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PubMed2003

Prostate cancer prevention: what do we know now and when will we know more?

Prostate cancer prevention is now one of the most aggressively investigated areas of urologic oncology, with > 30,000 men currently participating in clinical trials in the United States alone. The Prostate Cancer Prevention Trial will complete end-of-study prostate biopsies in May 2004, and the Selenium and Vitamin E Cancer Prevention Trial is rapidly reaching its accrual goal 1-2 years ahead of schedule. These 2 studies will give definitive answers regarding 3 of the most important potential preventive interventions: finasteride, vitamin E, and selenium. Many phase II and biomarker-modulation studies are also ongoing, testing a host of other interventions. It is hoped that, within a short period of time, the clinician will be provided with strategies to reduce the risk of the disease.

Antioxidants↗
PubMedDate not supplied

[Prevalence of incidental prostatic adenocarcinoma after suprapubic adenomectomy with or without previous prostatic biopsy].

OBJECTIVES: To establish the prevalence of incidental prostate cancer after transrectal ultrasound guided prostatic biopsy and subsequent suprapubic prostatic adenomectomy and to compare it with a similar group of patients who did not underwent biopsy before surgery. To evaluate treatment, outcomes, and disease progression in patients with incidental prostate cancer. METHODS: Retrospective study of 549 suprapubic adenomectomy performed between 1996-2001 (6 yr.), comparing the group of patients with biopsies before surgery vs. the group of patients without biopsies. RESULTS: 291 (53%) patients did not undergo biopsy before adenomectomy. 258 (47%) underwent biopsies. 25 incidental prostate cancers were detected, 19 (76%) in the group of no biopsy and 6 (24%) in the biopsy group. 88% pT1a and 12%pT1b. Mean Gleason score 4.5 (3-7). 84% of the patients did not receive treatment (21) ("wait and see"); 8% (2) androgen blockade; 8% (2) finasteride (2). Three patients (12%) in the group of no biopsy had disease progression. Mean follow-up was 48.1 months (22-96). No case of cancer-specific mortality was detected. CONCLUSIONS: Global prevalence of incidental prostate cancer in our series of patients undergoing suprapubic prostatic adenomectomy was 4.55%. Prevalence was higher in the group of patients without previous biopsy (3.46%) than in the biopsy group (1.09%). Tumor progression was 12% and cancer specific survival 100% after a mean follow-up of 48.1 months (22-92). Previous prostatic biopsy in patients with suspicions digital rectal examination or elevated PSA diminishes the prevalence of incidental prostate cancer. Watchful waiting may be a valid option in some cases.

Adenocarcinoma↗
PubMed2001

The "Dorian Gray Syndrome": psychodynamic need for hair growth restorers and other "fountains of youth.".

The psychic-dynamic factors underlying the hypochondriac disorder involving an obsessive preoccupation with physical attractiveness (dysmorphophobia) and the treatment possibilities for some manifestations of this syndrome have been examined. This psychosomatic illness frequently leads to the taking of finasteride, a medication that halts the balding process in cases of androgenetic alopecia or even stimulates renewed hair growth. The nosological demarcation of the disorder requires the differential diagnosis of depressive, hypochondriac and delusionary disorders. The psychodynamics involved, as deduced from 2 case studies, takes the form of an expansion of the patients' reductionist perspective, characterized by an emphasis on external types extending to a psychogenetic attitude with regression into narcissistic fixation. The authors seek eternal youth which is a "leitmotif' of the disorder, and they apply the term "Dorian Gray Syndrome" after Oscar Wilde's novel. The treatment recommended is a course of intensive psychotherapy; often the topic of "life-style medication" must be introduced before the specific narcissistic conflicts behind the current symptoms can be treated.

Adult↗
PubMed2004

Uropharmacology: current and future strategies in the treatment of erectile dysfunction and benign prostate hyperplasia.

