We read with great interest the work by Koman et al (1) dealing with the possible association between intrathecal clonidine and erectile dysfunction (ED). Indeed, the authors reported on the case of a 52-year-old man who presented with a history of chronic neuropathic pain treated with an intrathecal application of morphine for many years, but without considerable relief. When clonidine was applied in combination with morphine, the patient experienced a significant pain relief, but showed

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... nsion and ED, which disappeared after clonidine withdrawal, clearly demonstrating a cause-and-effect relationship. Erectile dysfunction is a highly prevalent problem increasing with age, as well as the major men's sexual concern. ED shares common risk factors with cardiovascular diseases, i.e. diabetes mellitus, dyslipidemia, smoking, hypertension, absence of physical exercise and obesity, and may be secondary to endocrine-metabolic and neurological disorders or due to psychogenic factors. Moreover, many different drugs can cause ED by affecting sexual hormone levels, neurotransmission, or blood circulation. Among them, antidepressants (especially those acting on the serotoninergic pathways), neuroleptics, and antihypertensives are the drugs most often associated to sexual dysfunction (SD), including ED. In particular, centrally acting antihypertensive agents such as methyldopa and clonidine, nonselective beta-adrenergic blockers, and potassium-sparing diuretics are those most often associated with SD; thiazide diuretics cause ED but may otherwise play a minimal role in other SD; alpha-adrenergic blockers, angiotensin converting enzyme inhibitors, and calcium channel blockers have little adverse effect on sexuality (2). Drug-related sexual side effects are strictly dosedependent and disappear after the drug has been withdrawn. However, drugs dosages used for spinal intrathecal administration are usually low as to minimize side effects, including SD. Nevertheless, it has been reported that intrathecal baclofen may reversibly compromise erection and ejaculation particularly at higher doses (3) . To the best of our knowledge, intrathecal clonidine-induced ED has never been described before Koman et al's report (1) . Clonidine functions as a sympatholytic by stimulating presynaptic 2-receptors leading to decreased release of norepinephrine at both central and peripheral adrenergic terminals. It has also been proposed that the antihypertensive effect of clonidine is partly due to agonism on the I1-receptor or imidazoline receptor, which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure (4). In addition to its influence on the autonomic nervous system, it is well established that clonidine is an effective analgesic, and this is also attributable to its 2-agonist activity. Interestingly, Clark and Smith (5) demonstrated a dose-dependent inhibition of erectile reflexes, with inhibition occurring at doses lower than those required to induce copulatory dysfunction. Thus, it is possible that clonidine may induce ED by decreasing sympathetic outflow (with a consequent inhibition of reflexive erection) as well as diminishing libido and ejaculation, even when intrathecally administered. In conclusion, since ED-related clonidine intrathecal administration may be an overlooked and underreported problem, further prospective studies should be fostered to support this causal link.