CLINICAL PHARMACOLOGY

Drugs & Aging 2 (4): 330-344. 1992 1170-229X/92/0007-0330/$07.50/0 © Adis International Limited. All rights reserved. DRAll02

Impotence in Elderly Men John E. Morley and Fran E. Kaiser Geriatric Research Education and Clinical Center. St Louis VA Medical Center. and Division of Geriatric Medicine. St Louis University, St Louis. Missouri. USA

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Summary I. Causes of Impotence 1.1 Arterial Disease 1.2 Venous Leakage 1.3 Central Nervous System Diseases 1.4 Endocrine Disorders 1.4.1 Diabetes Mellitus 1.4.2 Others 1.5 Systemic Disorders 1.6 Psychiatric Disorders 1.7 Nutritional Disorders 1.8 Diseases of the Penis 1.9 Drug-Induced Impotence 2. Hypogonadism, Libido, Potency and Aging 3. Management of Impotence 3.1 Mechanical Devices 3.1.1 Vacuum Tumescence Devices 3.1.2 Penile Prostheses 3.2 Intracavernosal Injections 3.3 Pentoxifylline 3.4 Transdermal Nitroglycerin 3.5 Yohimbine 3.6 Phentolamine and Isoxsuprine 3.7 Zinc 3.8 Testosterone 3.9 Bromocriptine 3.10 Opioid Antagonists 3.11 Surgery 3.12 Psychological Therapies 4. A Rational Approach to the Management of Impotence

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Impotence in Elderly Men

Summary

Impotence is a highly prevalent condition occurring in 10 million American men over the age of 18 years. Alterations in vascular supply, hormonal changes with age, neurological dysfunction and the use of a variety of medications may combine and contribute to impotence. Impotence should not be considered a normal part of the aging process. Careful attention to evaluation for the aetiology of impotence will lead to making appropriate therapeutic choices.

Numerous studies have documented that erectile dysfunction occurs with increasing prevalence in men over the age of 50 years (for review see Morley & Kaiser, 1989). Aoki et al. (1987) reported that in a large group of married Japanese males, 84% under the age of 30 years were having intercourse weekly compared with only 26% of those aged 50 to 60 years and 10% of those over 60. In a large US study of individuals over 60 years of age, 73.8% of married men were sexually active (thOUgh the frequency of sexual activity was not ascertained) [Dionko et al. 1990]. Persons with decreased mobility tended to have decreased sexual activity. Recently we found that in apparently healthy males between the ages of 50 to 70 years, I in 5 were unable to obtain and/or sustain an erection adequate for intercourse (Morley et al. 1991). Approximately half of impotent males over the age of 50 years wish to have something done about their impotence (Slag et a1. 1983). While impotence increases in prevalence with advancing age it is not part of the normal aging process. However, many diseases, including those in subclinical stages that occur with increasing frequency in older persons, may lead to impotence. Before considering the causes and treatment of impotence in older males, it is necessary to draw a distinction between libido and potency. Libido refers to the desire for sexual experiences while potency is limited to the mechanical factors involved in obtaining an erection. Libido is prominently driven by psychogenic, experiential and environmental factors as well as by the availability of the male hormone testosterone. In the case of potency the major factors appear to be neurological and vascular with psychogenic and hormonal factors playing less of a role. There is an interaction between libido and erectile function, but adequate erectile

function may be seen in those with minimal libido and impotence can be present in those with high libido.

1. Causes

0/ Impotence

1.1 Arterial Disease It should be stressed that impotence in older persons is often multifactorial in aetiology. Collins et a1. (1983) reported that 65% of their impotent patients had multiple contributory factors. The major causes of impotence are outlined in table I. The most common cause of impotence in Table I. Physical causes of impotence Vascular

Arterial Venous leakage

Central nervous system disorders

Multiple sclerosis Cerebrovascular accident Temporal lobe epilepsy

Spinal cord damage

Trauma Tumour

Neuropathy

Autonomic Sensory

Endocrine disorders

Diabetes mellitus Hyperprolactinaemia Hypothyroidism Hyperthyroidism Cushing's disease Hypogonadism

