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Based on new evidence, we discuss the risk of central nervous side effects, mainly reduced cognition/dementia and depressive symptoms during the use of drugs for the treatment of lower urinary symptoms suggestive of benign prostatic hyperplasia. Cognitive impairments during use of muscarinic antagonists are well documented and mechanistically well understood, but their occurrence differs quantitatively between members of this drug class. The occurrence of depressive symptoms while using 5α-reductase inhibitors only became known recently but has now been observed consistently in several studies and is mechanistically plausible; it appears to occur with similar incidence when using dutasteride and finasteride. A moderate increase in new diagnoses of dementia has recently been reported from a single study upon use of tamsulosin but not other α

Combined therapy of benign prostatic syndrome (BPS) with α

Alopecia is the term used to describe hairless areas of the scalp. They can follow a specific pattern, be diffuse or circumscript. Androgenetic alopecia (AGA) follows a pattern: in men thinning of temples and vertex up to total baldness; in women thinning of the midline or parietal area.Lack of iron or cytostatic drugs cause diffuse alopecia, while in autoimmune diseases such as alopecia areata or lichen planus bizarre shapes of hairless areas are observed.For therapy, the following medications are used: topical minoxidil solution for AGA of men and women; systemic finasteride 1 mg for men with AGA; topical diphencyprone immunotherapy for alopecia areata; systemic antimycotic agents for tinea capitis; antibiotics such as clindamycin and rifampicin for folliculitis decalvans; systemic corticosteroids and isotretinoin for folliculitis et perifolliculitis capitis abscedens et suffodiens; topical corticosteroids for lichen planus and Kossard's frontal fibrosing alopecia.

This survey-based study examined which information urologists extract from prostate needle biopsy reports and what is needed for clinical management of prostate cancer patients.A questionnaire was developed to investigate several topics related to prostate cancer biopsies and four different clinical situations were explored separately, depending on whether the urologist intended a curative or palliative treatment.A total of 95 out of 282 (33 %) urologists responded to the questionnaire and returned anonymous responses. On average the participants had a professional career of 13 years (range 6 months to 38 years), 22 (23 %) urologists performed radical prostatectomy, 73 (77 %) were not surgically active, 55 (58 %) took 10-12 scores within the framework of the proposed first biopsy setting, 32 (34 %) took 6-8 scores and 6 (6 %) 12 scores. Urologists with a professional career15 years took significantly more biopsies. The primary and secondary Gleason patterns were required for only 36 (38 %) respondents to make treatment decisions. In prostate needle biopsies containing only a single focus of prostate cancer only 44 (48 %) of the respondents would request a Gleason score if not provided in the initial report. In addition to the Gleason score other information used by urologists to make treatment decisions included perineural invasion (60 %), periprostatic infiltration (57 %), extraprostatic spread (57 %) and the percentage of core involvement by cancer (13 %). Interestingly, in biopsies with multiple positive cores from separate locations 84 out of 95 urologists (88 %) used the highest Gleason grade to determine the treatment plan. The term atypical small acinar proliferation (ASAP) was uniformly considered sufficient to retake biopsies by 44 % (42/92) of urologists and only 53 % (49/92) of urologists performed rebiopsies in the case of high grade prostatic intraepithelial neoplasia (PIN).In this sample of 95 urologists there was high variability in the way clinicians used prostate needle biopsy pathology reports. The results of this survey underline that improved communication between urologists and pathologists is necessary.