Because of the increasing percentage of the world male population suffering from erectile dysfunction (ED) and benign prostate syndrome (BPS), there is a need for new and innovative therapeutic approaches. Pharmacotherapy is an avenue presently being followed in the treatment of both these syndromes. A profound change in the therapy of ED has been obtained through use of the selective phosphodiesterase inhibitor sildenafil. The incidence of surgical intervention in BPS has been reduced by the introduction of uroselective alpha1-receptor antagonists and the new 5alpha-reductase inhibitors (such as finasteride, dutasteride). The investigation of mechanisms in CXC chemokine expression also offers new therapeutic possibilities in these diseases.

Adrenergic alpha-Antagonists↗
PubMed1999

Internet availability of prescription pharmaceuticals to the public.

BACKGROUND: The Internet holds great but uncertain promise for increased access and cost control in health care. OBJECTIVE: To determine access to and cost of prescription pharmaceuticals over the Internet. DESIGN: An Internet search conducted during February and March 1999. SETTING: The Philadelphia region. MEASUREMENTS: Data were collected on availability and cost of medications and physician Internet visits, requirements for physician prescriptions, and geographic location of Web-based companies and consulting physicians. Costs of comparable physician visits were obtained from Medicare and managed care organizations in the Philadelphia region. Costs of medications came from five Philadelphia community pharmacies. RESULTS: Forty-six Web sites were identified. Thirty-seven sites (33 based in the United States and 4 based outside the United States) required a prescription from a personal physician or from an Internet physician consultation. Nine sites based outside of the United States did not require a prescription or physician consultation. The median cost of an Internet physician visit was $70 (range, $20 to $90), more than 15% higher than that for a general practice visit in the Philadelphia region. Quality of physician consultation, physician qualifications and specialty, and geographic location were unknown. Median price per pill of the two most commonly offered medications was 10% higher on the Internet (before shipping charges) than at Philadelphia pharmacies ($5.49 and $4.50 for sildenafil; $1.94 and $1.83 for finasteride). CONCLUSIONS: The Internet may expand patient access to health-related services but at overall increased cost. In addition, the quality of physician Internet care is uncertain, and potential for serious abuse exists. Patients can easily provide incorrect or false information to obtain medications. Furthermore, conflict of interest exists for Web-based firms because they profit from selling medications and physician consultations.

Conflict of Interest↗
PubMed1998

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

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.

Clinical Trials as Topic↗
PubMed1999

Treatment choice for benign prostatic hyperplasia: a matter of urologist preference?

PURPOSE: New treatment modalities for benign prostatic hyperplasia (BPH) have considerably altered the decision making process in daily clinical practice. Guidelines provide a framework for treatment choice but leave much room for physician personal opinions. We identified and quantified determinants of treatment choice for BPH among urologists focusing on urologist treatment preferences. MATERIALS AND METHODS: The study population consisted of 670 consecutive patients with BPH 50 years old or older newly referred to 1 of 39 urologists in a stratified sample of 13 hospitals throughout The Netherlands. Data on patient characteristics were retrieved from patient questionnaires (symptomatology, bothersomeness, sexual function), medical records (diagnostic outcomes, co-morbidity) and urologist questionnaire (initial treatment choice and main considerations for this decision). Urologist treatment preferences were inventoried using a mailed questionnaire. Polychotomous logistic regression analysis was used to study the impact of patient characteristics and urologist preferences on treatment choice. RESULTS: Among the patient characteristics maximum flow rate, residual urine and prostate volume were strongly associated with the probability of surgery and watchful waiting. However, the influence of urologist preferences on actual decisions was also significant. Adjusted for case mix the differences in low and high preferences revealed a 2.2 times greater probability of surgery. For alpha-blockers and finasteride these ratios were 1.8 and 9.4, respectively. An additional independent effect was seen for urologist extent of experience. CONCLUSIONS: The influence of urologist personal preferences on treatment choice in BPH is considerable. Given the different efficacy and side effects of the various treatments, further consensus development is needed to enhance appropriate treatment decisions and eliminate undue costs.