SystemiC disorders

Cirrhosis of the liver Renal failure

Psychiatric disorders

Depression Widower's syndrome Performance anxiety

Nutritional disorders

Zinc deficiency Protein energy malnutrition

Peyronie's disease

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older males appears to be arterial disease (Kaiser et al. 1988a). Results of studies utilising penile blood pressure measurements suggest that atherosclerotic vascular disease causes nearly half of all the impotence in men over 50 years of age (Kaiser et al. 1988a; Mulligan & Katz, 1989). It is important to recognise that approximately half of these males have only minor degrees of penile artery obstruction and that their penile blood pressures can only be demonstrated to be low after lower limb exercise. This results in the 'pelvic steal' syndrome, where blood is redistributed to the buttocks and away from the partially blocked penile artery. Studies using duplex ultrasonography which would more clearly define the presence of arterial disease have been undertaken but not in older men (Robinson et al. 1989; Shabsigh et al. 1989). Morley et al. (1988) found that older men with impotence on a vascular basis and no signs of atherosclerotic disease have a 23% chance of developing a myocardial infarction or a stroke within the next 2 to 3 years compared with only a 4.5% occurrence in impotent subjects with normal penile blood pressures. Virag et al. (1984) showed that impotent subjects were more likely to have evidence of concurrent non penile atherosclerotic disease than potent men. Recently Kaiser et al. (1989) showed that males with low penile brachial pressure indices were much more likely to have abnormal electrocardiographic stress or dipyridamole thallium tests than impotent subjects with normal penile brachial pressure indices. Overall, these studies strongly suggest that arterial vascular impotence is closely correlated with atherosclerotic disease in other parts of the body. From the management perspective this means that patients with vasculogenic impotence should be carefully assessed for signs and symptoms of heart disease, peripheral vascular disease and carotid bruits. Risk factors for atherosclerotic disease should also be assessed and these should be eliminated where possible. 1.2 Venous Leakage Venous leakage from the cor )ra cavernosa appears to be responsible for 14 to 54% of all cases of impotence (Porst et al. 1987; Shabsighi et al.

Table II. Drugs that may produce impotence Diuretics

Thiazides Spironolactone

Antihypertensives

Methyldopa Clonidine Reserpine ~-B~ockers

Guanethidine Verapamil Miscellaneous cardiovascular drugs

Clofibrate Gemfibrozil Digoxin

Tranquillisers

Phenothiazines Butyrophenones

Antidepressants

Tricyclic antidepressants Monoamine oxidase inhibitors Lithium

H2-Receptor antagonists

Cimetidine Ranitidine

Hormonal agents

Estrogens Cyproterone acetate Progestogens Corticosteroids Gonadotrophin-releasing hormone (GnRH) agonists and antagonists

Cytotoxic agents

Cyclophosphamide Methotrexate

Anticholinergic agents

Disopyramide Anticonvulsants

Miscellaneous drugs

Metoclopramide Baclofen Carbonic anhydrase inhibitors Nonsteroidal anti-inflammatory drugs Tobacco Alcohol Opiates

1989). This appears to be increasingly common with advancing age because of defects in the tunica albuginea which are age-related (Tudoriu 1989). Penile venous leakage may also be caused by cavernous smooth muscle dysfunction, an increase in collagen fibres in the corpus cavernosum or abnormal venous channels. Venous leakage should be suspected when an erection cannot be main-

Impotence in Elderly Men

tained following an adequate response to intracorporeal papaverine injections. Diagnosis can be further confirmed either by pharmacocavemosometry and/or cavemosography (Aboseif et al. 1989; Brookstein 1987; Rajfer et al. 1988; Stief et al. 1989). Pharmacocavernosometry involves using heparinised saline with or without papavarine or protaglandin (alprostadil) to achieve and maintain an erection; while cavernosography refers to injection of contrast material into the cavernous bodies and obtaining x-rays. Impotent males who have a normal penile brachial pulse index and fail to respond to intracorporal vasodilators most probably have venous leakage (Williams et al. 1988). It is possible that all persons with arteriogenic impotence have some degree of venous leakage. 1.3 Central Nervous System Diseases Numerous diseases of the central nervous system (CNS) have been associated with impotence. These include temporal lobe epilepsy, multiple sclerosis and cerebrovascular accidents, particularly those that involve the limbic system (Morley 1985). Similarly, damage to the spinal cord including both trauma and tumours can lead to impotence. Autonomic neuropathy has been classically associated with impotence. In addition, sensory neuropathy can lead to an inability to maintain an erection once the penis is inserted into the vagina because of a lack of sensory feedback. There are two erectile centres in the spinal cord: thoracolumbar (TI2-Ll) and sacral (S2-S4) centres. Thoracolumbar and hypogastric plexuses mediate erections due to cortical stimuli and reflex erections involve pudendal afferents and the nervi erigentes (parasympathetic fibres of S2-S4). 1.4 Endocrine Disorders 1.4.1 Diabetes Mellitus Diabetes mellitus occurs with increasing frequency in older males such that nearly 20% of men over 65 years of age will be diabetic (Morley et al. 1987b). Impotence caused by diabetes mellitus is multifactorial and can be traced to both vascular

