Statins and erectile dysfunction: results of a case/non-case study using the French Pharmacovigilance System Database.

BACKGROUND: HMG-CoA reductase inhibitors, more commonly called statins, are widely used in the pharmacological management of hyperlipidaemias. The most common adverse drug reactions (ADRs) of statins are muscular. Other reported ADRs of statins along with other lipid-lowering drugs, namely fibrates, include erectile dysfunction (ED). The relationship between ED and exposure to statins has not clearly been established even though a number of significant case reports have associated ED with exposure to statins.

OBJECTIVE: To investigate the association between exposure to statins and the occurrence of ED on the French Pharmacovigilance System Database.

METHODS: Within the French Pharmacovigilance System Database, the case/non-case method was used to measure the disproportionality of combination between a statin and ED. Cases are defined as those reports corresponding to the ADR of interest (i.e. ED) and non-cases are all reports of ADRs other than that being studied. The study period was from 1 January 1985 to 31 December 2006, limited to males aged 13-80 years. We estimated the association between ED and statins by calculating a reporting odds ratio (ROR) of exposure to each drug, with its 95% confidence interval (CI).

RESULTS: Among the total of spontaneous reports selected (110 685), exposure to statins was identified in 4471 cases (4%), of which 51 reports (1.1%) concerned ED, whereas 431 (0.4%) cases of ED were found in the 106 214 reports without exposure to statins (p < 0.0001). The mean delay of onset of ED after starting statins, known for 19 cases, was 62 days (median 29 days). In 56.9% of cases, recovery occurred after withdrawal of statin, and rechallenge was positive in five cases. The association was statistically significant for all statins (adjusted ROR [aROR] = 2.4; 95% CI 1.8, 3.3), simvastatin (aROR = 2.6; 1.6, 4.1), atorvastatin (aROR = 3.4; 2.1, 5.4) and rosuvastatin (aROR = 7.1; 2.6, 19.4) [p < 0.001 for all] but not for pravastatin and fluvastatin. We did not find any relationship between the occurrence of ED and the daily dose or the duration of exposure to statins (data not shown). Assessment of the association between drugs other than statins known to be at risk of ED confirmed a significant association for finasteride (aROR = 14.5; 95% CI 8.3, 25.4), fibrates (aROR = 3.6; 2.6, 5.1), beta-adrenergic receptor antagonists (aROR = 1.5; 1.01, 2.1) and tricyclic antidepressants (aROR = 2.0; 1.2, 3.4) [all p < 0.05].

CONCLUSION: Despite some methodological limitations, the present study suggests that statins may induce or worsen ED in accordance with other data. Further pharmacoepidemiological studies are necessary to confirm this conclusion and to improve the precision of the prevalence and/or the risk factors of this ADR.