Aged↗
PubMed1999

Benign prostatic hyperplasia. A review of diagnostic and treatment options.

Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland caused by histologic hyperplasia that produces an inward transmission of pressure on the urethra and an increased resistance to urine flow. The dominant risk factors for the disease are age and male gender. Weak urine stream and hesitancy are the cardinal obstructive features in BPH. Other signs and symptoms include inability to terminate micturition abruptly, sensation of incomplete emptying and occasionally, urinary retention. Many men with prostate enlargement can be successfully treated with lifestyle modification and medication. But if symptoms persist, with no significant improvement after 6 months of finasteride or 2 to 3 months of an alpha-1 blocker, consider a urology consultation. Several surgical options are available.

Aged↗
PubMed1999

[Is there a rational therapy for symptomatic treatment of benign prostatic hyperplasia with phytogenic drugs? Illustrated with the example of the prostate agent from Serenoa repens (Sabal fructus)].

In summary, even when the scientific findings are subjected to a stringently critical evaluation, it must be concluded that the denigration of herbal prostate drugs to mere placebos, as occasionally occurs, is not scientifically tenable. This is especially true of the lipophilic extract of Saw Palmetto (Serenoa repens fruits) in a daily dose of 320 mg extract. All in all, far more experimental and clinical studies have been conducted with herbal prostate drugs than with "fashionable" drugs, such as alpha 1-receptor antagonists and finasteride, since with the latter only studies of recent design are available. A dogmatic evaluation of one drug group or another is certainly not in the patients' best interest. As the overview shows, both groups of substances are useful for individualized treatment of benign prostatic hyperplasia (BPH), provided that conservative pharmacological treatment of BPH is basically accepted and that the patients' quality of life is also considered. Phytomedicines have less side effects and lower costs.

5-alpha Reductase Inhibitors↗
PubMed1999

Current aspects of antiandrogen therapy in women.

Androgenic manifestations in appearance cause not only social and psychological distress for many women, but serious skin, reproductive and metabolic abnormalities as well. Antiandrogen therapy is one of the most promising therapies to treat androgenic disorders. Clinical studies with a variety of agents, including spironolactone, cyproterone acetate, flutamide and finasteride have now proven their utility in the treatment of hirsutism, acne, androgenic alopecia and ovulatory dysfuntion in hyperandrogenic women. Comparative clinical studies, especially with low-dose regimens, suggest that these agents are well tolerated and have the potential for broader clinical utility.

Androgen Antagonists↗
PubMed2000

Practice patterns of Canadian urologists in benign prostatic hyperplasia and prostate cancer. Canadian Prostate Health Council.

PURPOSE: We reviewed the practice patterns of Canadian urologists in benign prostatic hyperplasia (BPH) and prostate cancer, and assessed the changes that occurred between 1995 and 1998. MATERIALS AND METHODS: In 1995 and 1998 questionnaires were mailed to all active members of the Canadian Urological Association who practiced adult urology in Canada. Many questions were similar, allowing for the assessment of changes in practice patterns. RESULTS: A number of changes were observed between 1995 and 1998. Cystoscopy and imaging of the upper urinary tract were used less often to evaluate uncomplicated cases of BPH. However, 39% of respondents continued to perform cystoscopy routinely. Finasteride was no longer administered in men with a smaller prostate. In 1998 before radical prostatectomy 28% of respondents routinely performed a bone scan, 29% cystoscopy and 57% chest x-ray. The number believing that maximal androgen blockade is the most effective hormonal therapy decreased from 90% to 62%, while 24% reported in the 1998 survey that they frequently administered intermittent hormonal therapy. Comparison with an American study from 1995 indicated that American urologists used the American Urological Association symptom score and performed a prostate specific antigen test more frequently than Canadian urologists. However, Canadian urologists performed cystoscopy more frequently. CONCLUSIONS: These surveys provide a useful insight into the variations in clinical practice of Canadian urologists and help to determine whether changes are occurring in regard to the development of practice guidelines. They also indicate the need to develop further guidelines, and ensure that these guidelines are widely promoted and accepted by the urological community.

