Hypertens (Greenwich). 2004; 6: 469-470PubMed Google Scholar Dosages higher than 150 mg/d have been associated with up to a 52% prevalence of the adverse effect. Generally, the effects are reversible after discontinuation of the drug. TABLEAntihypertensive Medications Associated With Gynecomastia Potassium-sparing diuretics SpironolactoneCalcium channel blockers NifedipineAmlodipineDiltiazemVerapamilAngiotensin-converting enzyme inhibitors CaptoprilEnalaprilα-Receptor blockers DoxazosinPrazosinCentrally acting agents ClonidineMethyldopaReserpine Open table in a new tab Spironolactone induces gynecomastia by blocking androgen production, by blocking androgens from binding to their receptors, and by increasing both total and free estrogen levels.1Mosenkis A Townsend RR Gynecomastia and antihypertensive therapy.J Clin Hypertens (Greenwich). 2004; 6: 469-470PubMed Google Scholar, 5Rose LI Underwood RH Newmark SR Kisch ES Williams GH Pathophysiology of spironolactone-induced gynecomastia.Ann Intern Med. 1977; 87: 398-403Crossref PubMed Scopus (156) Google Scholar Production of testosterone is decreased by inhibiting 17α-hydroxylase and 17,20-desmolase, which are enzymes in the testosterone synthesis pathway. Estrogen levels are increased by enhancing the peripheral conversion of testosterone to estradiol and by displacing estradiol from sex hormone-binding globulin. A selective aldosterone antagonist (eplerenone) has a lower incidence of gynecomastia, but the cost is higher.6Pitt B Remme W Zannad F Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators et al.Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction [published correction appears in N Engl J Med. 2003;348(22):2271].N Engl J Med. 2003; 348 (Epub 2003 Mar 31.): 1309-1321Crossref PubMed Scopus (4086) Google Scholar