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International Journal of Impotence Research (1997) 9, 17±26 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00

The in¯uence of on erectile function

W Meinhardt1, RF Kropman2, P Vermeij3, AAB Lycklama aÁ Nijeholt4 and J Zwartendijk4

1Department of Urology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; 2Department of Urology, Leyenburg Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands; 3Pharmacy; and 4Department of Urology, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands

Keywords: impotence; side-effect; ; antihypertensive; ; erectile function

Introduction stopped their antihypertensive treatment over a ®ve year period, because of side-effects on sexual function.5 In the registration procedures sexual Several physiological mechanisms are involved in function is not a major issue. This means that erectile function. A negative in¯uence of prescrip- knowledge of the problem is mainly dependent on tion- on these mechanisms will not always case reports and the lists from side effect registries.6±8 come to the attention of the clinician, whereas a Another way of looking at the problem is drug causing will rarely escape the atten- combining available data on mechanisms of action tion. of drugs with the knowledge of the physiological When erectile function is in¯uenced in a negative mechanisms involved in erectile function. The way compensation may occur. For example, age- advantage of this approach is that remedies may related penile sensory disorders may be compen- evolve from it. sated for by extra stimulation.1 Diminished in¯ux of In this paper we will discuss the subject in the blood will lead to a slower onset of the erection, but following order: may be accepted. A mild `venous leak' can be compensated by extra in¯ow of blood2 and the Physiology: suboptimal rigidity may be accepted. Therefore a Penile erection negative in¯uence of medication on the erectile Control mechanisms function will not always lead to a complaint. hormonal system The problems themselves for which drugs are prescribed, such as cardiovascular disease, psycho- peripheral nervous system sis, depression, diabetes mellitus may have a Cavernous function negative effect on sexual and erectile function. In Prescription drugs: this situation the already compromised system is more vulnerable to adverse effects of medication. psychotropic drugs Erroneously the erectile dysfunction may be attrib- cardiovascular drugs uted to the disease, instead of the medication. In miscellaneous drugs geriatric patients, who often use several drugs to treat erectile disorders at the same time, the issue is even further compli- Guidelines for clinical practice cated.3 Many patients will not discuss their sexual problems when not invited to do so. In clinical practice all this will result in an underestimation of Penile erection the drug factor in impotence. It has been estimated that the drug factor plays a role in 25% of patients An extensive review on the physiology of penile seeking advice for erectile dysfunction.4 Patient erection has been published by Andersson.9 The compliance concerning correct medication usage, initiation of an erection is a neurogenic event. The is, among other things, dependent on side-effects. In impulses may originate from the brain (as in REM a large follow-up program 8.3% of the male patients erections) or derive from sacral re¯exes (as in some paraplegic patients). In normal circumstances Correspondence: Dr W Meinhardt. it will be a combination of both. Dilatation of the Received 25 July 1996; accepted 21 October 1996 arteria cavernosa and the helicine arteries is con- The in¯uence of medication on erectile function W Meinhardt et al 18 trolled by the well described neural regulation The negative effect of castration on erectile function mechanisms. This is however not suf®cient for the may be secondary to this. Erections during REM development of a rigid erection, since there are sleep are inhibited by castration, suggesting an shortcuts to the venous channels and the resistance in¯uence on the central nervous system.14,15 of the lacunar spaces in the corpora cavernosa The adult corpus cavernosum hardly has any depends on smooth muscle tone. Relaxation of the receptors for , while in children testos- smooth muscle cells is necessary for the expansion terone induces growth of the penis, rather than of the corpora, this is initiated by parasympathetic erections.16 It has been shown that the hormonal impulses. Sympathetic tone needs to be reduced, manipulation preceding gender reassignment (phar- since this causes contraction of the smooth muscle macological castration) lowers the amount of nitric cells. The search for non , non oxide synthase (NOS) in the corpus cavernosum (NANC) transmission of the impulses of the nervous tissue.17 In a model mediated erectile system to the smooth muscle cells has drawn activity was a testosterone dependent event, while attention to nitric oxide (NO) as an initiator of a in another rat model it was shown that dihydrotes- cascade of chemical events that results in relaxation tosterone