Adult↗
PubMed2000

Allopregnanolone synthesis in cerebellar granule cells: roles in regulation of GABA(A) receptor expression and function during progesterone treatment and withdrawal.

Rat cerebellar granule cells were cultured for 5 days with progesterone, resulting in the conversion of progesterone to allopregnanolone, a potent and efficacious modulator of gamma-aminobutyric acid (GABA) type-A receptors, as well as in decreases in the abundance of GABA(A) receptor alpha(1), alpha(3), alpha(5), and gamma(2) subunit mRNAs. These effects were accompanied by decreases in the efficacies of diazepam and the beta-carboline DMCM with regard to modulation of GABA-evoked Cl(-) currents. Withdrawal from such progesterone treatment resulted in a rapid and selective increase in the abundance of the GABA(A) alpha(4) subunit mRNA that was associated with a restoration of receptor sensitivity to the negative modulatory action of DMCM, a positive receptor response to flumazenil, and continued reduced responsiveness of receptors to diazepam. Prevention of allopregnanolone synthesis by the 5alpha-reductase inhibitor finasteride also prevented the changes in both GABA(A) receptor gene expression and receptor function elicited by progesterone treatment and withdrawal.

Animals↗
PubMedDate not supplied

Steroidogenic enzymes in skin.

The gonadal synthesis of testosterone from cholesterol involves four enzymes, namely, cytochrome P-450 side-chain cleavage enzyme, cytochrome P-450 17a-hydroxylase/lyase, 3b-hydroxysteroid dehydrogenase, and 17b-hydroxysteroid dehydrogenase. A significant part of the plasma-borne testosterone is converted in androgen target tissues, such as the skin, to the more potent androgen dihydrotestosterone by the steroid 5a-reductase type 1 and type 2 isoenzymes. Dihydrotestosterone, which binds to the nuclear androgen receptor with much greater affinity than testosterone, is the androgen responsible for a process leading to androgenetic alopecia. Consequently, the 5a-reductase inhibitor finasteride was developed and has proven efficacious in promoting hair growth as a consequence of lowering scalp and plasma dihydrotestosterone levels. In contrast to the direct synthesis of dihydrotestosterone from testosterone, biologically inactive C19-steroids produced by glandular and peripheral tissues may also feed into the scalp skin production of dihydrotestosterone by the local expression of reductive 17b-hydroxysteroid dehydrogenase, oxidative 3a-hydroxysteroid dehydrogenase, and 3b-hydroxysteroid dehydrogenase enzymes. Aberrant expression of one or more of these enzymes, could conceivably result in increased scalp dihydrotestosterone levels, and possibly, acceleration of the balding process in genetically predisposed men and women.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

Progesterone and 3alpha,5alpha-THP enhance sexual receptivity in mice.

Progesterone (P) and its metabolites' effects on sexual receptivity (lordosis) of mice was examined. P dosages that produced normal circulating concentrations of P and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) enhanced lordosis of ovariectomized, sexually experienced C57BL/6J (C57), +/+ C57BL/6Jx129SvEv (C57x129), and -/- C57BL/6Jx129SvEv (PRKO) mice. Only C57 and C57x129 mice had increases in progestin receptor (PR)-immunoreactivity (PR-IR) in the hypothalamus. RU38486, a PR antagonist, attenuated lordosis of C57 and C57x129, but not PRKO, mice; epostane, a progestin biosynthesis inhibitor, reduced plasma progestins; and finasteride, a P metabolism inhibitor, reduced plasma 3alpha,5alpha-THP and attenuated lordosis of all mice. For sexually naive mice, greater lordosis on initial sexual experience corresponded to greater concentrations of plasma and central progestins and increased central binding of a GABAA agonist, muscimol, compared with that seen in mice with lower lordosis on initial mating. Thus, P-facilitated receptivity in mice involves P and 3alpha,5alpha-THP and their actions at PRs and GABAA receptors.