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impotence, and autonomic and peripheral nervous system dysfunction (de Tejada et al. 1989; Jevitch et al. 1982; Kaiser & Korenman 1988; Morley et al. 1987a). Impotent diabetic males often have a prolonged bulbocavernosus reflex latency suggesting the importance of autonomic disease in diabetics (Daniels 1989). In our unpublished studies impotence occurs at an earlier age in diabetic males compared with nondiabetic males, but overall the causes of impotence seem to occur in similar proportions when impotent diabetic males are compared with nondiabetic impotent males. 1.4.2 Others Endocrine disorders are commonly associated with impotence. Hypogonadism has been reported to be present in approximately one-third of older impotent males (Kaiser et al. 1988b). It should be pointed out that while Korenman et al. (l990a) found that both impotence and hypogonadism are commonly seen in males over 50 years of age, they appear to be independent of one another. Elevated prolactin levels produce impotence (Mooradian et al. 1988). However, in an unselected series of impotent males, hyperprolactinaemia was not common (Kaiser et al. 1992; Leonard et al. 1989). Leonard et al. (1989) found elevated prolactin levels in 5.3% of 1236 impotent males, but < 10% of these had prolactinomas. Major causes of elevated prolactin levels were drugs and chronic renal failures. In almost half the patients no cause of mildly elevated prolactin levels could be found. Patients with diabetes mellitus have been reported to be more likely to have elevated prolactin levels than persons without this condition (Mooradian et al. 1985). The majority of patients with prolactinomas have hypogonadotrophic hypogonadism and their impotence will not respond to testosterone administration. Both hyper- and hypothyroidism have been reported to produce impotence (Morley 1985). The detection of thyroid disorders in older persons is often extremely difficult to ascertain clinically (Morley et al. 1983) and for this reason it is recommended that at least a thyroxine and triiodo-

Drugs & Aging 2 (4) 1992

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thyronine uptake be obtained in all impotent patients. 1.5 Systemic Disorders A number of systemic disorders produce both impotence and hypogonadism (Morley & Melmed 1979). Renal failure can produce impotence and either primary or secondary hypogonadism (Distiller et al. 1975). Renal failure also produces hyperprolactinaemia. Zinc deficiency in some patients with renal failure has been associated with impotence (Mahajan et al. 1982). Similarly the impotence associated with cirrhosis of the liver appears to be multifactorial in origin. 1.6 Psychiatric Disorders Depression is commonly associated with impotence (Morley & Kaiser 1989) and decreases nocturnal penile tumescence (Thase et al. 1988). Depression is also associated with decreased testosterone levels (Yesavage et al. 1985). Patients with depression often have increased activity of the hypothalamic-pituitary-adrenal axis and elevated levels of corticotrophin-releasing factor (CRF) in their cerebrospinal fluid (Nemeroff et al. 1989). Animal studies have demonstrated that CRF can inhibit the ability of gonadotrophin-releasing hormone (GnRH) to release luteinising hormone (LH) from the pituitary, and thus can lead to decreased testosterone levels (Ono et al. 1984). The diagnosis of depression is often missed in older persons (Fitten et al. 1989) and, therefore, should be screened for in all older persons with impotence, utilising the Yesavage geriatric depression scale (Yesavage et al. 1983). Psychological causes are the primary cause of impotence in approximately 10% of all impotent males over the age of 50 years (Slag et al. 1983). A specific age-related cause of psychogenic impotence is the Widower's syndrome. In this condition a recently bereaved male is courted by a woman who performs many useful tasks for him. However, ifhe is not yet ready to indulge in intercourse with a new partner he may develop impotence to

