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Abstracts















PROSTATE ENLARGEMENT
(BENIGN PROSTATIC HYPERTROPHY)


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Table of Contents

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book Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia ( BPH): a multicentre trial in central Europe.
book Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.
book Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture.
book Efficacy and acceptability of Tadenan (R) (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia ( BPH): A multicentre trial in central Europe.
book Phytotherapy of BPH with pumpkin seeds - A multicentric clinical trial.
book Multicenter open trial for phytotherapy in benign prostate hyperplasia stage I and II. Sabal fruit and urtica reduces the residual urine and increases the urinary flow.
book Saw Palmetto, African prune and stinging nettle for Benign Prostatic Hyperplasia ( BPH).
book [Benign prostatic hyperplasia--the outcome of age-induced alteration of androgen-estrogen balance]?
book [Androgen and estrogen metabolism in human benign prostatic hyperplasia].
book Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate.
book The effect of androgen and estrogen on secretory epithelial cells and basal cells of the rat ventral prostate after long-term castration.
book Obesity and benign prostatic hyperplasia.
book Effect of obesity on prostatic hyperplasia: its relation to sex steroid levels.
book Larger prostatic adenomas in obese men with no associated increase in obstructive uropathy.
book Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia.
book Effect of postnecrotic and alcoholic hepatic cirrhosis on development of benign prostatic hyperplasia.
book Estrogen suppression as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia: evidence for its efficacy from studies with mepartricin.
book Chlormadinone acetate pellet implantation plus short-term oral administration in dogs with benign prostatic hypertrophy.
book Effects of the aromatase inhibitor testolactone on human benign prostatic hyperplasia.
book [Drug therapy of benign prostatic hyperplasia]


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Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia ( BPH): a multicentre trial in central Europe.

Breza J; Dzurny O; Borowka A; Hanus T; Petrik R; Blane G; Chadha-Boreham H
Department of Urology, University Hospital, Bratislava, Slovak Republic.
Curr Med Res Opin (England) 1998, 14 (3) p127-39

Pygeum africanum extract is available as Tadenan in many countries, including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. Men aged 50-75 years and in compliance with the selection criteria (including IPSS > or = 12, quality of life (QoL) score > or = 3, and maximum urinary flow < or = 15 ml/s) were first examined then recalled after two weeks during which no treatment was provided (washout and check of stability). If still compliant, they were entered at this point into a two-month period of treatment with Pygeum africanum extract 50 mg twice daily. There followed a further one-month period without treatment, the objective being to evaluate the persistence of any effects observed during the previous two months of Pygeum africanum administration. The primary efficacy parameter investigated was IPSS; the other efficacy parameters were QoL, nocturnal frequency, maximum urinary flow, average urinary flow, post-voiding residual volume and prostatic volume, after one and two months of Pygeum africanum treatment and one month after stopping treatment. A total of 85 patients were evenly distributed between the three centres and completed the entire study. At inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia was 2.6 times per night. The changes in subjective scores, IPSS and QoL after the two-month treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically significantly improved, but the modest improvement in post-voiding volume did not reach statistical significance. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.



Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.

Lowe FC; Dreikorn K; Borkowski A; Braeckman J; Denis L; Ferrari P; Gerber G; Levin R; Perrin P; Senge T
Department of Urology, St. Luke's-Roosevelt Hospital, New York, New York 10019, USA.
Prostate Nov 1 1998, 37 (3) p187-93

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken.

METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included.

RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH.

CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents. (32 Refs.)



Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture.

Geller J; Sionit L; Partido C; Li L; Tan X; Youngkin T; Nachtsheim D; Hoffman RM
AntiCancer, Inc., San Diego, California 92111, USA.
Prostate Feb 1 1998, 34 (2) p75-9

BACKGROUND: There is strong epidemiological evidence that prostate disease is significantly less prevalent in the Orient, where the intake of soy products is very high, than in the United States. We therefore undertook a study of the effects of genistein, a major component of soy, on growth of human-patient benign prostatic hypertrophy (BPH) and prostate cancer tissue in three-dimensional collagen gel-supported histoculture.

METHODS: Surgical specimens of human BPH and cancer were histocultured for 5 days to study the effects of genistein on growth, as measured by inhibition of 3H-thymidine incorporation per microgram protein on day 5.