Benign prostatic hyperplasia (BPH) is one of the most common urinary disorders in elderly men. The symptoms of this disease are increased prostate size, bladder outlet obstruction and lower urinary tract disorders. It influences bladder infections, bladder stone formation and increases the risk of urinary retention which can cause renal failure. It is necessary for the disease to be treated operatively. The number of conducted surgical interventions for pharmacotherapy has been significantly reduced in recent years due to increased efficacy in conservative therapy including combined treatment mostly with two groups of drugs: finasteride and alpha-blockers with different pharmacological activities. The aim of the study was to evaluate finasteride efficacy in the treatment of benign prostatic hyperplasia.The clinical trial was conducted from October 2008 to November 2009. According to the urologist's recommendation the patients took finasteride at a dose of 5 mg daily. A total of 4,315 patients participated in the clinical trial and were enrolled in 50 urological centres in Poland. The average age of the patients was 66.5 years, the youngest patient was 46 and the oldest was 91 (median 67.00 years, standard deviation SD±8.101). The use of finasteride at least for 2 weeks was the criterion for the patient to be included in the study. The medical trial lasted 12 months and consisted of 6 visits at which data relating to IPSS, QoL, intensification of urinary system symptoms, the results of the additional studies, PSA serum concentrations, the urinary tract USG with evaluation of residual urine and prostate, urine analysis with evaluation of crystalline, uroflowmetry, transrectal ultrasonography (TRUS) and biopsy were recorded. The study did not exclude the combined treatment with finasteride and alpha-adrenergic blocking drugs.Prostatocystitis was diagnosed in 30 men among the patients treated at the first visit after the digital rectal examination (DRE) trial and they qualified for antibiotic therapy. Suspicion of a tumor was diagnosed in 69 (1.59 %) patients of the study group at the first visit after the DRE trial and they qualified for biopsy of the prostate after the PSA trial and TRUS at the second visit. Therefore, 4,216 patients took part in the clinical trial. In the course of 12 months 392 patients were excuded from the study for different reasons: cardiac infarct, apoplexy, resignation without reason and change of address. According to the IPSS scale (International Prostate Symptom Score) a small intensification of symptoms was diagnosed in 676 patients (16%), in 2,830 patients (67%) moderate and in 718 patients (17 %) considerable. Prostate cancer was confirmed histopathologically in 50 (1.15%) out of 69 patients who qualified for biopsy of the prostate. In 2,677 (70%) patients taking both alpha-blocker and finasteride, the progression of disease reduced, the micturation improved considerably and the mass of adenoma of the prostate diminished by 40%. However, in 956 (25%) patients taking only finasteride or finasteride + phytotherapy the mass of adenoma of the prostate diminished by 40%, too. When the medical trial was finished, 212 patients (5.02 %) of the study group who showed intensive symptoms of BPH and the finasteride and alfa-blocker treatment proved not to be effective enough qualified for surgical therapy. A total of 3,824 out of 4,216 (90.7%) patients finished the medical trial and 3,612 (85.6 %) were willing to continue the further therapy.

The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way.

Assessment of the role of vitamins and micronutrients in the primary prevention of prostate cancer has changed dramatically in the past 10 years. Efforts to confirm the efficacy of a single substance have not yet succeeded. Therefore, such recommendations should at present no longer be given. Consideration could even be given to discussing whether additional large-scale interventional studies are expedient in this regard. There is still solid evidence that a well-balanced moderate diet, reduced consumption of milk products, and an Asian or Mediterranean diet are not only beneficial for general good health but can also prevent the development of prostate cancer. This should be the focus of further epidemiological studies. Thus, one can certainly speak of a paradigm shift in the prevention of prostate cancer. In contrast, available data on chemoprevention with 5α-reductase inhibitors is unequivocal: intake of finasteride as well as dutasteride correlates with significantly decreased evidence for prostate cancer. Converting this result into urologic practice remains the topic of extensive controversy.

The effect of 5α reductase inhibitors in prostate cancer has been extensively investigated. The studies determined that finasteride and also dutasteride reduced the risk of prostate cancer; however, particularly high-grade cancer was not reduced and may possibly even have been increased. This is appropriately reflected in the S3 guideline on prostate cancer. New data on early recognition show that after longer term observation prostate cancer-specific mortality can be more effectively reduced by screening than was initially shown by the original data from the ERSPC study. Active surveillance is becoming more important for the therapy of early prostate cancer. Other new publications have shown good results for patients who underwent surgery for high risk prostate cancer. For metastasized prostate cancer new immunotherapeutic, chemotherapeutic and hormonal options are now available or will soon be approved.

Primary aims of the medical therapy for BPH are improvement of subjective symptoms and quality of life as well as the prevention of long-term complications such as acute urinary retention and renal failure. Secondary goal is inhibition of disease progression. The medical therapy should be tailored to each patient according to the individual complaints and risk of progression. Plant extracts, alpha-blockers and 5-alpha reductase inhibitors represent the most common prescribed substances. Recent data suggest beneficial effects for the use of antimuscarinic agents and phosphodiesterase type 5 inhibitors.