5-alpha-Dihydroprogesterone↗
PubMed2000

[Measurement of T and DHT contents in normal and diseased human prostate tissues].

OBJECTIVE: To measure T and DHT contents in normal and diseased human prostate tissues. METHODS: Serum and prostatic T and DHT levels were measured in patients with normal, benign prostatic hyperplasia and prostate cancer. RESULTS: A decline was observed in serum T level, but no change in DHT concentration with aging. There were no significant differences in both blood T and DHT levels between the patients with BPH or PCA and normal controls. Serum T level remained constant. There were excessive accumulation of DHT in BPH, and cancerous prostate tissues were responsible for the pathogenesis of BPH and PCA. Finasteride treatment did not produce a reduction in prostatic DHT content. CONCLUSION: More than one form of 5a-reductases is responsible for the high level of DHT in the gland.

Adult↗
PubMed2002

Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study.

OBJECTIVE: While the lipido-sterolic extract of Serenoa repens (LSESr)-Permixon((R))-has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. METHODS: Eight hundred and eleven men with symptomatic BPH (I-PSS> or =10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4mg/day (N=354) or Permixon 320mg/day (N=350). I-PSS, QoL and Q(max) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269). RESULTS: At 12 months, I-PSS decreased by 4.4in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Q(max) was similar in both treatment groups (1.8ml/s Permixon, 1.9ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. CONCLUSION: This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.

Adrenergic alpha-Antagonists↗
PubMed2002

Managing benign prostatic hyperplasia.

Medical and surgical options for the treatment of benign prostatic hyperplasia have expanded in recent years. Saw palmetto, the most widely used complementary medication, is less effective than standard medical therapy but has fewer side effects. Although non-selective alpha blockers provide rapid relief of symptoms and are relatively inexpensive, they can cause dizziness and orthostatic hypotension. These effects occur less often with tamsulosin, a more selective alpha blocker. Finasteride, a 5alpha-reductase inhibitor, slowly reduces prostatic volume but is not as effective as alpha blockers, especially in men with a smaller prostate. Dutasteride, a new 5alpha-reductase inhibitor, has recently been labeled for the treatment of benign prostatic hyperplasia. Surgery may be appropriate initial treatment in patients with severe symptoms who are not at high risk for complications. Surgery may also be indicated in patients who have failed medical therapy or have recurrent infection, hematuria, or renal insufficiency. Transurethral resection of the prostate is effective in most patients, but it carries some risk of sexual dysfunction, incontinence, and bleeding. Surgical procedures that use thermal microwave or laser energy to reduce hyperplastic prostate tissue have recently become available. In general, the newer procedures are less expensive than transurethral resection of the prostate and have fewer complications; however, the need for retreatment is somewhat greater with these less invasive techniques.

Complementary Therapies↗
PubMed2002

[Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study].

OBJECTIVE: While the lipidosterolic extract (LSESr) of Serenoa repens--Permixon--has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. METHODS: Eight hundred and eleven men with symptomatic BPH (international prostdate symptom score, I-PSS > or = 10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4 mg per day (N = 354) or Permixon 320 mg per day (N = 350). I-PSS, QoL and maximum urinary flow rate (Qmax) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol (PP) population of 542 patients (tamsulosin: N = 273; Permixon: N = 269). RESULTS: At 12 months, I-PSS decreased by 4.4 in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Qmax was similar in both treatment groups (1.8 ml/s Permixon, 1.9 ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. CONCLUSION: This study demonstrated that Permiwon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.

Adrenergic alpha-Antagonists↗