RESULTS: Genistein in doses of 1.25-10 micrograms/ml decreased the growth of BPH tissue in histoculture in a dose-dependent manner, with little additional effect at higher doses. Prostate cancer tissue in histoculture was similarly inhibited by these doses of genistein.

CONCLUSIONS: Genistein decreases the growth of both BPH and prostate cancer tissue in histoculture. The data suggest that genistein has potential as a therapeutic agent for BPH and prostate cancer.



Efficacy and acceptability of Tadenan (R) (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia ( BPH): A multicentre trial in central Europe

Breza J.; Dzurny O.; Borowka A.; Hanus T.; Petrik R.; Blane G.; Chadha-Boreham H.; Autet W.
Dr. W. Autet, Medical Affairs, Groupe Fournier, 153 rue de Buzenval, 92380 Garches France
Current Medical Research and Opinion (United Kingdom), 1998, 14/3 (127-139)

Pygeum africanum extract is avialable as Tadenan (R), including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. Men aged 50-75 years and in compliance with the selection criteria (including IPSS less than or equal to 12, quality of life (QoL) score less than or equal to 3, and maximum urinary flow less than or equal to 15 ml/s) were first examined then recalled after two weeks during which no treatment was provided (washout and check of stability). If still complaint, they were entered at this point into a two-month period of treatment with Pygeum africanum extract 50 mg twice daily. There followed a further one-month period without treatment, the objective being to evaluate the persistence of any effects observed during the previous two months of Pygeum africanum administration. The primary efficacy parameter investigated was IPSS; the other efficacy parameters were QoL, nocturnal frequency, maximum urinary flow, average urinary flow, post-voiding residual volume and prostatic volume, after one and two months of Pygeum africanum treatment and one month after stopping treatment. A total of 85 patients were evenly distributed between the three centres and completed the entire study. At inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia was 2.6 times per night. The changes in subjective scores, IPSS and QoL after the two-month treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically significantly improved, but the modest improvement in post-voiding volume did not reach statistical significant. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.



Phytotherapy of BPH with pumpkin seeds - A multicentric clinical trial

Schiebel-Schlosser G.; Friederich M.
G. Schiebel-Schlosser, SmithKline Beecham GmbH and Co. KG, Hermannstrasse 7, 77815 Buhl Germany
Zeitschrift fur Phytotherapie (Germany), 1998, 19/2 (71-76)

Therapeutic use and safety of a pumpkin seed extract were tested in a multicentric clinical triol with 2,245 patients suffering from benign prostatic hyperplasia (Stage I to II according to Alken). Urinary symptoms were recorded by the International-Prostate-Symptom-Score according to the American Urological Association (I-PSS), the influence on quality of life has been recorded by a quality of life questionnaire (LQ-Index). Patients were treated for 12 weeks with 1-2 capsules per day containing 500 mg of a pumpkin seed extract (15-25:1). The I-PSS decreased by 47,4%, life quality improved by 46,1% during therapy. More than 96% of the patients had no undesired side effects under the treatment with Prosta Fink Forte (R).



Multicenter open trial for phytotherapy in benign prostate hyperplasia stage I and II. Sabal fruit and urtica reduces the residual urine and increases the urinary flow

Jenner R.; Haertel S.
Dr. R. Jenner, Urologie Abteilung, Kaiserstrasse 15, 76131 Karlsruhe Germany
Therapie und Erfolg Urologie Nephrologie (Germany), 1998, 10/1-2 (48-51)

102 patients with benign prostatic hyperplasia stage I-II (Alken) were treated with a combined preparation of Sabal fruit and Urtica root extracts (PRO 160/120, Prostagutt (R) forte) in a 12-week multicenter open trial. The primary outcome variable of the study, the maximal urinary flow rate, was increased by a statistically highly significant mean value of 4,2 ml/s at the end of therapy. Almost all secondary outcome variables showed a statistically significant improvement after 12 weeks, too. Particularly the reduction of the residual urine volume by 26,3 ml on average is clinically relevant. Moreover, a clear improvement of the subjective condition of the patients was observed. Besides its good efficacy, the investigational drug was excellently tolerated by the patients, thus confirming its therapeutic suitability in the treatment of benign prostatic hyperplasia stage I-II (Alken).



