Donald R. Bodner

SKELETAL FRACTURE ASSOCIATED WITH ANDROGEN SUPPRESSION INDUCED OSTEOPOROSIS: THE CLINICAL INCIDENCE AND RISK FACTORS FOR PATIENTS WITH PROSTATE CANCER

PURPOSE Limited information exists regarding the long-term risk of skeletal fracture in men on androgen suppression for prostate cancer. In addition, the clinical risk factors predisposing them to skeletal fracture are incompletely defined. We define the long-term risk and clinical risk factors for skeletal fracture in patients with prostate cancer on chronic androgen suppression. MATERIALS AND METHODS A total of 181 consecutive patients with prostate cancer on androgen suppression therapy were evaluated. The primary end point was skeletal fracture. Comprehensive demographic information was gathered, and univariate and multivariate analyses were performed to identify associations with skeletal fracture. RESULTS The proportion of patients who had survived fracture-free at 5 and 10 years on androgen suppression therapy was 96% and 80%, respectively. The black race (p = 0.009) and increased body mass index (p = 0.024) were identified as protective against androgen suppression associated skeletal fractures. A significant correlation was identified between the duration of androgen suppression and risk of skeletal fracture (p = 0.003). CONCLUSIONS Patients with prostate cancer treated with androgen suppression are at risk for skeletal fracture, and risk increases with the duration of therapy. Slender white men are at greatest risk. Conversely, black men and those with body mass indexes greater than normal (greater than 25 kg/m(2)) are at minimal risk despite a prolonged duration (10 years) of androgen suppression.

Side Effects of Self-Administration of Intracavernous Papaverine and Phentolamine for the Treatment of Impotence

Beginning October 1985, 111 men agreed to enter a prospective study of the side effects of low dose papaverine/phentolamine therapy. A total of 46 men dropped out, 30 during the initial phase. The percentage of men with painless nodules almost consistently doubled from one followup examination to the next: 8 per cent at 1 month, 17 per cent at 3 months, 32 per cent at 6 months and 57 per cent at 12 months. The average injection frequency of those with nodules was 2 1/2 times higher than those without nodules. Of the men 41 per cent required an increased dose of medications during followup, and 40 per cent of 50 men had at least 1 abnormality of liver function, most of these involving mild to moderate elevations of alkaline phosphatase and lactic dehydrogenase. Priapism was not encountered during self-injection but it did occur twice in 329 physician-administered injections. Careful regular monitoring of patients should continue as some patients enter the second year of treatment.

Why do so many people drop out from auto-injection therapy for impotence?

Although intracavernous injection of vasoactive substances has been shown to be a reasonable and reliable method of reversing impotence, studies assessing patient acceptance of this new technology are lacking. By prospectively following patients and willing partners over a 2-year period, this study sought to document patient utilization rates and the reasons why patients decline or discontinue injection therapy. The cumulative dropout rate was 46%, with patients being most at risk for leaving the program after evaluation or during the trial dose phase. Patients decline treatment because they are unable to accept the idea of injecting themselves or because of potential side effects. Patients discontinue treatment because of perceived lack of efficacy. Patient and programatic obstacles to utilization of self-injection therapy are analyzed.

Through the Eyes of Women: The Sexual and Psychological Responses of Women to their Partner’s Treatment with Self-Injection or External Vacuum Therapy

We prospectively delineated and contrasted the sexual, marital and psychological responses of women to their partners use of 2 treatments for erectile dysfunction: 1) self-injection of papaverine and phentolamine, and 2) vacuum tumescence therapy. The women were assessed at 5 points during a 12-month period with psychometric questionnaires and clinical interviews. Statistical analysis indicated that the women responded equally well to both treatments. They demonstrated significant increases in frequency of intercourse, sexual arousal, coital orgasm and sexual satisfaction. No significant changes were noted on the psychometric questionnaires. The women reported feeling more at ease in their relationships and characterized sex as more leisurely, relaxed and assured. Negative responses focused on the lack of spontaneity and hesitation about initiating sex. Self-injection and vacuum pump therapy restore potency in men and secondarily facilitate improved sexual function in women.

The Application of Intracavernous Injection of Vasoactive Medications for Erection in Men with Spinal Cord Injury

Obtaining and sustaining an erection that is firm enough and adequate for vaginal penetration and satisfactory completion of intercourse are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. During the last year we placed 20 spinal cord injury men (16 paraplegics and 4 quadriplegics) on self-injection of papaverine alone or with phentolamine. Of the patients 19 were able to obtain an erection adequate for penetration. The patient who did not obtain an adequate erection had anomalous penile venous drainage. Six episodes of priapism occurred in 3 patients: 1 had a surgical shunt placed elsewhere before he entered our program, and 2 were treated with aspiration of the corpora and injection of epinephrine. All 3 patients subsequently have been able to obtain satisfactory erections with use of lower doses of papaverine alone.