levels positively correlate with the amount of all the smooth muscle cells of the corpora.10,11 of NOS in the corpus cavernosum.18,19 However, After the ®rst impulses, the scarcely innervated after castration the local mechanisms leading to network of endothelial cells and smooth muscle penile smooth muscle relaxation are not impaired, cells take care of their own coordination in order to possibly since compensation occurs by lowering of relax all at the same time. This is accomplished the sympathetic tone.20 through tight junctions and gap junctions. Free The testosterone serum level is mainly deter- in¯ow of blood is allowed in the lacunae, ®nally mined by the epiphyse/pituitary/testes feedback resulting in such a tumescence that out¯ow of blood system. and - in¯u- will be stopped by compression of the venous ence the testosterone serum level via this system. channels between the distended corporal tissue High prolactin levels also lower the testosterone and the tunica albuginea. This leads to rigidity of production. Hyperprolactinaemia may be drug in- the penis that may be further enhanced by contrac- duced. , estrogens, , a- tions of pelvic ¯oor muscles, compressing the crurae , and the are of the corpora cavernosa and building a pressure known for this. The elevation of prolactin serum that is higher than the systolic .12 levels is usually mild and not accompanied by a In¯ow of blood to the corpora cavernosa is minimal decrease in serum testosterone levels. In absence of at that point. The erection comes to an end by a low testosterone serum level the relation of renewed contraction of the smooth muscle cells, hyperprolactinaemia and impotence is unclear and initiated by sympathetic impulses and by the withdrawal of the culprit drug maybe disappointing production of substances such as endotheline-1, because of other organic factors determining the F2a and tromboxane A2 by the erectile dysfunction.21 endothelial cells.9,13 This will allow venous out¯ow Some drugs have an unexpected anti- by decompression of the subtunical venous plexus. effect such as H2-antagonists and some drugs. Effects on the testosterone levels have been described of beta blockers, and digoxin, the practical value of these reports is Control mechanisms unclear.22±24

Several control mechanisms play a role in sexual behavior and erectile function. Many have effects on Central nervous system the central nervous system as well as on the cardiovascular system. There is an analogy in the responses of blood vessels to these regulation Emotional and cognitive factors in¯uencing sexual mechanisms and the responses of the tissue in the behavior and erectile function are beyond the scope corpora cavernosa. of this review. Several parts of the brain are involved in sexual function and already on this central level integration with autonomous regulation of other body functions is present. The brain may inhibit or Hormonal system facilitate the spinal mechanisms leading to an erection. Among others, the hypothalamic and limbic pathways are intensively studied. The medial The exact role of testosterone on erectile function is preoptic hypothalamic area, in contact with the not well de®ned. The negative in¯uence of castra- paraventricular nucleus of the is tion on is regularly seen in clinical practice. important for autonomic and neuroendocrine inte- The in¯uence of medication on erectile function W Meinhardt et al 19 gration.9 systems and serotoninergic mechanisms of homotropic and heterotropic inter- systems play a major role in sexual behavior and action can be in¯uenced by drugs. The pelvic erectile function.25 For several psychopharmaca ganglions are also the site where neuromodulation these systems are the speci®c target.26 Apomor- takes place by various endogenous substances phine, a central , is effective in (, adenosine, , and enhancing sexual behavior in the animal model as dopamine) at their speci®c receptors.29 At the well as in .27 For this effect testosterone peripheral level the existence of different needs to be present.28 There is evidence that this subtypes and the relative af®nity of drugs to these effect is also dependent on oxytocine release.9 receptors makes prediction of the resulting effect of Dopamine also has cardiovascular effects, mediated drugs on the corporal smooth muscle tissue compli- by several distinct types of receptors that vary in cated. their af®nity. In low concentrations dopamine acts on vascular D1 receptors, leading to vasodilatation. In somewhat higher doses it activates the beta-1 adrenoceptors, whereas at high concentrations va- Sympathetic nervous system soconstriction is effectuated via activation of vas- cular -1 adrenoceptors.29 The smooth muscle has a resting tone that is mainly Of the serotoninergic system mainly the 5-HT , 1A governed by tonic alpha receptor stimulation.34 5-HT and the 5-HT receptor subtypes play a 1C 2 Reduction of sympathetic tone is important to facilitory role in sexual behavior and initiate a reaction, but does not result in penile antagonists have a negative in¯uence.25,26 On this erection. Bilateral sympathectomy does not cause level