Saw Palmetto, African prune and stinging nettle for Benign Prostatic Hyperplasia ( BPH)

Awang D.V.C.
Canadian Pharmaceutical Journal (Canada), 1997, 130/9 (37-44+62)

No abstract.



[Benign prostatic hyperplasia--the outcome of age-induced alteration of androgen-estrogen balance]?

Weisser H, Krieg M
Institut fur Klinische Chemie, Transfusions- und Laboratoriumsmedizin, Berufsgenossenschaftliche Kliniken Bergmannsheil, Universitatsklinik der Ruhr-Universitat, Bochum.
Urologe A 1997 Jan;36(1):3-9

Although human benign prostatic hyperplasia (BPH) is the most common tumor in men, its etiology is still unclear. At present, it is only widely accepted that BPH is under the endocrine control of the testes and strongly associated with aging. Therefore, in the human prostate we describe the impact of aging on the activity of various androgen metabolizing enzymes as well as on the endogenous androgen and estrogen levels. Moreover, the inhibition of 5 alpha-reductase by finasteride (Proscar) will be reported. Among all androgen metabolizing enzymes, within the human prostate 5 alpha-reductase is the most powerful one. Most of the androgen metabolizing enzymes undergo a significant age-dependent alteration. For distinct enzymes, the correlation with age is either negative (e.g. 5 alpha-reductase), or positive. Despite a complex pattern of age-dependent alterations, the dominance of 5 alpha-reductase among all androgen metabolizing enzymes is always maintained. This is underlined by a strong accordance between the age-dependent 5 alpha-reductase activity and the corresponding age-dependent endogenous DHT level. In epithelium, both the 5 alpha-reductase activity and the DHT level decrease with age, whereas in stroma not only the 5 alpha-reductase activity is rather constant over the whole age range but the DHT level as well. In contrast to the relatively unaltered DHT content in the stroma of the human prostate, the estrogen content follows an age-dependent increase. On the other side, in epithelium such a positive correlation between the estrogen level and age is not found. Thus, the age-dependent decrease of the DHT accumulation in epithelium and the concomitant increase of the estrogen accumulation in stroma will lead to a tremendous increase with age of the estrogen/androgen ratio in the human prostate. This could be of pathogenetic importance for BPH development if in fact a balanced androgen/estrogen synergism is necessary for the integrity of the normal human prostate. Finally, it is remarkable that the inhibition of 5 alpha-reductase activity by finasteride (Proscar) is significantly stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.



[Androgen and estrogen metabolism in human benign prostatic hyperplasia].

Krieg M, Weisser H, Tunn S
BG-Kliniken Bergmannsheil-Universitatsklinik-Institut fur Klinische Chemie und Laboratoriumsmedizin, Bochum.
Verh Dtsch Ges Pathol 1993;77:19-24

Among all androgen metabolizing enzymes within the human prostate 5 alpha-reductase is the most powerful one. In the epithelium its activity decreases with age, while in the stroma it remains constant over the whole age range. Thus, in older prostates with benign hyperplasia the activity of 5 alpha-reductase is almost the same in both compartments. The same holds true for the DHT content, being highest in the epithelium of prostates from young men. With age it decreases to levels similar to those in the stroma. In contrast to DHT, estrogens are increasingly accumulated in the stroma with advancing age, while in the epithelium the estrogen level remains constant over the whole age range. The age-dependent decrease of the DHT level in the epithelium and the increase of the estrogen level in the stroma lead to a significant increase of the estrogen/androgen ratio. This could be of pathobiological importance for BPH development.



Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate.

Krieg M, Nass R, Tunn S
Institute of Clinical Chemistry and Laboratory Medicine, University Clinic Bergmannsheil, Bochum, Germany.
J Clin Endocrinol Metab 1993 Aug;77(2):375-81

