What is known about HMG-CoA reductase inhibitor (statin) induced erectile dysfunction? Is there any

Fråga: What is known about HMG-CoA reductase inhibitor (statin) induced erectile dysfunction? Is there any difference between the statins concerning erectile dysfunction? The question concerns a 49-year-old man who had a brain stem infarction in November 2004. His triglycerids were 3.4 and LDL-cholesterol 4.4. He is now treated with atorvastatin (Lipitor) 10 mg per day and has developed a partial erectile dysfunction. His blood lipids have now normalised with triglycerids 1.7 and LDL-cholesterol 2.7. In Fass (the Swedish catalogue of approved medical products) it is stated that impotence is a known adverse effect to atorvastatin therapy.

Sammanfattning: In the large 4S-study, no significantly increased risk of erectile dysfunction in patients treated with simvastatin was seen. However, there are reports of impotence in connection to statin therapy. I many cases erectile function was restored upon discontinuation of the drug. A possible connection cannot be ruled out. There are no studies comparing the risk of erectile dysfunction for the different statins.

Svar: Erectile dysfunction has not been reported in the large randomised controlled trials. According to data from the Scandinavian simvastatin survival study, were 4444 patients with coronary heart disease were randomised to receive either simvastatin or placebo, impotence or sexual dysfunction were reported by 37 patients receiving simvastatin and 28 patients receiving placebo. This difference was not significant (1).

In a study, 678 men referred to a clinic for hyperlipidemia were questioned about sexual disorders in a complete physical examination. Men treated with antilipemic drugs (statins, resins or fibrates) were matched with those untreated. Patients with other risk factors for impotence, such as previous myocardial infarction, angina pectoris, stroke, diabetes and use of antidepressants or neuroleptics were excluded. More men in the treated group reported impotence (12.1%) than in the untreated group (5.6%). There was a significant association between pravastatin and simvastatin (the statins used in the study) and erectile dysfunction (odds ratio 1.51; 1.26-1.80) (2).

A few case reports have been published. In a brief report, five men with coronary artery disease developed impotence within one week after initiating therapy with simvastatin or increasing the dose to 20 mg. Within one week of stopping treatment, the sexual function had returned to normal. Two of the patients started treatment again, with recurring impotence, which again resolved after discontinuation. Four patients were then given fluvastatin, with similar effect on the cholesterol, and had no sexual difficulties during 12-36 months follow up (3). Another case, with a man with severe coronary artery disease, first lovastatin and later pravastatin induced impotence. After withdrawal the patient regained sexual function (4).

In 1996 the Australian Adverse Drug Reactions Advisory Committee had received 42 reports of impotence in association to simvastatin therapy. In 35 of these, simvastatin was the only drug implicated. Recovery was only mentioned in 29 reports, and among these 14 had recovered after withdrawal and for the remaining 15 the problem remained at the time of reporting. In four patients the problem recurred on rechallenge (5). Another 83 reports of statin induced erectile dysfunction to the UK Committee on Safety of Medicines have been identified (6). The Swedish adverse drug reactions register has received a total of 14 reports of sexual disturbances in men for the whole group of statins (simvastatin 8, atorvastatin 6 and fluvastatin 1) of a total of 1003 reports. In eleven of these cases the erectile function was restored after withdrawal and in three cases a reexposion was made and the problems recurred (7).

In one study, improvement of erectile function in eight out of nine men, with hypercholesterolemia as the only risk factor, was seen when treated with atorvastatin (8).

Hypercholesterolemia itself is a risk factor for erectile dysfunction. It is therefore hard to evaluate whether the effects seen are due to the disease or to the treatment. Since withdrawal of treatment has restored the erectile function in many cases, a connection between statins and erectile dysfunction might be possible. However, based on the widespread use of statins worldwide and the relatively few cases reported, this seems to be an uncommon problem, though there is a risk that this problem may be under-reported. There is no known mechanism for this possible adverse effect.

In the present case, the brain stem infarction may be a contributing factor for the patients´ erectile dysfunction. If no other explanation for the symptoms can be found, we recommend that the present case be reported to the regional adverse drug reaction monitoring centre.