the explanation may be found why such a priapism. Psychogenic inhibition of erections is marked difference was shown between the effec- mediated by the sympatic nerves and by circulating tiveness of several anti-serotoninergic agents in catcholamines.35 Ejaculation is controlled by the impotence treatment.30 sympathetic nervous system. Thereafter detumes- For a stimulatory effect of 5-HT 1A cence is initiated by the sympathetic pathway, testosterone needs to be present.31 Cardiovascular inducing contraction of the smooth muscles of the effects of serotonine may be constricting or dilating, corpora cavernosa and so allowing out¯ow of blood. depending on the type of receptor activated, while Reviewing the subject of receptors, Andersson serotonine also in¯uences the release of noradrena- concludes that for the cavernosal tissue alpha-1 line from adrenergic nerves and stimulates endothe- adrenoceptors predominate functionally, alpha-1A lial cells to release and NO.29 and alpha-1C being more numerous than alpha-1B Noradrenergic neurons also play a role in the adrenoceptors.9 Alpha-2 adrenoceptors predominate central regulation of sexual function.9 Methyldopa, in the cavernous artery.9 The beta-2 adrenoceptors, an older , may so be respon- although present, are not supposed to be function- sible for erectile dysfunction.6 The selective alpha-2 ally important.36 For impotence treatment with adrenoceptor antagonist may improve drugs applied intracavernously (i.c.) the alpha libido and its main effect in vivo is probably on the adrenoceptors are an important target.37 Blockade central nervous system.32 Of the central neurotrans- of alpha adrenoceptors by medication may cause mitters oxytocin, ACTH and related peptides, priapism.38 prolactin, gamma-aminobutyric acid and endor- phins are all implicated in the regulation of sexual behaviour and erectile function.9 Stress may in¯u- ence the production of endogenous which Parasympathetic nervous system has re¯ections on the hypothalamic-pituitary-lutei- nizing hormone axis.33 Transection of the nervi erigenti leads to impotence because the induction of smooth muscle relaxation, Peripheral nervous system followed by high in¯ow of blood, is a parasympathic event.39 The parasympathetic impulse however is not only the result of direct cholinergic transmission Somatic pathways are important for sensitivity of by to receptors on the the penile and the contraction of the pelvic smooth muscle cells in the corpora cavernosa. It is ¯oor muscles. The autonomic nervous system is supposed to have its effect by inhibiting the release essential for erectile function. The of of noradrenaline from sympathetic nerve endings the autonomic system has been extensively studied. and by the release of Non Cholinergic Non Adre- At the ganglionic level (the nicotinic acetylcholine nergic (NANC) transmitters from the parasympa- receptor) the system will respond to drugs in the thetic nerve endings and from the endothelial usual way. At this site integration of parasympa- cells.9,40 NO is one of the main NANC transmit- thetic and sympathetic impulses takes place and the ters.10,11 The in¯uence of medication on erectile function W Meinhardt et al 20 Cavernous tissue function therapy, for example the use of the NO donors linsidomin and of calcitonin gene related pep- tide.55,56 The data from research of oral medication From his experience with i.c. therapy acting on these systems becomes available Goldstein41 formulated a cascade theory, in which now.53,54,57 he combines pharmacologic events with physiology and anatomy. After an i.c. injection with vaso-active drugs relaxation on that site in the cavernous tissue Prescription drugs leads to local increase of blood in¯ow. This if followed by activation of endothelium-mediated relaxation factors, the zone of muscle relaxation is Psychotropic drugs enlarged, leading to local increase of blood in¯ow etc. If any part of the corpora cavernosa is not completely relaxed, venous return is not suf®ciently Especially antipsychotic and drugs stopped and rigidity is suboptimal or of short are known for their side effects on erectile func- duration. This is the equivalent of the clinical tion.6±8 In clinical practice the patients in need of concept of `venous leakage' that may be quanti®ed these drugs may not be ideal candidates to have by cavernosometry.42 The pathways by which the their sexual performance evaluated. Much is known smooth muscle cells communicate and the role of from animal studies. Side effects may be due to the endothelial cells of the corpora cavernosa are adrenergic, , dopaminergic or seroto- under investigation. ninergic effects.58 Other psychotropic drugs such The smooth muscle cells are in contact with each as , are reported to cause impo- other through gap junctions. In cavernous tissue tence. Maybe this effect is simply the result of they consist mainly of and sedation.6 Unexplained is the ®nding that channels.43,44,51 In this way integrated action is when combined with benzodiazepines is associated possible, since this allows for relatively unimpeded with sexual dysfunction in almost half of the intercellular