protect him from this possibility, while still allowing him to receive the benefits of his new relationship (Lo Piccolo 1991). Performance anxiety, i.e. the inability to obtain an adequate erection related to anxiety concerning a previous failure, is common in many persons with early organic impotence. 1. 7 Nutritional Disorders Protein energy malnutrition is very common in older persons (Morley & Silver 1988). Protein energy malnutrition leads to hypogonadism and impotence in younger males (Morley & Melmed 1979) and also in older males. Zinc deficiency, which has been associated with diuretic use, cirrhosis of the liver, diabetes mellitus and poor nutritional intake (Morley et al. 1988c Kinlow et al. .1983), has been shown to cause impotence and hypogonadism in some subjects (Billington et aL 1990a). 1.8 Diseases of the Penis Diseases of the penis can cause impotence. In men with Peyronie's disease, fibrous bands in the penis can result in a painful deformed erection. 1.9 Drug-Induced Impotence Medications playa role in up to one-quarter of all cases of impotence in older persons (Slag et al. 1983). 16 of the top 200 prescription medications in the US may cause impotence (Soyka & Matteson 1981). Table II lists the drugs commonly associated with impotence. It should be recognised that in many cases these drugs have been implicated only in individual case reports of impotence, and as such the validity of the association should be questioned. Thiazide diuretics appear to be the most common cause of impotence worldwide because of their wide usage. Erectile dysfunction has been reported in 16.2% of bendroflumethiazide vs 8.9% of placebo recipients (Medical Research Council 1981). Impotence was the most frequent cause of withdrawal from thiazides in this study. Chlorthalidone

Impotence in Elderly Men

and hydrochlorothiazide have also been reported to cause impotence (Slag et al. 1983; Stressman & Bren-Ishay 1980). The mechanism(s) by which thiazide diuretics produce impotence is uncertain but 2 possibilities have been suggested. One is that thiazide diuretics may lower blood pressure sufficiently, such that pressures fall below the critical level necessary to maintain sufficient blood flow for a penile erection in an atherosclerotic penile artery (Morley 1985). Thiazide diuretics have also been demonstrated to cause hyperzincuria (Morley 1986). Diuretic usage is associated with decreased testosterone levels (Kaiser et al. 1988a), as is hyperzincuria (Billington et al. 1983). Zinc therapy may restore potency (see section 3.7). Spironolactone, which acts as an antiandrogen, may cause impotence (Horowitz & Gobel 1979). It can also decrease libido and cause gynaecomastia. Many antihypertensive agents produce impotence. Methyldopa produces impotence in 20 to 30% of treated patients (Reichgott 1979). Both reserpine and methyldopa increase prolactin levels and this may playa role in their ability to produce impotence (Bansal 1988). Centrally acting sympatholytics such as clonidine and reserpine (Wein & Van Arsdalen 1988) and the peripheral sympatholytic, guanethidine (Seagraves et al. 1985), have also been associated with impotence. Propranolol has been reported to produce impotence in approximately 14 to 20% of men taking it (Bissada & Finkbeiner 1988). Propranalol has also been associated with the development of Peyronie's disease (Deamer & Thompson, 1991). More selective (j-blockers such as atenolol, pindolol, metoprolol and labetalol have also been associated with impotence but less commonly than propranolol (Wein & Van Arsdalen, 1988), and topical timolol eye drops may also produce impotence. When a patient develops impotence on propranolol it is always worth trying to switch him to a more selective (j-blocker. Vasodilatory agents, angiotensin converting enzyme (ACE) inhibitors and calcium channel antagonists are less likely to produce impotence. However, we have seen impotence develop with all these agents when blood pressure is lowered below what

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appears to be critical level for maintenance of penile blood flow during an erection. No specific level can be specified as it varies from patient to patient. For example, verapamil has been shown to produce impotence and depression (Fogelman 1988). Phenothiazines and butyrophenones elevate prolactin levels and have been associated with impotence (Morley et al. 1985). Both tricyclic antidepressants and monoamine oxidase inhibitors have been associated with erectile failure (Wein & Van Arsdalen 1988). Trazodone, a heterocyclic antidepressant, can produce priapism (Deamer & Thompson 1991). Desipramine and amfebutamone (bupropion) appear to be the antidepressants least likely to produce impotence {Seagraves 1988). Lithium has also produced erectile dysfunction, but only in a small number of patients (Blay et aI. 1982; Vinarova et al. 1972). The H2-receptor antagonist cimetidine acts as an antiandrogen and is a well recognized cause of impotence (Peden et al. 1979). Other H2-receptor antagonists are less likely to cause impotence. Clofibrate produces impotence possibly by altering testosterone metabolism (Coronary Drug Project Research Group 1975), and gemfibrozil has been associated with impotence (Bain et al. 1990; Pizarro et al. 1990). Digoxin produces impotence and gynaecomastia and has been associated with an increase in plasma estrogen levels (Neri et al. 1980). The effects of digoxin may be secondary to its structural similarity to estrogens. Drugs that decrease testosterone levels will lead to a decreased libido and, in some cases, impotence. These include estrogens, GnRH agonists and antagonists, corticosteroids, ketoconazole, progestogens and cyproterone acetate (Wein & Van Arsdalen 1988). Cytotoxic agents are well recognised causes of impotence. Methotrexate used to treat patients with rheumatoid arthritis has also been associated with impotence (Blackburn & Alarcon 1989). Carbonic anhydrase inhibitor therapy for glaucoma (Epstein et al. 1987) and prostaglandin inhibition with nonsteroidal anti-inflammatory agents (Miller et al. 1989) may lead to impotence. Cigarette smoking is associated with an in-

