Erectile Dysfunction and Statin Treatment in High Cardiovascular Risk Patients

H. Solomon; Y. P. Samarasinghe; M. D. Feher; J. Man; H. Rivas-Toro; P. J. Lumb; A. S. Wierzbicki; G. Jackson

Disclosures

Int J Clin Pract. 2006;60(2):141-145. 

In This Article

Discussion

ED is commonly associated with atherosclerosis.[8,9] Vascular ED can therefore be exacerbated by many of the risk factors which cause atherosclerosis, but it is also well documented that control of these risk factors with specific drug therapies can worsen or even precipitate ED. This study investigated the association of individual cardiovascular risk factors and their therapies with erectile function in a cohort of men attending cardiovascular disease clinics. In particular, it investigated the effect of statin therapy on erectile function in this group.

Over 50% of men attending routine cardiovascular disease clinics suffer from some degree of ED prior to the addition of statin therapy.[10] Similar results were obtained from the Massachusetts Male Aging Study (MMAS), which showed a prevalence of ED of 56% in men with ischaemic heart disease.[11] Statin therapy routinely recommended for cardiovascular disease has been associated with worsening erectile function. Case reports of this phenomenon with statin therapy have been previously documented.[12] Simvastatin was found to cause impotency in five men with coronary artery disease, and within 1 week of discontinuing simvastatin, sexual function was restored. The Australian Adverse Drug Reactions Committee reported 42 cases of ED associated with simvastatin.[13] In contrast, in one study in men aged 49.7 years and isolated hypercholesterolaemia [low-density lipoprotein (LDL)-C 4.3 mmol/l] as a risk factor which used penile Doppler ultrasound in a per protocol analysis of 50% of the cohort of 18 patients (n = 9), atorvastatin therapy was associated with improvement in erectile function (Sexual Health and Impotence Measurement 16→21) if LDL-C was reduced to 3 mmol/l.[14] One possible mechanism postulated was that statin lipophilicity may have an effect. Simvastatin is highly lipophilic and hence could act either centrally or induce a drug-induced peripheral neuropathy in the penile nerves. The current study confirmed the association between introduction of statin therapy but did not find any relationship with dose, cholesterol-lowering efficacy statin dose or relative lipophilicity of the statin and the extent of ED. In addition, the population in our study was 10 years older and more typical of patients with cardiovascular disease, as they had multiple cardiovascular risk factors indicating a more complex aetiology to their endothelial and ED.

A second hypothesis by which statin therapy may worsen erectile function is that it may interact with other agents that are also implicated in the causation of impotence.[12] In our study, prior to statin therapy, atherosclerotic risk factors accounted for only 20% of the variance (r = 0.45) in ED scores and were not clearly associated with ED. However, after initiation of statin therapy, this relationship strengthened to 38% (r = 0.62), and three key variables associated with ED could be defined. These were age, diabetes and (more weakly) smoking. The correlation of ED with age, smoking and diabetes is not surprising and probably reflects deterioration in endothelial function, and the associations with hypertension and diabetes are ameliorated with statin therapy ( Table 2 ) as would be expected from their actions on endothelial function. ED is more common with advancing age or diabetes.[11] The MMAS showed that the probability of ED in men with CHD increased from 39% in nonsmokers to 56% in smokers,[11] and ED is a well-known side effect of β blockers.[15,16,17]

Prior to statin therapy both ACE-Is and ARB improved ED. The relationship of antihypertensive drugs and ED is unclear,[18,19] as both ACE-Is and ARBs have been shown to improve ED in monotherapy.[17,20,21] However, another study of 101 men with hypertension found a prevalence of impotence of 26% of which 70% were associated with ACE-Is.[22] A prescribing survey study in 634 patients with diabetes and ED and 2525 without showed a similar paradoxical action with ACE-Is (RR 1.47) and a blockers (RR 1.54) when the data were analysed after correction for other drug therapies including statins, nitrates and digoxin.[18] These data suggest that cardiovascular drug interactions in the field of ED are complex and may depend on the extent of underlying atherosclerotic disease as well as the drug treatment. This may also be true for statins given the data in patients with isolated hypercholesterolaemia.[14] In addition, if either the LDL-lowering or antihypertensive dose was suboptimal then ED might result because of both disease burden and superficially drug treatment. As optimal levels for both blood pressure and LDL-C keep being redefined to lower targets in high-risk patients, this situation is far likelier to occur in patients at high rather than low cardiovascular risk. Reductions in targets imply increased doses of statins, and the extension of aggressive statin therapy from secondary to primary prevention may lead to an increase in the prevalence of statin-induced ED. This under-reported side effect may contribute to the high rates of discontinuation of statin therapy seen in practice and in clinical trials.[23]

This small study in patients at high cardiovascular risk shows that statin-induced ED is common in patients with high cardiovascular risk. Given the limitations of small study size and a clinical rather than a quantitative physiological (penile Doppler) assessment of ED, it seems that statin therapy may be associated in high-risk patients with worsening ED. It is impossible to delineate whether severity of atherosclerotic disease, drug doses or drug interactions are responsible for the effects seen in this study. Large-scale studies in high-risk patients of phosphodiesterase-5 inhibitors on quantitative measures of ED before and after achievement of optimal control of individual cardiovascular risk factors are required to clarify the pathogenesis of this effect.


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