Canrenone and Androgen Receptor-Active Materials in Plasma of Cirrhotic Patients during Long-Term K-Canrenoate or Spironolactone Therapy

Andriulli, Angelo; Arrigoni, Arrigo; Gindro, T.; Karbowiak, I.; Buzzetti, Giampiero; Armanini, Decio

doi:10.1159/000199905

Cited by 12 publications

(4 citation statements)

References 13 publications

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“…Thus, spironolactone may act as a competitive inhibitor of androgen action. Indeed, it is used to reduce sexual hair growth in hirsute women with and without the polycystic ovary syndrome [ 117 ]. However, Stripp et al [ 97 ] report that there is no plausible mechanism to explain spironolactone induced gynecomastia, as the drug has been shown to cause changes only in progesterone and 17-hydroxyprogesterone values.…”

Section: Resultsmentioning

confidence: 99%

Gynecomastia and drugs: a critical evaluation of the literature

Nuttall

Warrier

Gannon

2015

Eur J Clin Pharmacol

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PurposeA large number of medications have been implicated in the genesis of gynecomastia. However, gynecomastia is common in men, asymptomatic, increases with age, and is considered to be due to an increased estradiol/testosterone ratio. This complicates the interpretation of medication-related gynecomastia. Therefore, we have reviewed the literature in order to assess the data relating gynecomastia onset with utilization of specific medications.MethodsThe literature was searched in PubMed and the Ovid/Medline databases from the 1946 to January 2015 with the search terminology of “gynecomastia, drugs/medications.” A few other articles were found and included.ResultsOne hundred ten publications were reviewed. Sixty-three were single case reports. There were 24 population-based studies of which 8 were HIV-infected patients treated with antiretroviral agents. Among the case reports, 49 were for individual medications, and 2 were reports of antineoplastic or antiretroviral drug regimens. In the great majority, mastodynia with or without breast enlargement was present and referred to as gynecomastia. Generally, hormonal profiles could not explain the breast enlargement. The pain/tenderness and breast enlargement resolved spontaneously over time.ConclusionMany different medications have been associated with the presence of “gynecomastia.” Generally, it presents as a syndrome characterized by a single painful/tender breast (mastodynia) associated with breast enlargement and is transient. We suggest that these cases be referred to as an acute gynecomastia syndrome. This syndrome also occurs independent of medication use. Thus, in an individual patient, whether it is medication induced often remains uncertain. The pathogenesis remains unknown.

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Section: Resultsmentioning

confidence: 99%

Gynecomastia and drugs: a critical evaluation of the literature

Nuttall

Warrier

Gannon

2015

Eur J Clin Pharmacol

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“…As with the other aldosterone antagonists, it competitively inhibits the binding of aldosterone to the mineralocorticoid receptor, blocking the biological effects of aldosterone. 19 On the other hand, biotransformation of spironolactone leads to the synthesis of other metabolites that increase the rate of peripheral conversion of testosterone into estradiol 20 and/or interfere with the androgen receptor, 21 leading to the appearance of gynecomastia in some patients, a phenomenon much less frequent with canrenone. Aldosterone antagonists have some inhibiting activity on aldosterone synthesis as well.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of canrenone in patients with preascitic cirrhosis

et al. 2002

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In patients with cirrhosis and portal hypertension, standing induces a reduction in cardiac index (CI) and an increase in systemic vascular resistance index. Our previous studies indicate that this abnormal hemodynamic response to standing is due to an altered myocardial function, because cirrhotic patients are unable to compensate for the reduced preload with an increase in left ventricular (LV) ejection fraction (EF) and stroke volume. To evaluate whether the cardiac dysfunction in cirrhosis is influenced by canrenone, an aldosterone antagonist, 8 patients with preascitic, nonalcoholic cirrhosis, and portal hypertension underwent echocardiographic assessment of LV function and systemic hemodynamics and determinations of plasma volume, urinary sodium excretion, and plasma renin activity T he hemodynamic pattern of cirrhosis with portal hypertension, with high blood volume and cardiac output and low systemic vascular resistance (SVR), is thought to play a major role in the development of sodium retention and ascites. 1 Bernardi et al. [2][3][4] showed that this hemodynamic pattern occurs only in the supine position; standing is associated with a reduction in cardiac output and an increase in SVR, that is, a "normalization" of systemic hemodynamics. This response to standing is quite different from that of healthy subjects, who do not show any appreciable changes in either cardiac output or SVR. 2-4 However, "normalization" of systemic hemodynamics during standing is associated with activation of vasoconstricting and sodium retaining systems. 3,4 In patients with preascitic cirrhosis, sodium retention occurs only during standing, 3 whereas, in those with ascites, it occurs in either position but worsens during standing. 4 We recently evaluated cardiovascular function in healthy subjects and cirrhotic patients with ascites and hyperdynamic circulation. 5 When supine, patients had increased left ventricular ejection fraction (LVEF) and cardiac index (CI) and reduced LV end-systolic volume index (LVESVI) and SVR. On standing, LV end-diastolic volume index (LVEDVI) decreased in all subjects. Healthy subjects maintained CI and stroke volume index (SVI) by decreasing LVESVI. In contrast, cirrhotic patients experienced a fall in SVI and CI and a disproportionate increase in arterial elastance (Ea), despite marked

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“…In vivo spironolactone plays its aldosterone antagonist role only after its conversion into canrenone by the liver [33][34][35]. Thus, the failure to demonstrate an in vitro inhibitory effect of spironolactone is easily explainable by the absence of such a conversion in our tubule suspensions.…”

Section: Neither the Presence Of Spironolactone Nor Canrenone Nor Cmentioning

confidence: 99%