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creased prevalence of impotence and a decreased penile brachial pressure index (Padma-Norton et al. 1986). Nicotine infusion into dogs results in inhibition of cavemosal nerve stimulation-induced erections (Jeuneman et al. 1987). Smoking 2 cigarettes is sufficient to inhibit penile erections induced by an intracorporeal injection of a low dose of papaverine (Glina et al. 1988). Thus, tobacco smoking appears to be a potent cause of impotence. Shakespeare pointed out that alcohol provokes desire but takes away performance. This remains as true today as it was in Elizabethan England. Alcohol produces a direct toxic effect on the testes with a decrease in circulating testosterone and an elevation of LH levels (Morley & Melmed 1979). In addition, alcohol can produce both an autonomic and sensory peripheral neuropathy that may playa role in the pathogenesis of impotence (Morley 1985). Alcoholism can have its onset for the first time in older persons and may be very difficult to detect. Opiate agonists produce impotence (Willenbring et al. 1989) and hypogonadism by a direct inhibitory effect on the hypothalamic-pituitary axis (Morley 1981), and also by causing hyperprolactinaemia (Willenbring et al. 1989). However, opiate addiction is rare in older persons. When pursuing the long list of medications associated with impotence it must be remembered that impotence is a common condition in older males, who are more likely to be on medications. This increases the chances of non-cause-effect associations. In most cases the effects of drugs on potency have not been truly proven and much research remains to be done to fully understand the inter-relationship between medications and impotence.

impotence. The vast majority ofhypogonadal males (as defined by a low bioavailable testosterone level) had secondary hypogonadism, i.e. an inappropriately low LH level. Older males have a diminished LH response to GnRH (Korenman et al. 1990a). Overall it appears that aging is associated with a failure at both the testicular and pituitary level of the hypothalamic-pituitary-testicular axis (Morley 1991). In addition, alterations in pulse frequency and amplitude of LH release with advancing age suggest a defect at the hypothalamic level (Kaiser et al. 1988b). Billington et al. (1990b) have shown that older impotent males with secondary hypogonadism can have their testosterone levels restored to normal by administration of the longacting opioid antagonist, nalmefene. This suggests an excess of hypothalamic {j-endorphin tone may be responsible for the secondary hypogonadism seen in some older impotent males. Vermeulen et al. (1989), on the other hand, have found that a group of older males fail to have the expected LH rise after the administration of the short-acting alterations in different opioid receptor subtypes seen with advancing age (Morley et al. 1990). Hypogonadism is clearly related to a decreased libido (Morley et al. 1991). Of interest in this regard is that only about one-third of males attending an impotence clinic have decreased testosterone levels compared with 50% of healthy males, suggesting that males with low testosterone levels may not seek treatment for impotence as often as those with normal testosterone levels (Kaiser et al. 1988a; Korenman et al. 1990a). The relationship of hypogonadism to impotence: is less clear. Davidson et al. (1979) have ShOWIl that in males with primary hypogonadism, testo· Table III. Similarities between aging and hypogonadism in male!

2. Hypogonadism, Libido, Potency and Aging Hypogonadism occurs in up to 50% of healthy males over the age of 50 years (Korenman et al. 1990a). However, in this study hypogonadism occurred equally as often in males with or without

Decreased libido Impotence Decreased muscular strength Fatigue Decreased haematocrit Decreased appetite Osteopenia

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Impotence in Elderly Men

Table IV. Side effects of testosterone therapy Prostate enlargement Possibly increased rate of prostatic cancer growth Increased haematocrit Cerebrovascular accidents Sodium retention leading to worsening of hypertension and/or heart failure Gynaecomastia due to aromatisation of testosterone to estradiol Hyperlipidaemia Liver dysfunction