It is widely believed that benign prostatic hyperplasia (BPH) is associated with aging. Thus, the question arises whether or not a correlation exists between the well known prostatic androgen and estrogen accumulation and aging. To address this question, we measured 5 alpha-dihydrotestosterone (DHT), testosterone, estradiol, and estrone in epithelium and stroma of six normal (NPR) and 19 BPH and correlated the values with the age of the donors (26-87 yr). The mean DHT level in NPR epithelium was significantly higher than in NPR stroma, and also significantly higher than in epithelium and stroma of BPH. The epithelial DHT level of NPR and BPH decreased with age, the correlation being statistically significant. The stromal DHT level of NPR and BPH showed no correlation with age. Concerning testosterone, generally rather low values were found which showed no correlation with age. The mean levels of estradiol and estrone were significantly higher in BPH stroma as compared to BPH epithelium as well as to NPR epithelium and stroma. In NPR, the mean levels of estradiol and estrone were significantly higher in epithelium than stroma. In NPR and BPH, the stromal estradiol and estrone levels increased significantly with age. In epithelium such a correlation between the estrogen levels and age was not found. Our results indicate that the prostatic accumulation of DHT, estradiol, and estrone is in part intimately correlated with aging, leading with increasing age to a dramatic increase of the estrogen/androgen ratio particularly in stroma of BPH.



The effect of androgen and estrogen on secretory epithelial cells and basal cells of the rat ventral prostate after long-term castration.

Kawamura H, Kimura M, Ichihara I
Department of Anatomy, Aichi Medical University, Japan.
Anat Anz 1993 Dec;175(6):569-75

After long-term castration, rats were injected with cotton seed oil, testosterone- and estradiol-17 beta-cypionate (CS, TC and EC). The height of the epithelial cells of the ventral prostates from the castrated rats increased after TC and EC-injection. The secretory and basal cells formed two layers of epithelium, an inner layer near the lumen with pale nuclei and another layer with dark nuclei. These two layers could result from a reduction of secretory epithelial cells. Castration decreased the ratio of secretory cells to basal cells (S/B). TC-injection increased the ratio of S/B because of the secretory epithelial cell growth. Longer dark cells may be transient cells, appearing during the differentiation of basal cells into secretory epithelial cells. A sheet branching off from the basal lamina was observed. Androgen may stimulate the synthesis of the lamina, but whether it induces the synthesis or turnover of the basal lamina has not been established. EC increased the ventral prostatic weight and secretory epithelial cell height and induced the appearance of crystalline granules. Increase in S/B ratio may result from an increase in the secretory epithelial cells, but not from basal cell multiplication due to squamous metaplasia. The ratio is significantly correlated to the weight of the ventral prostate, but not to the secretory epithelial cell height. Its value could indicate the multiplication of secretory epithelial cells, differentiation of basal cells into epithelial cells, or both. It is probable that basal cells do not change in number, but control the size of the rat ventral prostate in response to the hormone level.



Obesity and benign prostatic hyperplasia.

Giovannucci E, Rimm EB, Chute CG, Kawachi I, Colditz GA, Stampfer MJ, Willett WC
Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, MA.
Am J Epidemiol 1994 Dec 1;140(11):989-1002

Abdominal obesity increases the estrogen-to-androgen ratio and may increase sympathetic nervous activity, both hypothesized to influence the development of benign prostatic hyperplasia and the severity of urinary obstructive symptoms. In 1986 and 1987, men aged 40-75 years who were participants in the Health Professionals Follow-up Study and who were without prior diagnosis of cancer or prostatectomy provided data on weight, height, and waist and hip circumferences. The men were followed for incidence of prostatectomy for benign prostatic hyperplasia up to January 1992. In addition, the frequency and severity of symptoms of urinary obstruction were assessed among respondents to a questionnaire in 1992. Among 25,892 men who provided complete information for both surgery and symptoms, 837 men had surgery for benign prostatic hyperplasia, and 2,581 of those without surgery reported frequent urinary symptoms. After adjustment for age, smoking, and body mass index, abdominal obesity was related to prostatectomy (odds ratio (OR) = 2.38, 95% confidence interval (CI) 1.42-3.99, for those with a waist circumference > or = 43 inches (109 cm) relative to those with a waist circumference < 35 inches (89 cm); p trend < 0.0001) and with frequent urinary symptoms among those without prostatectomy (OR = 2.00, 95% CI 1.47-2.72; p < 0.0001). Body mass index, hip circumference, and waist-to-hip ratio were not associated with benign prostatic hyperplasia independently of waist circumference. These results suggest that abdominal obesity in men may increase the frequency and severity of urinary obstructive symptoms and may increase the likelihood that such obese men will undergo a prostatectomy.