transit of current carrying and patients.59 transit of small metabolites and second messengers and have an as inositol triphosphate, cyclic adenosine monopho- effect on the dopaminergic and the serotinergic sphate (cAMP) and cyclic guanosine monopho- central nervous system that may be stimulating or sphatase (cGMP). For more details we refer to inhibiting. The combination of stimulating central excellent reviews on this matter from Andersson effects with periferal alpha-blocking properties may and Christ.9,45 induce priapism, because the alpha receptors in the Several products of the nerve endings and the cavernous tissue are important for contraction of endothelial cells can initiate smooth muscle relaxa- smooth muscle cells and so the initiation of tion, such as NO, vasoactive intestinal peptide (VIP), detumescence. The most reported antidepressant , calcitonin gene related peptide, drug that causes priapism is .60 This substance P, prostanoids.46,47 Especially NO has antidepressant drug has been applied i.c. and drawn much attention as an important regulator of induced smooth muscle relaxation.61 It is also smooth muscle tone in the corpora cavernosa.10,11 known for its ability to improve libido.62,63 Clomi- NO is produced by autonomic nerve endings and by pramine, a antidepressant that combines endothelial cells from L-arginine and molecular O2 serotonin inhibitor properties with alpha by NO synthase (NOS). NOS is available in several blocking properties is more isoforms and its production can be stimulated in effective for treatment of premature ejaculation, than several ways.48 In chronic hypoxic states NO for treatment of erectile dysfunction.64 formation is reduced.49 has been associated with erectile dysfunction as NO activates guanylate cyclase, the conversion of well as with the return of .8,65 More GTP to cGMP lowers the calcium concentration and consistent is its postponing effect on the ejacula- leads to relaxation of the smooth muscle. In addition tion.66 When erectile dysfunction is caused by a to the cGMP pathway, activation of NA/Ka-ATPase drug it may be may also play a role in the relaxation of corpus rational to try the patient on trazodon or ¯uoxetine cavernosum tissue by NO.50 Cyclic nucleotide instead.67 However one must consider the possibi- phosphodiesterases (PDE) are that hydro- lity that erectile dysfunction might persist in the lyse cGMP and cAMP to monophosphates. PDE may presence of an increased libido. be blocked by pharmaca, for example papaver- Of several antipsychotics the alpha-blocking ine.51,52 Several PDE subtypes can be identi®ed. In properties are known, so in case of drug induced the corpora cavernosa PDE5 is predominant and this impotence one might consider an alternative drug subtype is blocked by sildena®l.53,54 These insights with stronger alpha-blocking properties, a higher in the physiology of the corpus cavernosum have af®nity for the alpha-1 receptor. The af®nity for the already led to new possibilities for i.c. injection alpha-1 receptor in decreasing order is: , The in¯uence of medication on erectile function W Meinhardt et al 21 levopromazine, , zuclopentixol, haloper- ment as far as erectile function is concerned.74 On idol, , .68 When the alpha- cavernous smooth muscle they have a relaxing blocking properties induce priapism, an alternative effect.75 When injected i.c. they induce erections.76 antipsychotic must be used with a lower af®nity to However they are reported as responsible for erectile the receptor. The susceptibility of the patient may dysfunction.7,8 This may be due to the drop in blood change with time and also co-medication with pressure, provoking a sympathetic nervous system alpha-blocking properties must be considered. Re- response.76 openers, with pina- current priapism due to depot zuclopentixol has cidil as well studied example, do show an erecto- been reported.69 genic effect when directly applied to the corporal tissue. But taken orally potassium channel openers are not suitable for impotence treatment because of Cardiovascular drugs insuf®cient tissue selectivity and the stimulation of the sympathetic nervous system.77±79 is an exception in this respect, being applied as ointment To initiate an erection a generous in¯ow of blood is for induction of tumescence, while taken orally it needed. The classical combination of claudicatio has been reported to cause priapism.80 intermittents and impotence, due to stenosis of The above mentioned mechanisms may play a central arteries is known as the Leriche syndrome. role in impotence caused by ACE-antagonists. Since Arteriosclerosis is accompanied by degenerative converting (ACE) inhibitors changes in the corpus cavernosum.70,71 These may be responsible for , a hormonal changes make the veno-occlusive mechanism less in¯uence also seems possible.81 The older cardio- effective. Dysfunction of the corpus cavernosum vascular drugs have important effects on the central tissue is the main cause of `venous leakage'.42 The nervous system, for example methyldopa in¯uen- combination of in¯ow reduction with a diminished cing central alpha-2 activity.6 Erectile