What is known about beta-blocking agents, especially metoprolol and its relation to impotence? Can

Fråga: What is known about beta-blocking agents, especially metoprolol and its relation to impotence? Can they induce permanent impairment?

Sammanfattning: Impotence is a well-documented and relatively common side effect of propranolol. There are also reports of beta-1-selective drugs like atenolol and metoprolol, but controlled clinical trials showing the absolute risk are lacking. There is no data suggesting that beta-blocking agents could induce permanent sexual dysfunction.

Svar: Impotence is a recognized adverse drug reaction of antihypertensive therapy in general (1). Inability to achieve or maintain sufficient erection is a well-documented side effect of the non-selective beta-blocker propranolol but it has also been associated with the use of timolol, labetalol, metoprolol and atenolol (2-4). The reported incidences vary considerably as hypertension per se is associated with increased risk for male sexual dysfunction (3-6). Thereby, incidences varying between 5 and 43 per cent have been associated with propranolol treatment (3). In one study 7 out of 46 men experienced impotence during propranolol treatment (7). Sexual dysfunction was found to be dose-related and was completely reversible on discontinuation or dose reduction. Although there are a few reports of impotence induced by beta-1-selective antagonists, unquestionable evidence which might suggest an increased risk during atenolol and metoprolol treatment is still lacking. At least the risk is considerably less than with propranolol.

The mechanism of beta-blocker-induced impotence is not quite understood. Reduced penile blood flow as a result of unopposed alpha-adrenoceptor-mediated vasoconstriction. Too, decreased beta-2 vasodilation could be involved (3,6). Non-selective beta-blockers would thus have greater propensity. There are indeed case reports of restored sexual performance after switching from propranolol to atenolol (3). Central mechanisms could also be involved and it has been suggested that less lipophilic beta-blockers with less penetration to the CNS could be less prone to cause impotence and loss of libido (6). This theory has not been tested in controlled clinical trials and there is no unequivocal data in the literature suggesting that the risk for sexual dysfunction would be higher during metoprolol (more lipophilic) than atenolol (more hydrophilic) therapy.

There is no pharmacological basis to suppose that beta-blocking agents would induce permanent changes in male sexual function. As psychogenic factors play a major role in this disorder and general atherosclerosis is relatively common in hypertensive or ischemic heart disease patients, a negative dechallenge (ie sustained impotence after drug withdrawal) must be rather common among these patients. The Swedish Adverse Drug Reactions Advisory Committee (SADRAC) database did not provide any additional information on this matter.