Effect of obesity on prostatic hyperplasia: its relation to sex steroid levels.

Soygur T, Kupeli B, Aydos k, Kupeli S, Arikan N, Muftuoglu YZ
Department of Urology, University of Ankara, School of Medicine, Turkey.
Int Urol Nephrol 1996;28(1):55-9

In 68 men with benign prostatic hyperplasia, we evaluated the association between obesity and prostatic enlargement, as well as changes in serum levels of oestradiol, testosterone, dihydroepiandrosterone and dihydroepiandrosterone sulphate. Despite the larger adenomas, no increase in the symptom score for BPH was observed with increasing obesity. Average specimen weights increased with increasingly obesity and increasing host age from 46 to 80 g. We also found the serum oestradiol level significantly elevated in obese men who were 140% or over recommended weight compared to underweight men younger than 60 years (51.3 pg/ml versus 26.8 pg/ml, p < 0.01). This pattern was present in all age groups. These results indicate that obesity is a risk factor for prostatic enlargement but not for obstruction. Also the degree of obesity appears to have a direct effect on oestradiol levels through transformation of androgens in adipose tissue to oestrogens. In conclusion, further studies to evaluate the pathogenesis, pathophysiology, natural history and symptomatology of BPH would be of great interest and should help to define better the associations that we have recognized.



Larger prostatic adenomas in obese men with no associated increase in obstructive uropathy.

Daniell HW
Department of Family Practice, University of California Medical School, Davis.
J Urol 1993 Feb;149(2):315-7

In 379 men less than age 75 years who underwent initial transurethral prostatectomy for benign prostatic hypertrophy specimen weights were compared with host ages, obesity, smoking habits and the presence of incidental cancer. Among 334 men 60 to 74 years old average specimen weights increased with increasing obesity from 20.3 to 36.6 gm. Underweight men in comparison with men at least 30% overweight demonstrated more small specimens (10 gm. or less, 24% versus 2%, p < 0.001) and fewer large specimens (50 gm. or more, 5% versus 26%, p < 0.005). This pattern was present in smokers and nonsmokers. Adenoma weights increased with increasing host age and were larger in nonsmokers of all age groups. Body habitus was similar in the prostatectomy patients and 290 office patients of similar age, suggesting no increase in obstructive uropathy among obese men despite the larger adenomas. These observations are compatible with different risk factors for the obstructing and nonobstructing components of benign prostatic enlargement.



Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia.

Hammarsten J, Hogstedt B
Urological Section, Department of Surgery, Varberg Hospital, Sweden.
Blood Press 1999;8(1):29-36

The purpose of this study was to test the hypothesis of a causal relationship between high insulin levels and the development of benign prostatic hyperplasia (BPH) and to determine the clinical, anthropometric, metabolic and insulin profile in men with fast-growing BPH compared with men with slow-growing BPH. The present study was designed as a risk factor analysis of BPH in which the estimated annual BPH growth rate was related to components of the metabolic syndrome. Two hundred and fifty patients referred to the Urological Section, Department of Surgery, Central Hospital, Varberg, Sweden, with lower urinary tract symptoms with or without manifestations of the metabolic syndrome were consecutively included. The prevalences of atherosclerotic disease manifestations, non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension were obtained. Data on blood pressure, waist and hip measurement, body height and weight were collected and body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn from fasting patients to determine insulin, total cholesterol, triglycerides, HDL and LDL cholesterol, uric acid, alanine aminotransferase (ALAT) and prostate-specific antigen (PSA). The prostate gland volume was determined using ultrasound. The median annual BPH growth rate was 1.04 ml/year. Men with fast-growing BPH had a higher prevalence of NIDDM (p = 0.023) and treated hypertension (p = 0.049). These patients were also taller (p=0.004) and more obese as measured by body weight (p<0.001), BMI (p=0.026), waist measurement (p <0.001), hip measurement (p = 0.006) and WHR (p=0.029). Moreover, they had elevated fasting plasma insulin levels (p = 0.018) and lower HDL cholesterol levels (p = 0.021) than men with slow-growing BPH. The annual BPH growth rate correlated positively with diastolic blood pressure (rs = 0.14; p = 0.009), BMI (rs = 0.24; p < 0.001) and four other expressions of obesity and fasting plasma insulin level (rs = 0.18; p = 0.008), and negatively with the HDL cholesterol level (rs = -0.22; p = 0.001). In conclusion, the data suggest that NIDDM, hypertension, tallness, obesity, high insulin and low HDL cholesterol levels constitute risk factors for the development of BPH. The results also suggest that BPH is a component of the metabolic syndrome and that BPH patients may share the same metabolic abnormality of a defective insulin-mediated glucose uptake and secondary hyperinsulinaemia, as patients with the metabolic syndrome. The findings support the hypothesis of a causal relationship between high insulin levels and the development of BPH, and give rise to a hypothesis of increased sympathetic nerve activity in men with BPH.