disorders possibility to trap the blood in the penis, is caused by have been reported, the mechan- detrimental for erectile function.2 The patient in ism is unknown. Digoxin-associated impotence has need of cardiovascular drugs already has a vulner- recently been studied extensively and the under- able erectile function and they will be more lying mechanism was shown to be inhibition of the susceptible for medication induced erectile dys- Na/Ka-ATPase pump.82 The authors even remarked function. In addition to this, many cardiovascular that digoxin might prove useful to inhibit erectile drugs have a direct in¯uence on the autonomous activity, for example after penile surgery. innervation of the penis. Betablocking agents are In only a few comparative studies of different known for their negative effects on erectile function. bloodpressure lowering regimes sexual function has This may be due to their effect on the beta been evaluated. In a trial with 626 men in need of adrenoceptors in the corpora cavernosa, but these antihypertensive treatment, 44% had a complaint are underrepresented in the cavernous tissue (alpha on sexual functioning at the start of the trial. Half of receptors outnumber beta adrenoceptors 10±1).36 these complaints concerned erectile function. The Another explanation is a change in balance between group on the ACE inhibitor captopril had as many alpha and beta sympathetic in¯uence, resulting in patients improving as deteriorating (18%), while the insuf®cient antagonism of the alpha-1 vasoconstric- patients on the beta adrenoceptor blocker proprano- tion.72 When betablocking agents prescribed for high lol and the patients on methyldopa improved in 9% bloodpressure cause impotence, an alpha-blocking and worsened in 25%. Of the patients who needed agent may be a good alternative. Even alphablocking additional diuretics later in the trial, the patients on agents have been implicated as the cause of erectile and a had extra problems with dysfunction.7,8 This may be due to the lowering of erectile function.83 A comparison between a diuretic the bloodpressure as such.73 Possibly making these () and an alpha adrenoceptor patients more vulnerable for a steal phenomenon. blocker () showed that nocturnal erections Alphablocking agents have an effect on the ejacula- were more rigid after the use of the alpha adreno- tion, they may delay ejaculation or cause a retro- ceptor blocker.84 In a comparison of chlothalidone, grade ejaculation and so give rise to secondary , , , enapril and (psychogenic) erectile dysfunction. Alphablockers placebo for treatment, pre-existing interfere with the sympathetic induced detumes- problems with erectile function improved with all cence and may cause priapism. patients on doxazosin (an alpha blocking agent).85 Several vasodilators have a relaxing effect on the Often cardiovascular drugs have a negative effect on corporal tissue when applied intracavernously or erectile function, but disease related problems and even topically, but this effect is not obvious when drug related problems are hard to distinguish in the these drugs are taken orally. Many vasodilators act clinical setting. Any cardiovascular drug may cause upon the calcium and potassium channels. Calcium erectile dysfunction. ACE inhibitors, calcium chan- reentry blocking agents are considered safe treat- nel blockers and alpha blockers should be consid- The in¯uence of medication on erectile function W Meinhardt et al 22 ered as alternatives in case of drug induced alpha-blockade. In a double blind study good impotence.74 responses were noted in 21 and 13.8% for 6 mg yohimbine three times daily and placebo.95 This type of study is necessary before any claim can be made for this indication. Alpha-2 adrenoceptor Miscellaneous drugs blockade as such is insuf®cient for impotence treatment. Recently a study with more than 300 patients using placebo or delequamine orally was 96 Histamine H2-antagonists (used to lower stopped because no bene®ts could be proven. secretion) are related to impotence. H1, H2 and H3 Alpha2-blockade may be rational only in the young- receptors have been found in the corpus caverno- er age group with `pure' psychogenic impotence.97 sum and stimulation leads to contraction of the The combination of central effects on the seroti- 86 smooth muscle cells. H2 receptors are not con- nine system combined with periferal alpha adreno- sidered functionally important in the corpora and ceptor blocking properties as is seen in trazodone, 98 H2-antagonists applied i.c. have no effect on erectile has been advocated for oral impotence treatment. function.86 Therefore the explanation of erectile In a double blind placebo controlled trial we were dysfunction due to H2-antagonists is probably their unable to detect any bene®cial effect beyond the anti-androgenic effect.87 Since these drugs are in the placebo effect.99 Combining drugs may give syner- top-ten of prescription drugs the problem is relevant gistic effects. The combination of 50 mg trazodon in spite of the probably low frequency in which it with 15 mg yohimbine has recently been reported becomes manifest. Cimetidine