Werner J. Reiter

Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study

OBJECTIVES In 1994, the Massachusetts Male Aging Study presented an inverse correlation of the serum levels of dehydroepiandrosterone (DHEA) and the incidence of erectile dysfunction (ED). We evaluated the efficacy of DHEA replacement in the treatment of ED in a prospective, double-blind, randomized, placebo-controlled study. METHODS The inclusion criteria included ED, normal physical and neurologic examinations, serum levels of testosterone, dihydrotestosterone, prolactin, and prostate-specific antigen (PSA) within the normal range, and a serum DHEA sulfate level below 1.5 micromol/L. Also all patients had a full erection after a pharmacologic erection test with 10O microg prostaglandin E1; pharmacocavernosography showed no visualization in corporeal venous structures. Forty patients from our impotence clinic were recruited and randomly divided into two groups of 20 patients each. Group 1 was treated with an oral dose of 50 mg DHEA and group 2 with a placebo one time a day for 6 months. The International Index of Erectile Function (IIEF), a 15-item questionnaire, was used to rate the success of this therapy. RESULTS Therapy response was defined as the ability to achieve or maintain an erection sufficient for satisfactory sexual performance according to the National Institutes of Health Consensus Development Panel on Impotence. DHEA treatment was associated with higher mean scores for all five domains of the IIEF. There was no impact of DHEA treatment on the mean serum levels of PSA, prolactin, testosterone, the mean prostate volume, and the mean postvoid residual urine volume. CONCLUSIONS Our results suggest that oral DHEA treatment may be of benefit in the treatment of ED. Although our patient data base is too small to do relevant statistical analysis, we believe that our data show a biologically obvious trend that justifies further extended studies.

Twelve-Year Experience With Two Courses of Adjuvant Single-Agent Carboplatin Therapy for Clinical Stage I Seminoma

PURPOSE During the past 30 years, radiation therapy with 28 to 30 Gy for para-aortic and ipsilateral iliac node areas was the standard adjuvant treatment for clinical stage I seminoma after orchiectomy. However, late effects of radiotherapy prompted a search for alternative adjuvant treatment approaches, including surveillance and application of carboplatin. In this retrospective analysis, we evaluated the efficacy and toxicity of two adjuvant single-agent carboplatin courses in 107 patients who were diagnosed with clinical stage I seminoma at our study centers between 1988 and 1999. PATIENTS AND METHODS All 107 patients (median age, 39 years; range, 24 to 63 years) received two postoperative adjuvant cycles of carboplatin (400 mg/m(2)). The pathologic tumor stage was pT1 in 84 patients, pT2 in 18 patients, and pT3 in five patients. Whole blood count and serum chemistry were evaluated weekly during treatment to assess hematologic and nonhematologic toxicity. RESULTS Six patients died from tumor-unrelated causes. The remaining 101 patients are currently alive and free of disease after a median follow-up of 74 months (range, 5 to 145 months). A detailed analysis of hematologic toxicity showed only World Health Organization (WHO) grade 1 leukocytopenia in 10.7% of all cycles and WHO grade 2 leukocytopenia in 2.1% of all cycles. CONCLUSION Regarding the absence of tumor recurrences in our retrospective analysis and the favorable toxicity profile with no episodes of long-term toxicity, we suggest that two adjuvant courses of single-agent carboplatin for clinical stage I seminoma patients might be equivalent to radiotherapy.

Frequency of urolithiasis in individuals seropositive for human immunodeficiency virus treated with indinavir is higher than previously assumed.

PURPOSE Indinavir was approved by the Food and Drug Administration in 1996 as a human immunodeficiency type 1 protease inhibitor to treat human immunodeficiency virus infection. Prompted by the high number of patients receiving indinavir who present with renal colic at our institution, we performed a detailed investigation of the true frequency of urolithiasis during indinavir treatment. MATERIALS AND METHODS We evaluated 105 patients with a mean age of 38.1 years who were treated with indinavir from 1996 to 1997. Before indinavir treatment was initiated all patients underwent renal ultrasonography, urinalysis, and determination of serum sodium, potassium, calcium, uric acid and creatinine. It was recommended that all patients drink 2 l of fluids daily, and all remained under continuous surveillance. RESULTS Metabolic evaluation and ultrasonography showed no abnormality in any case. A stone episode occurred in 13 men (12.4%) as renal colic during observation. Colic recurred in 1 patient after 2 and 5 months, and in 1 after 2 months. Median duration of indinavir treatment until an acute stone episode was 21.5 weeks (range 6 to 50). A total of 12 stones passed spontaneously. Three patients underwent ureteroscopic calculous removal and 1 was treated with extracorporeal shock wave lithotripsy. CONCLUSIONS Despite adequate patient information and compliance the rate of nephrolithiasis during indinavir therapy was 12.4%.

Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal hormone axis

OBJECTIVES To assess the impact of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) on the hypothalamic-pituitary hormone axis, we determined the endocrine changes after radical prostatectomy (RP) and transurethral resection of the prostate (TURP) for BPH and in a group of men with BPH followed up conservatively. METHODS Patients with PCa before RP (n = 49), those who underwent TURP for BPH (n = 51), and men with lower urinary tract symptoms for whom a wait-and-see strategy was chosen (n = 46) were included. Serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone were determined at baseline and 6 and 12 months later in all patients. RESULTS No significant endocrine changes were observed in the wait-and-see and TURP groups 6 and 12 months after baseline. In contrast, luteinizing hormone increased from 5.2 to 8.9 mIU/mL (P = 0.0004) and follicle-stimulating hormone from 5.7 to 9.3 mIU/mL (P = 0.0003) 12 months after RP. The rise of total testosterone from 3.9 to 4.4 ng/mL failed to reach statistical significance (P = 0.18). Patients with Gleason score 2 to 6 PCa had higher testosterone values (4.2 ng/mL) at baseline than did those with Gleason score 7 to 10 PCa (2.2 ng/mL, P < 0.05). Although 12 months after RP no changes in testosterone were observed in the low Gleason score group, the testosterone levels more than doubled in those with high-grade tumors. The increases in luteinizing hormone and follicle-stimulating hormone at 12 months, however, were comparable in both groups. CONCLUSIONS Our findings suggest a significant impact of PCa on the hypothalamic-pituitary axis that is more profound in high-grade cancer. Such an effect was not demonstrable for the transition zone in BPH.

Expression of Estrogen Receptors in Human Corpus Cavernosum and Male Urethra

Estrogen, largely produced in testis and adrenal gland, may play important roles in male reproduction. Most of the effects of estrogens are mediated by binding of estrogen to one or both of the two estrogen receptor (ER) subtypes α and β. Recently, they have been described in testis, prostate, and efferent ducts, mostly in rodents. The goal of this study was to prove the evidence of ERs in human corpus cavernosum and male urethra, exploring the protein expression of these receptors by immunohistochemistry. Corpus cavernosum and corpus spongiosum smooth muscle was immunoreactive for the androgen receptor (AR), ERα, and strongly for ERβ. Endothelial cells were negative for AR, sporadically positive for ERα, and positive for ERβ. Urethral epithelium showed strong nuclear expression of AR, predominantly in the basal cell layer, and nuclear expression of ERα in the intermediate cells. ERβ was highly expressed in almost all urethral nuclei and, much more weakly, in cytoplasm. Progesterone receptor (PGR) was negative in all cases and all tissues. These results represent the first report that ERα and particularly ERβ are regularly expressed in human penile tissue.

Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction

OBJECTIVES In 1994, the Massachusetts Male Aging Study presented the finding of an inverse correlation of the serum levels of dehydroepiandrosterone sulfate (DHEAS) and the incidence of erectile dysfunction (ED). Prompted by the positive results of a pilot study on the treatment of ED with dehydroepiandrosterone (DHEA), we performed a detailed investigation on the serum DHEAS levels in men with ED according to age category. METHODS Inclusion criteria included a history of ED for more than 6 months, a body mass index less than 30, and a state of good general health. Serum DHEAS concentrations were determined in 309 patients with ED and 133 healthy volunteers. All participants were carefully screened to assess medical factors known or suspected to alter endocrine function. Questions 3 and 4 of the International Index of Erectile Function were used to evaluate erectile function. RESULTS The mean serum levels of DHEAS in patients with ED were lower than in healthy volunteers until 60 years of age. The shape of the curve of the patients with ED indicated a quadratic decrease of DHEAS with age in contrast to a more linear decrease of DHEAS with age in the control group. CONCLUSIONS Our results suggest that until the age of 60 years, the mean serum level of DHEAS is lower in patients with ED than in healthy volunteers.