sterone injections increase not only sexual thoughts but also penile erections. Billington et al. (l983b) reported that testosterone injections to middle-aged males with borderline testosterone levels improved nocturnal penile tumescence and ability to have intercourse in 45% of subjects. However, our long term experience suggests that improvements in potency are often short lived (less than 6 months) in many, but not all subjects. Clearly a subgroup of males will have their potency improved by testosterone therapy. Many ofthe changes seen with aging are similar to those associated with hypogonadism (Mooradian et al. 1988) [table III]. Little information is available on the effects of testosterone therapy on the nonsexual parameters. Hartnell et al. (1990) found that testosterone treatment for 3 months to 3 years in older males with low bioavailable testosterone levels resulted in increased sexual interests and energy, better sleep and less depression. Prostate enlargement occurred less commonly in the treated versus the untreated group. Testosterone treatment resulted in increased haemotocrit which led to a stroke in I patient. Testosterone treatment did not alter cholesterol levels, and myocardial infarction and the number of hospitalisations was not increased in the testosterone treatment group. In addition, testosterone therapy has been found to enhance muscle strength in normal males (Griggs et al. 1989). Clearly further studies on these effects of testosterone are needed before recommendations can be made on its utility. In hypogonadal subjects receiving testosterone, care must be taken to avoid and/or to screen for

side effects (table IV). Testosterone must be avoided in persons with large symptomatic prostatic hypertrophyand in patients with prostatic cancer. All persons receiving testosterone must be periodically screened with haemotocrit, prostate specific antigen and digital prostate examinations.

3. Management 0/ Impotence The modalities available for the management of impotence are listed in table V. 3.1 Mechanical Devices 3.1.1 Vacuum Tumescence Devices The availability of vacuum tumescence (external negative pressure) devices has changed the management of the older impotent male. There are 2 types of device. The more commonly used device consists of a clear plastic cylinder that is placed over the penis, and is connected to a hand-operated suction pump. The creation of a negative pressure results in blood being drawn into the corpora cavernosa and the development of an erection which can then be maintained by slipping a rubber Table V. Treatment modalities available for the management of impotence Mechanical devices

vacuum tumescence devices: removable oondom-type

Drug therapy

intracavernosal injections pentoxifylline transdermal nitroglycerin yohimbine oral phentolamine isoxsuprine zinc testosterone bromocriptine opioid antagonists

Surgery

arterial revascularjsation venous leakage ligation

Psychological treatments

management of depression management of performance anxiety management of specific conditions, e.g. Widower's syndrome

Drugs & Aging 2 (4) 1992

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ring over the base of the penis. Examples of this type of device are the ErecAid System®, the Response System® and the VED® (Vacuum Erection Device). The second type is the Synergist Erection System® that consists of a preformed silicone rubber condom that slips over the lubricated penis. Air is removed from the device by a syringe or mouth suction resulting in some penile erection. The tubing is wrapped around the penile base to maintain the erection. The penis remains in the cylinder during intercourse. All patients should be warned to remove the rubber band on the Synergist device within 30 minutes to prevent possible complications such as circular lacerations of penile skin and clotting of blood in the penis. The mechanism(s) by which negative pressure devices produce erections are unclear but appear to include partial arterial obstruction as shown by decreased penile skin temperature (Nadig et al. 1986), and a reduction in the pulse volume amplitude on pneumoplethysmography (Marmar et al. 1988). Venous obstruction also occurs as shown by the cyanotic color of the penis and superficial penile vein distension. These devices produce a high satisfaction rate (Korenman et al. 1990b; Sidi et al. 1990; Witherington 1989) and are effective in persons who have had a penile prosthesis removed (Morley et al. 1991; Moul & McLeod, 1989). In our study, we found a high satisfaction rate and most of the couples continued to use the device over 6 months, although with a diminishing frequency over time (Korenman et al. 1990b). Repeated use leads to an increase in penile brachial pressure index. We feel these devices are especially useful for couples with a well-bonded relationship and are much less suitable for those who are seeking a relationship or who have marital problems. Side effects include premature loss of penile rigidity, failure to ejaculate, pain or discomfort, inconvenience of use and occasional bruising. The Synergist device may be best used in patients with early Peyronie's disease (Mulligan & Katz 1991). However, penile sensitivity is diminished, although a high level of satisfaction has been reported in patients with spinal cord injury (Kasler & Katz 1989). It appears to be less appropriate for

general use than the pure negative pressure devices.