Treating Erectile Dysfunction with External Vacuum Devices: Impact Upon Sexual, Psychological and Marital Functioning

We evaluated prospectively the medical, sexual and psychosocial outcome of external vacuum devices in the treatment of erectile dysfunction. A total of 29 men regularly used such a device for 6 months and reported statistically significant improvements in erectile quality, frequency of intercourse attempts, frequency of orgasm and sexual satisfaction, as well as decreased psychiatric symptomatology, increased self-esteem and a trend toward improved marital satisfaction. Of the partners 18 reported improved sexual functioning, including increased frequency of orgasm, decreased masturbation and greater sexual satisfaction, with no changes in psychosocial parameters. The vacuum device was effective in producing erections in 89% of the men. Dropout, only 19% within 6 months, was primarily due to insufficient or pivoting erections and bruising. The most frequent adverse effects were blocked ejaculation and physical discomfort. Vacuum devices appear to provide a safe, effective, inexpensive, noninvasive treatment for erectile failure that enjoys high patient and partner acceptance.

Intracavernosal injection in the treatment of impotence: A prospective study of sexual, psychological, and marital functioning

This study assessed the sexual, psychosocial, and medical impact of intracavernosal injection of papaverine hydrochloride and phentolamine mesylate in the treatment of impotence. Ninety-six percent of patients initially achieved satisfactory erections with injections. Common side effects of self-injections included bruising (26%), nodule development (21%), abnormal liver function tests (7%), and pain (5%). No nodules resulted in penile bending or pain, and no patient discontinued treatment due to nodule development. Dropout rate to date was 35%. Self-injection treatment was associated with increases in erection quality, intercourse frequency, and sexual satisfaction, and decreases in masturbation frequency for patients. Partners also reported increases in intercourse frequency, coital arousal, and satisfaction. Decreases in general psychiatric symptomatology and increases in relationship satisfaction and self-esteem were apparent for patients, but not for partners.

The Development of Urologic Complications in Relationship to Bladder Pressure in Spinal Cord Injured Patients

The medical records of 88 patients followed through our spinal cord injury clinic were reviewed to determine if elevated intravesical pressures result in more urologic complications than are seen with low pressure bladders. Fifty-two of the patients were noted to have a high bladder pressure (sustained detrusor pressure greater than 40 cm water) on cystogram while 36 had low pressures. All patients had routine urine cultures, urodynamics, ultrasonography, radioisotope renal scans, and excretory urograms. Bladder management was directed at maintaining a low bladder pressure and included one or more of the following: intermittent catheterization, anticholinergics, alpha blockers, transurethral sphincterotomy, or indwelling catheters. Average follow-up was 6 years. Mild degrees of hydronephrosis were noted in seven (14 percent) of the patients with a high pressure bladder and in one (3 percent) with a low pressure bladder. Pyelonephritis was noted in two (4 percent) with high bladder pressure and two (5 percent) with low bladder pressure. Preservation of renal function occurred as the result of patient compliance with bladder management and bladder pressure. Sustained high detrusor pressure, when not corrected, leads to upper tract deterioration which was reversed by aggressive lower tract management.

Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury

OBJECTIVES To assess the efficacy of intraurethral prostaglandin E1 (alprostadil, MUSE) in treating erectile dysfunction in patients with spinal cord injury (SCI). METHODS Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction. All patients were at least 1 year after injury, and all had previously used intracavernosal injections successfully (Schrameks grade 5 erection). The intraurethral drug was administered in the office, in the presence of a physician, with monitoring of blood pressure. If effective, the patient was then able to use MUSE at home. The first 3 patients underwent gradual dose escalation starting with 125 microg, without the use of a constriction ring. Because of hypotension, the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg. The quality of the erection was compared with that achieved with intracavernosal injections using Schrameks grading. RESULTS The dose escalation (titration) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response. Transient hypotension was noted in these first 3 patients in whom the constricting band was not used. The highest dose of MUSE (1000 microg) was, therefore, used in the remaining 12 patients, with the constriction band. The quality of the erection varied and appeared to be less rigid in all patients (12 patients with grade 1 to 3; 3 patients with grade 4) than that noted with intracavernosal injection therapy (1 5 patients with grade 5). There was no incidence of priapism. The 3 patients with grade 4 erections tried the MUSE at home. All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy. CONCLUSIONS MUSE appears to be somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction. It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension. Its ultimate use depends on the patients level of satisfaction with the quality of the erection compared with intracavernosal injections.

Spinal Cord Compression Secondary to Prostate Carcinoma: Treatment and Prognosis

Of 35 patients with prostate carcinoma and suspected spinal cord compression 26 (74%) had myelograms and/or magnetic resonance imaging studies demonstrating epidural spinal cord compression. In 5 of 26 patients (19%) spinal cord compression was the first indication of prostate cancer. All patients were initially treated with radiation, steroids and androgen deprivation therapy. Three patients underwent laminectomy. Of 12 patients (100%) ambulatory at presentation 12 remained ambulatory. Of 12 patients (83%) who were paraparetic at presentation 10 were ambulatory after treatment. However, 2 of these patients subsequently had recurrent compression and became paraplegic. Overall, 7 of 26 patients (27%) had recurrent compression. Of 5 patients who either presented with paraplegia or in whom paraplegia developed secondary to recurrent spinal cord compression 4 remained paraplegic despite treatment. The average survival of these 5 patients after treatment was 3.9 months versus 18 months for the group as a whole. In ambulatory or paraparetic patients radiation, androgen deprivation therapy and steroids are effective palliative therapy. However, patients who present with paraplegia or in whom paraplegia developed secondary to recurrent compression are often not palliated by this combination therapy. Prophylactic radiation of vertebral metastases discovered concurrently with compressive metastases may be valuable in preventing paraplegia.