Effect of postnecrotic and alcoholic hepatic cirrhosis on development of benign prostatic hyperplasia.

Cetinkaya M, Cetinkaya H, Ulusoy E, Baz S, Memis A, Yasa H, Yanik B, Ozturk B, Uzunalimoglu O
Department of Urology, Ankara Numune Hospital, Turkey.
Prostate 1998 Jul 1;36(2):80-4

BACKGROUND: The object of this study was to investigate the effects of hepatic cirrhosis on the development of benign prostatic hyperplasia and consequent effects on prostatic volume, serum prostate-specific antigen (PSA), and prostatism symptoms.

METHODS: Sixty patients with postnecrotic cirrhosis and alcoholic cirrhosis at age 40 and over, and 20 voluntary subjects in the same age group with normal hepatic functions, were evaluated with prostatic volume calculation by transrectal ultrasound, symptom scoring according to American Urology Association (AUA) criteria, measurement of serum prostate-specific antigen (PSA), serum total testosterone (TT), free testosterone (FT), estradiol (E2), and calculation of E2/FT ratios, and the results were analyzed statistically by the Mann-Whitney U-test.

RESULTS: Serum FT and TT levels were significantly lower in the hepatic cirrhosis group compared to the control group (P = 0.0000 and P = 0000, respectively). Though mean serum E2 level was a little higher in cirrhotic patients compared to controls, the difference was not significant; however, the higher E2/FT ratio in the cirrhotic group was statistically significant (P = 0.27 and P = 0.0002, respectively). In the cirrhotic group, the decrease in FT and TT levels was greater, as the disease advanced. While E2 and E2/FT ratio increase, correlate with poor prognosis, no statistically significant differences were found. Mean prostatic volume, serum PSA level, and total symptom score were significantly higher in the control group, compared to the cirrhotic group (P = 0.0001, P = 0.0006, and P = 0.002, respectively). Prostatic volume decreased parallel to severity of disease in cirrhotic patients.

CONCLUSIONS: The main reason for the decrease in mean prostatic volume in cirrhotic patients compared to subjects in the same age group with normal hepatic functions was the decrease in serum FT and TT levels, and the secondary cause was the increase in E2/FT ratio, indicating estrogenic predominance



Estrogen suppression as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia: evidence for its efficacy from studies with mepartricin.

Boehm S, Nirnberger G, Ferrari P
Department of Neuropharmacology, University of Vienna, Austria
Stefan.Boehm@univie.ac.at
Wien Klin Wochenschr 1998 Dec 11;110(23):817-23

Estrogen suppression has been introduced as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia. Recent negative results obtained in placebo-controlled trials with the aromatase inhibitor atamestane raised doubts about the efficacy of estrogen reduction. However, inhibition of aromatase not only reduces estrogens but also increases androgens which promote prostatic growth. In order to reevaluate the therapeutic efficacy of estrogen suppression, we summarize clinical trials investigating the therapeutic effects of mepartricin in the treatment of uncomplicated benign prostatic hyperplasia. Mepartricin has been reported to lower the levels of circulating estrogens without causing changes in other hormones such as androgens. By applying stringent inclusion criteria, 23 studies (including 7 placebo-controlled trials, 3 post-marketing surveillance studies, and 13 open trials) published between 1982 and 1996 were selected to be included in this report. In 79.9% of 4635 patients treated with mepartricin, its therapeutic effect was rated "good" or "excellent". In 6 out of 7 placebo-controlled trials, the therapeutic efficacy of mepartricin was significantly superior to that of placebo. Comparison of these data with results obtained with alpha 1-adrenoceptor antagonists or with the 5 alpha-reductase inhibitor finasteride indicates that mepartricin is as efficient as these widely accepted medical treatments for benign prostatic hyperplasia. Since mepartricin acts selectively upon estrogens, the present results show that estrogen suppression may be considered an efficient pharmacotherapeutic strategy in the medical treatment of uncomplicated benign prostatic hyperplasia.