The Prostate Cancer Prevention Trial (PCPT) has been the first interventional trial directly aimed at the prevention of prostate cancer. A total of 18,882 men over 55 years with a PSA serum level less than 3.0 ng/ml were randomized to receive either the 5-alpha-reductase inhibitor finasteride 5 mg/day or placebo for 7 years. Despite a 25% reduction of prostate cancers in the treatment arm the results were discussed controversially. This criticism was mainly due to the observation of significantly more high-grade cancers in the finasteride group. Meanwhile, results of extensive follow-up analyses have been published suggesting that this finding is most likely due to optimized tumor detection in smaller glands. Further work-up demonstrated that PSA diagnosis and the histopathological examination were not compromised by finasteride. Furthermore, in addition to a decrease of prostate cancer the amount of prostatic intraepithelial dysplasia (PIN) was also reduced under finasteride. Future research must now aim at defining high-risk groups specifically profiting from chemoprevention with a 5-alpha-reductase inhibitor.

Fueled by the results from recently published large interventional trials the topic of chemoprevention of prostate cancer has increasingly attracted the interest of practicing urologists. In this analysis the term"chemoprevention" comprises all agents not included in regular food intake. If possible, the results from interventional studies were considered. Today, it must be accepted as evidence-based that chemoprevention of prostate cancer by 5alpha-reductase inhibition using finasteride is possible. Furthermore, there is increasing evidence that selective estrogen receptor modulators (SERMs) may also have preventive potential. Prospective interventional trials investigating these substances are currently underway. Considering the high incidence and the fact that the diagnosis of prostate cancer has serious impact on the future life of the respective individuals further scientific evaluation of chemoprevention of prostate cancer is mandatory.

Prostate cancer has become the most frequently diagnosed male cancer next to non-melanotic skin cancer in the Western world. Preventive measures would therefore have important potential effects on the incidence and prevalence of this disease. A potential for effective prevention of prostate cancer is currently seen in dietary changes and perhaps in dietary supplementation with vitamins D and E or selenium. Pharmacological prevention seems a possibility with drugs acting on intraprostatic testosterone metabolism. Several large randomised trials are ongoing to clarify the potential for successful prostate cancer prevention.

Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, i.e., the administration of agents that inhibit one or more steps in the natural course of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe. Published studies were identified in a search of MEDLINE. Information about ongoing studies was provided by author access to protocols. A variety of chemoprevention studies have focused on the role of dietary factors, vitamins, and trace elements in prostate cancer. Some of these studies have been prospective, randomized, and double-blinded, while others have used retrospective or epidemiological approaches. Large-scale randomized studies are also evaluating the role of 5alpha-reductase inhibitors, which inhibit the conversion of testosterone to the more potent androgen dihydrotestosterone. Robust evidence is lacking for the value of chemopreventive agents in prostate cancer. Current evidence does suggest that vitamin E and selenium may have a role in prostate cancer chemoprevention. Data from two studies, one examining the type 1 5alpha-reductase selective inhibitor finasteride and the other using the dual 5a-reductase inhibitor dutasteride, will determine the benefits of androgen inhibition strategies for prostate cancer chemoprevention.

Androgenetic alopecia is the most common type of hair loss in men and women. The disorder represents a quantitative phenotype with an underlying genetic disposition. So far none of the causative genes have been identified. Under the influence of androgens there is a shortening of the anagen phase as well as a reduction of the cellular hair matrix volume in the involved scalp area. This results in the transformation of thick terminal hair follicles into thin vellus-like hair follicles. Clinically, patients present with an alopecia that follows a defined pattern (pattern baldness) and progresses continuously but in varying degrees. In advanced cases, men may develop baldness with remaining hair exclusively in the temporal and occipital regions. Women are prone to exhibit a more diffuse type of hair loss with pronounced thinning in the parietal region. Whereas the diagnosis of androgenetic alopecia is easy, its treatment is often difficult. The physician is commonly confronted with high patients' expectations regarding hair regrowth. Today, with minoxidil and finasteride, effective therapies are available which can lead to cessation of hair loss. The identification of underlying genes will make a more specific therapy easier to achieve.