was the ®rst drug useful in a group of patients without physical from this class associated with impotence, but there abnormalities detectable. The responders had suf- is no reason to assume the other H2-antagonists are fered impotence for a signi®cant shorter period free of this problem.8,88 When it occurs, the medica- before treatment was started (6 vs 18 months).100 tion must be changed to a completely different class , a , can induce of drugs, for example antacids. erections in patients who have no organic problems, of the nonsteroid anti-in¯ammatory but it has many side effects.101 The antagonist type (NSAID) are consistently reported as respon- has been tried on idiopathic impotence sible for erectile dysfunction.7,8 Several prostanoids patients, with positive effects only on the self- are synthesized in the corpus cavernosum and they reported early-morning erections.102 Presently trials have various effects on the smooth muscle.89 This are conducted with drugs that have their rationale in may explain the negative effects of some NSAIDs. In the new insight in corpus cavernosum physiology. practice the problem is not frequently seen, taking The nitric oxide precursor 1-arginine has been into account that these drugs are taken very often. tested, however the preliminary favorable data need Anti-, prescribed for cancer, con®rmation.57 A trial with oral medication that will commonly lead to impotence. This effect is inhibits type V cGMP-speci®c phosphodiesterase, related to lowering testosterone to castration level UK-92,480 (sildena®l), showed favourable results in which is caused by LHRH-agonists and by steroidal impotence patients with no known organic antiandrogens. When the patient cannot accept this cause.53,54 side effect, it is possible to treat them with antiandrogens, or treat them intermit- tently.90±92 Whether these approaches are oncologi- cally safe, has still to be established. , a Guidelines for clinical practice drug that blocks the conversion of testosterone into and is used for symptomatic It would be ideal to obtain information on the sexual benign prostate hyperplasia, has caused impotence function of any patient before medication is pre- in 3.7% of the cases.93 Recently some doubt is cast scribed. Once the patient has been asked about it, he on the notion that dihydrotestosterone is not knows his doctor is interested and the issue can be necessary for erectile function.19 discussed in the future. When the patient complains about impotence after exposure to a drug, ®rst of all the exact nature of the complaint must be estab- lished. Ejaculation disorders must be differentiated Drugs to treat impotence from erectile failure. (Ejaculation disorders are also frequently drug related.) The time relationship between the start of the medication and the start of Extensive reviews, for oral medication and for drugs the complaint must be established. When the drug is for i.c. use, were published in this journal.32,94 The known to be related to erectile disorders, see Table alpha-2 adrenoceptor yohimbine has been used for 1, an alternative drug may be tried. Suggestions are its libido enhancing and its erection improving given in the earlier sections. When the drug is not properties. The main pharmacological property is known to cause impotence, detailed follow-up after The in¯uence of medication on erectile function W Meinhardt et al 23 Table 1 Medication that is associated in the literature with erectile dysfunction. Based on Reactions (Weekly) January 1991 to January 1996 and References 8, 104 and 105. acebutolol metronidazole metyrosine allopurinol clozepam minoxidil acetate morphine alu®brate cyclosporin A hydantoins naltrexone hydrochlorothiazide anisotropine desmethylimipramin hydroxycholorquine hydroxyprogesterone aurothioglucose norethindrone norlutin bendro¯umethiazide dibenzepine dichlorphenamide interferon benzbromarone dicyclomine benzhexol diethylpropion diphenydramine benztropine digoxin betamethasone beza®brate disul®ram oxyphenonium paramethasone leuproreln lisinopril bromocryptine lithum bromperidol enalapril estrogens pericyazine ethionamide eto®brate buserelin busulphan fen¯uramine medroxyprogesterone phenelizine feno®brate melperon ®nasteride butizide ¯ecainide ¯uanisone camylo®n ¯uphenazinc phenytoIÈne canrenoate-K ¯unarizine mesterolone captopril ¯unitrazepam ¯uocortolone methadilazin pimozide ¯uoxetine ¯upentixol ¯urazepam methanteline pipoxolan chloorprothixen ¯uspirilene ¯utamide ¯uvoxamine gem®brozil methyldopa gestagenen gestonoron caproate pramiverine theofyllinate cimetidine glycopyrrolat prazosin glycopyrronium goserelin clo®brate metoclopramide prednylidene

(continued) The in¯uence of medication on erectile function W Meinhardt et al 24 Table 1 (continued)

probucol ramipril testosterone tri¯uoperazine thiabendazole tri¯uperidol rauwol®a thiazinamium tri¯upromazine trihexyyphenidyl proguanil thioridazine trimeprazine proloniumiodide thiothixene trimetaphan thiotixene triptorelin propanolol spironolactone propantheline stilbestrol trazodone vincristine triamcinolone protionamide

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