Chlormadinone acetate pellet implantation plus short-term oral administration in dogs with benign prostatic hypertrophy.

Kawakami E, Shimizu M, Orima H, Fujita M, Hori T, Tsutsui T
Department of Reproduction, Nippon Veterinary and Animal Science University, Tokyo, Japan.
Int J Androl 1998 Apr;21(2):67-73

Eight beagles with benign prostatic hypertrophy (BPH) were treated by subcutaneous implantation of pellets containing 10 mg/kg chlormadinone acetate (CMA), a synthetic anti-androgen, plus daily oral administration of CMA at 2 mg/kg per day for 7 days as a therapy for BPH. Prostatic and testicular size were measured and prostatic and testicular biopsies were performed by laparotomy before and after CMA treatment. Plasma levels of luteininzing hormone (LH), testosterone and oestradiol were also measured. The clinical signs of BPH, for example haematuria and dysuria, resolved within 1 week of treatment. Mean prostatic volume decreased to 56% of the pretreatment value. At 40 weeks after treatment, prostatic volume had decreased by 36%. Histological examination of the prostate 1 week after treatment revealed reduction in diameter of the alveoli and in height of the glandular epithelium. Degeneration and atrophy of the glands were marked 4-12 weeks after treatment. In the testis, the diameter of seminiferous tubules and the number of germ cells in the seminiferous tubules had decreased markedly at 12 and 24 weeks after treatment. Although plasma LH concentrations did not undergo any marked fluctuations after CMA treatment, levels of testosterone and oestradiol were lower than before treatment. The results indicate that implantation of 10 mg/kg CMA, , plus 7-day oral administration of 2 mg/kg CMA, bring about resolution of the clinical signs and marked reduction in prostatic volume within 1 week of treatment.



Effects of the aromatase inhibitor testolactone on human benign prostatic hyperplasia.

Schweikert HU, Tunn UW
Department of Internal Medicine, University of Bonn, FRG.
Steroids 1987 Jul-Sep;50(1-3):191-200

The aromatase inhibitor testolactone was used for endocrine treatment of benign prostatic hyperplasia (BPH). Thirteen patients (mean age 79 years) with complete urinary retention (BPH stage IV) without improvement after 4 weeks of bladder drainage by suprapubic catheter were treated with testolactone 100 mg, b.i.d., for 6 months. Nine men (mean age 80 years) with identical conditions who did not receive hormonal therapy served as controls. Results, treatment group: In 7 patients spontaneous micturation reoccurred after an average treatment period of 8 weeks (group A); 6 patients continued to need the catheter (group B). Prostatic volume decreased in all patients, and an average volume reduction of 26% was found in group A, whereas in group B the decrease averaged 15%. Finally, the testosterone/estradiol ratio significantly increased in all patients during treatment. Control group: Prostatic volume did not change nor did spontaneous micturation occur during the whole observation period.



[Drug therapy of benign prostatic hyperplasia]

Vahlensieck W Jr, Fabricius PG, Hell U
Fortschr Med 1996 Nov 10;114(31):407-11

PH patients with Vahlensieck stage II or III disease are suitable for drug treatment. The points of attack are reduction of testosterone, conversion of testosterone to dihydrotestosterone, conversion of testosterone to estrogen using GnRH analogues, antiandrogens and alpha reductase inhibitors or aromatose inhibitors. Furthermore a reduction in obstruction is achieved through the use of phytopharmaceuticals containing 5-lipoxygenase and cyclooxygenase inhibitors. At present, Curcurbitae pepo seeds, Urtica dioica root, Pollinis siccae extract and Sabal serrulata seed extract are approved for the treatment of prostatic diseases in Germany. The use of alpha-1-sympathicolytic treatment may reduce muscular tone in the prostate. Combination of the various modes of action may also offer an effective form of treatment.


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