3.1.2 Penile Prostheses

Penile prostheses still remain the gold standard for the treatment of impotence in the US. For the sexually active male who does not want the hassles associated with other forms of management and who does not mind a relatively simple surgical procedure, it is the treatment of choice. Satisfaction, regardless of the type of prosthesis, is around 80%, provided the patient receives adequate prior counselling (Lange et al. 1984). Complications include infection and erosion of the prosthesis through the skin. There are 2 types of penile prosthesis, semi-rigid (or malleable) and inflatable (which can be selfcontained within the penis or may have parts in the abdomen and scrotum). Inflatable prostheses are approximately 5 times more expensive than the semi-rigid types and multicomponent inflatable devices have more complications than the semirigid types. The inflatable devices require manual dexterity, making them difficult to use by older persons with arthritis or frailty syndromes. Inflatable prostheses have a half-life of less than 5 years due to complications such as infection or device failure (Kabalin & Kessler 1988). Overall, semi-rigid prostheses appear to be the most cost-effective, practical choice for older persons with impotence who choose a penile prosthesis as their preferred management form. 3.2 Intracavernosal Injections Numerous drugs have been demonstrated to produce an erection following intracavenrosal injection (table VI). Papaverine, either alone or in combination with phentolamine, is an excellent erectogenic agent. Corporal smooth muscle relaxation produces helicine arteriole dilatation and increased arterial blood flow into the lacunar spaces, along with increased venous outflow. Papaverine is a phospho-

Impotence in Elderly Men

diesterase inhibitor that produces an increase in cyclic adenosine monophosphate (cAMP) levels leading to helicine arteriolar dilatation and corposal sinusoidal smooth-muscle relaxation (Juenemann et al. 1986). Dosages ranging from 15 to 60mg with each injection have been used. Patients can be instructed on how to self-inject papaverine at home with a high degree of success (Gridley et al. 1988; Sidi 1988; Zentgraf et al. 1988). The major side effects include bruising, pain on injection, induration, urethral bleeding and priapism; long term use may cause scarring or fibrosis. occasionally hypotensive symptoms may occur and the combination of papaverine and phentolamine has been reported to be associated with mild elevations of liver function parameters (Levine et al. 1989). When older subjects were injected 4 times every second week with papaverine, there was an improvement in the penile brachial blood pressure index (Mooradian et al. 1989). In some subjects who originally did not have clear-cut evidence of vascular impairment, there was return of spontaneous erections, which may represent a response in persons with psychogenic impotence. Intracorporal papaverine has been reported to break the performance anxiety-erectile failure cycle in persons with psychogenic impotence (Dhabuwala et al. 1990). The combination of papaverine and phentolamine appears to be superior to papaverine alone (Keogh et al. 1989). Alprostadil (prostaglandin El) injected intracorporally produces erections of similar quality to those seen with papaverine (Ishii et al. 1989; Schramek et al. 1990; Stackl et al. 1988). The major reported side effect has been burning; priapism has been reported occasionally. It has been Table VI. Drugs that produce an erection after intracorporeal

injection Papaverine Phentolamine Alprostodll (prostaglandin Ell Vasoactive intestinal peptide Trazodone hydrochloride Nitroglycerin Phenosybenzamine Verapamil

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shown that alprostadil will produce erections in some patients who failed phentolamine/papaverine treatment (Lee et al. 1989). Doses range from 10 to 40~g. Alprostadil appears to act through a different mechanism compared with papaverine and perhaps has a lower complication rate (Sarosdy et al. 1989). The doses of either papaverine or alprostadil vary with different patients and finding a successful dose level may be a matter of trial and error. Doses do not necessarily reflect psychogenic venous organic impotence. Intracavernosal injection of vasoactive intestinal peptide produces some increase in penile rigidity and diameter but not sufficient for intercourse (Roy et al. 1990). Vasoactive intestinal peptide has been reported to further enhance erections induced by papaverine and phentolamine (Kiely et al. 1989). Trazodone can also produce erections following intracorporeal injection (Azadzoi et al. 1990). 3.3 Pentoxifylline Increased membrane rigidity in red blood cells results in poorer passage of blood through arterioles. PentoxifYlline can decrease red blood cell membrane rigidity and restore potency in some individuals with early penile vascular disease (Korenman et al. 1988). 3.4 Transdermal Nitroglycerin Use of nitroglycerin (glyceryl trinitrate) paste to the penile shaft can enhance penile tumescence in response to an erotic video under laboratory conditions (Owen et al. 1989). This is caused by increased diameter and blood flow in the cavernous arteries. Our unpublished experienCll found that while an occasional male can obtain enhanced erections adequate for intercourse after application of 2 inches of nitroglycerin paste to the penile shaft, this was invariably accompanied by severe headaches. Claes and Baert (1989) reported that the application of a 10mg nitroglycerin patch to the penile shaft for 24 hours before intercourse will enhance