Sperm analysis and serum follicle-stimulating hormone levels before and after adjuvant single-agent carboplatin therapy for clinical stage i seminoma

OBJECTIVES During the past 25 years, radiotherapy has been considered the standard adjuvant treatment for clinical Stage I seminoma after orchiectomy. However, the late effects of this treatment have prompted a re-examination of the alternatives, including surveillance and adjuvant administration of carboplatin. To our knowledge, the present clinical study is the first to report the effects of two adjuvant courses of single-agent carboplatin on the pituitary-testicular axis and on sperm analysis. METHODS Twenty-two patients with clinical Stage I seminoma participated in a prospective investigation of gonadal function before and after carboplatin therapy. After orchiectomy but before chemotherapy, blood samples for determination of follicle-stimulating hormone (FSH) serum levels were obtained from all 22 patients. Seventeen patients provided a semen sample at the same time, but 5 were unable to do so. At the end of chemotherapy, all 22 patients provided repeated semen samples starting 1 year after the termination of treatment and continuing at intervals of 12 months. FSH serum levels were determined at the same time. The study period was 48 months. RESULTS Before chemotherapy, 2 patients (12%) had azoospermia, 9 (53%) had oligospermia, and 6 (35%) had normospermia. During the study period, sperm counts continued to increase in all patients. After 4 years, 7 patients (32%) had oligospermia and 15 (68%) normospermia. The mean prechemotherapy FSH level (15.5 IU/L) was increased in accordance with subnormal spermatogenesis, but a constant trend toward normalization was observed thereafter. CONCLUSIONS Our results show recovery of spermatogenesis after adjuvant single-agent carboplatin for clinical Stage I seminoma in a remarkably high percentage of patients.

The effect of hydroxyethyl starch on platelet aggregation in vitro

The effect of hydroxyethyl starch (HES) on hemostasis seems to be minimal when it is used in recommended amounts.A number of studies have investigated the effect of HES on platelet function when administered in vivo, but there has been no study investigating the effect on the isolated platelet function when administered in vitro. A photometrical method to assess platelet function in platelet-rich plasma (approximately 250 x 109 platelets/L) was used with platelet aggregation induced using either collagen, epinephrine, adenosine diphosphate, or ristocetin. We found a dose-dependent decrease of platelet aggregation in vitro with either collagen or epinephrine, but not with adenosine diphosphate or ristocetin. However, the changes of HES on platelet aggregation were detected only in doses larger than those routinely used in the clinical setting. Therefore, we conclude that the influence of HES at the recommended doses on initial platelet aggregation may not be clinically relevant. Implications: The effect of hydroxyethyl starch on platelet function and coagulation is discussed. This study showed no influence on platelets in clinically relevant doses in an in vitro model. (Anesth Analg 1998;86:1318-21)

Endocrine patterns in patients with benign and malignant prostatic diseases

The known importance of the endocrine system, particularly of steroid hormones, for development of the prostate gland and the fact that steroid hormones act as immunmodulators prompted us to compare hypophyseal, adrenal, and gonadal hormones, including cortisol, in patients with benign and malignant prostatic diseases.

The Impact of Urinary Extravasation after Radical Retropubic Prostatectomy on Urinary Incontinence and Anastomotic Strictures

Objective: The aim of this study was to determine the relevance of urinary extravasation as proven by cystogram 18 days after radical retropubic prostatectomy for the degree of postoperative urinary incontinence and the incidence of anastomotic strictures. Patients and Methods: A total of 225 patients underwent radical retropubic prostatectomy at our institution during a 30-month period, 215 of whom received a cystogram a mean 18 days following surgery. Three and 6 months after surgery these 215 patients were evaluated regarding the degree of urinary incontinence and the presence of anastomotic strictures. Results: The cystogram demonstrated a watertight anastomosis in 89% (n = 195; group I), the remaining 11% (n = 24; group II) showed urine extravasation. Groups I and II were comparable with respect to age, preoperative serum levels of prostate-specific antigen (PSA), tumor grade and pathological staging. Six months after surgery, there was no statistically significant (p > 0.05) difference between both groups regarding the degree of urinary incontinence and the presence of anastomotic strictures. Conclusions: The presence of urine extravasation 18 days after radical retropubic prostatectomy has no impact on postoperative urinary incontinence and the incidence of anastomotic strictures. Based on these data it is not indicated to leave the catheter in situ beyond that point of time.