Hair loss includes excessive shedding of hair (effluvium) and the alopecias, in which there is a decrease in the amount of hair. Both may occur diffusely, or in a circumscribed manner. The localization and pattern of circumscribed hair loss may give a clue to its cause. On the basis of morphologic criteria the alopecias are further classified into non-scarring and scarring types. Non-scarring alopecias (diffuse alopecia, androgenetic alopecia, alopecia areata) are essentially hair cycling disorders, while scarring alopecias result from irreversible destruction of the hair follicles with recognizable loss of follicular osita. Scalp biopsy should be an early step in the evaluation of any case of alopecia, in which scarring is suspected. Too little scalp hair is not a vital problem, but represents a major health care challenge. Only recently the psychological impact of hair loss has been appreciated by the medical community, though throughout history, too little hair has been a concern to mankind, and the object of cosmetic interest and quackery. Recent advances of the medical sciences have led to a better understanding of the underlying pathogenic processes and opened the venue to effective pharmacotherapy (minoxidil, finasteride) and technologies (autologous hair transplantation) for the treatment of the most common disorders. Together with the availability of such treatments, high technical standards for evaluating their efficacy have been developed and have become mandatory for appraisal of any hair growth promoting agent, both in clinical studies and in the individual patient.

Hair loss or hair thinning is a common complaint in clinical dermatology. Patients seeking advice for hair loss are not necessarily bald. In addition, the effects of therapy are hard to measure. Consequently, there is a need for a sensitive tool to monitor hair loss and treatment response. Such a method must be able to analyze the biological parameters of hair growth, which are: 1: hair density (n/cm(2)), 2: hair diameter (micrometer), 3: hair growth rate (mm/day) and 4: anagen/telogen ratio.We present the TrichoScan as a method which combines epiluminescence microscopy (ELM) with automatic digital image analysis for the measurement of human, and potentially animal hair, in situ. The TrichoScan is able to analyze all biological parameters of hair growth with a so called intraclass correlation of approximately 91% within the same operator and an intraclass correlation of approximately 97% for different operators.The application of the technique is demonstrated by comparison of the hair parameters in individuals without apparent hair loss with men with untreated AGA and men after treatment with finasteride (1 mg/day), and women who were treated with minoxidil. We were able to detect a significant increase in hair counts and cumulative hair thickness 3 and 6 months after treatment.The advantage of the TrichoScan is that it can be used for clinical studies to compare placebo versus treatment or to compare different hair growth promoting substances, it can be used for studying AGA or other forms of diffuse hair loss, and it can be adopted to study the effect of drugs or laser treatment on hypertrichosis or hirsutism.

5 alpha-reductase inhibitors and alpha 1-receptor blockers are the two main drug therapies used in the management of symptomatic benign prostatic hyperplasia. As alpha-reductase inhibitors and alpha 1-receptor blockers act through different mechanisms, a combination of the two agents might be promising. The potential benefits of combination therapy with selective alpha 1-receptor blockers and finasteride, a 5 alpha-reductase inhibitor, are currently being evaluated in several placebo-controlled prospective multicenter studies (VA Study, ALFIN Study, PREDICT Study, and MTOPS Study). The data from these studies available so far demonstrate a statistically significant benefit for the study groups receiving alpha 1-receptor blockers and combination therapy vs placebo and finasteride monotherapy in terms of symptom scores and peak urine flow rates. However, none of the studies yielded a statistically significant advantage of combination therapy over treatment with alpha 1-receptor blockers. These results should be interpreted with reference to the prostatic volume, which in the studies mentioned above was relatively low. From the results of all these studies, it can be concluded that in symptomatic patients with prostate volumes of up to 40-45 ml a combination of 5 alpha-reductase inhibitors with alpha 1-receptor blockers does not appear to provide any benefit. Yet, it can be assumed that in symptomatic patients with prostate volumes of more than 60 ml combination therapy may indeed prove more effective.

The genesis of benign prostate hyperplasia (BPH) depends on two factors: testicular androgen and the aging process. The most important androgen in the prostate is dihydrotestosterone (DHT). In the aging male the level of DHT in the prostate remains largely constant although the plasma level of testosterone decreases. DHT is formed by the reduction of testosterone by the enzyme 5-alpha-reductase, which has two isoenzymes. The 5-alpha-reductase type 2 is the predominant isoenzyme in genital tissue and thus also in the prostate. Finasteride is a 5-alpha-reductase inhibitor, which is applied in the treatment of BHP and male baldness. In the doses used finasteride acts mainly by inhibiting the 5-alpha-reductase type 2, thereby reducing the serum level of DHT by approximately 70% and by about 85-90% in the prostate. Indeed the effect of finasteride in BPH was proven in clinical studies. However, the circulating and intraprostatic DHT could be further reduced by a more effective dual 5-alpha-reductase inhibitor, which would be efficacious in the treatment of benign prostate hyperplasia and other DHT-related disorders.