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the quality of erections in 21 out of 26 men. Headaches occurred in 12 men. 3.5 Yohimbine Yohimbine is an a2-adrenergic agonist derived from the bark of the yohimbine tree. A putative aphrodisiac, it was marketed originally as Afrodex® (in combination with testosterone and strychnine) and was claimed to produce an 80% improvement in a series of 10 000 impotent males (Margolis et al. 1971). Morales et al. (1987) found that yohimbine may enhance potency in some males with psychogenic impotence, but not in those with organic impotence. Susset et al. (989) studied 82 patients between 40 and 73 years of age (mean 61.2 years). They reported a positive response in 34% of subjects. Better responses were seen in those who had recent onset of impotence, normal penile brachial index, a normal cavernosogram, a testosterone level greater than 1387 nmolfL (400 JLg/L) and a normal somatic sacral reflex arc. The major side effects associated with yohimbine are minor abnormalities of liver function tests and hypertension. 3.6 Phentolamine and Isoxsuprine One poorly conducted study has suggested improvement of erectile function after oral ingestion of phentolamine 50mg (Gwinup 1988). The ,1-adrenergic agonist, isoxsuprine, has also been suggested to improve potency (Deamer & Thompson 1991). 3.7 Zinc Zinc deficiency results in low testosterone levels in both animals (Root et al. 1979) and humans (Billington et al. 1990). Zinc therapy has restored potency in subjects receiving haemodialysis who had a zinc deficiency (Antoniou et al. 1977). A preliminary study in humans found that zinc therapy in impotent males with low serum zinc levels and hyperzincuria restored potency in half of the subjects (Billington et al. 1983).

3.8 Testosterone While testosterone therapy is predominantly associated with improved libido, testosterone therapy will also enhance the quality and number of erections in some impotent males (Billington et al. 1983). Testosterone also improves nocturnal penile tumescence in some of these patients. Trans-scrotal testosterone patches produce physiological concentrations of testosterone but are expensive (Korenman et al. 1987). Oral testosterone preparations produce an unacceptable rate of liver dysfunction (Borhan-Manesh 1989) and for this reason intramuscular administration oftestosterone is the route of choice. 3.9 Bromocriptine The dopamine agonist bromocriptine lowers prolactin levels and will restore potency in some patients with prolactinomas (Morley 1986). 3.10 Opioid Antagonists The opioid antagonist naloxone increases LH and testosterone levels in normal males and females (Morley et al. 1980; Morley 1981). Billington et al. (1990) found that the long-acting opioid antagonist, nalmefene, increased LH and testosterone levels over 24 hours in middle-aged men with secondary hypogonadism and impotence. No effects of nalmefene on nocturnal penile tumescence could be demonstrated in the 24 hour period over which they were studied. 3.11 Surgery There have been a number of approaches to penile arterial revascularisation (Bennet et a1. 1986; Goldstein 1986; Virag et al. 1981). Overall this still remains an experimental procedure. Bypass grafting, angioplasty and infusion of agents to improve vascular flow have been tried. Surgical success in the treatment of venous leakage has been reported (Treiber & Gilbert 1989; Williams et al. 1988). Different techniques have

341

Impotence in Elderly Men

History

Change medication if possible

normal

I'v.~:;~~;1+-~rn~~~m~ '

__~

Vacuum tumescence device Intracavernosallnjection Penile prosthesis

Cavemosography ancl ? surgery

Fig. 1. Managing impotence in older males.

been tried and success rates vary (28 to 73%) [Yuiet et ai. 1992]. Venous ligation, retrograde venous embolisation-using sclerosing agents and/or coils have been used. Careful patient selection appears to be the key to this procedure being successful. 3.12 Psychological Therapies Treatment of depression can cure impotence. In

persons with specific psychological problems, sex therapy may be curati ve (LoPiccolo 1991). In some cases, older persons just require reassurance that their decreased sexual function is related to an ageassociated disease. Care needs to be taken not to force an organic treatment modality on a person or a couple who do not want it. Approximately half of older males with impotence do not want anything done about it (Slag et al. 1983).

342

4. A Rational Approach to the Management of Impotence An approach to the management of older males with impotence is outlined in figure 1. This approach goes from the least invasive to the most invasive. At all times the final needs and requests of the impotent male need to be taken into account. Appropriate management of impotence in an older male is an important quality of life issue.

Acknowledgements We gratefully acknowledge the secretarial assistance of Carol Mcleary and Carolyn Leach.

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Correspondence and reprints: Dr John E. Morley, St Louis University Medical Center School of Medicine, 1402 S. Grand Boulevard, Room M-238, St Louis, MO 63104, USA.

Impotence in elderly men.

Impotence is a highly prevalent condition occurring in 10 million American men over the age of 18 years. Alterations in vascular supply, hormonal chan...
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