Androgenetic alopecia (AGA) occurs in approximately 40% of men at the age of 40 and 50% at 50, respectively. Especially for young men progressive hair loss can be distressing. Therefore, understanding of these patients' concerns is important for appropriate management. Current understanding of the pathophysiology of AGA mainly focuses on androgen metabolism as it affects hair growth. As a result, pharmacologic treatment has made considerable progress through the introduction of selective 5 alpha-reductase inhibition with finasteride. In placebo-controlled clinical trials in men with AGA, treatment with oral finasteride proved to be effective. Minoxidil is the only pharmacological substance for topical application with proven efficacy. So far, other treatment modalities have no proven efficacy in clinical trials, so that their use cannot be recommended. Options for advanced AGA not amenable to pharmacologic treatment are autologous hair transplantation and hair replacement, both of which have recently also made progress in terms of cosmetic appeal.

Symptomatic benign prostatic hyperplasia (BPH), which a man has a 50% chance of developing during the course of his lifetime, should receive stage-related treatment. While Vahlensieck stage I disease requires no therapy, stages II and III are indications for medication. Established medications for the treatment of BPH in current use are alpha-blockers, finasteride, and the phytotherapeutic agents pumpkin seed (cucurbitae semen), nettle root (urticae radix), the phytosterols contained in Hypoxis rooperi, rye pollen and the fruits of saw palmetto (sabalis serrulati fructus). If the patient responds, these medicaments can be given life-long, or intermittently. The hard criterion for the rational use of drug treatment of BPH is, over the long term, the reduction in the number of prostate operations. In stage IV disease surgical measures--after prior compensation of renal function--are to the fore.

A 6-month, prospective, open, multicenter cohort study in 265 men with male pattern hair loss treated with oral finasteride 1 mg/day (Propecia) was conducted in the office of 52 Swiss dermatologists. The patient's head was placed in a stereotactic device, and Polaroid photographs were taken of the vertex and frontal areas. Endpoints used to determine treatment efficacy were patient self-assessment, investigator clinical assessment, and blinded assessment of the serial Polaroid photographs by a panel of 2 experienced dermatologists. Significant improvements were stated on the photographs by both clinical investigators and the blinded expert panel: 54% of patients showed improvement of hair growth at 6 months of treatment in the vertex region, and 48.7% in the frontal area. No progression of hair loss was found in an additional 38% (vertex) and 47% (frontal region), respectively. Clinical investigator and expert assessment yielded comparable results. Independently, patient self-assessment and investigator clinical assessment confirmed the progress. Propecia was well-tolerated, and no significant safety concerns were identified during the study. The photographic method was well accepted by the physicians. The office-based Polaroid photographic system allowed reliable assessment of change during treatment of male pattern hair loss with Propecia. The data generated in this manner corresponded to the antecedent results of the multicenter, placebo-controlled studies with oral finasteride.

A community-based interview and a questionnaire of men visiting the dermatologist for treatment of hair loss were conducted in Switzerland, to characterize the significance of scalp hair and self-perception of hair loss in Swiss men, and to evaluate current treatment of hair loss. 508 men, aged 15-74 years, regardless of the degree of hair loss, were interviewed by telephone, and 308 patient questionnaires were completed by 19 dermatologists. The questions addressed by the interview were: degree of self-rated hair loss, time invested for hair care, use or reasons for rejecting hair growing agents, relevant criteria for scalp hair, self-assessment with respect to different "hair communication types". The questionnaire analysed the causes of hair loss, prior and current treatment modalities, and follow-up at the dermatologist. Respondents rated their hair loss on a 5-point, textual scale that ranged from 'no hair loss' to 'bald areas'. 43% reported hair loss to some extent. For 42% a full head of hair was very important, especially for men under 29 years, who invested more time for hair care and had not lost hair. Of men with hair loss, 26% previously applied hair growing agents. Of men consulting the dermatologist for hair loss, 90% had androgenetic alopecia. 37% were previously treated: prior treatment was in 59% minoxidil, in 4% finasteride (Propecia), in 7% Aminexil, in 7% dietary supplements, and in 6% conducted by the hair dresser. In 79% treatment was switched to Propecia: of these, 73% adhered to the follow-up consultations at the dermatologist.

Androgenetic alopecia in men is genetically determined, but occurs only when the testosterone metabolite dihydrotestosterone (DHT) is present in normal levels. The drug, finasteride, inhibits the enzyme 5-alpha-reductase II, which is responsible for converting testosterone to DHT. One 1 mg tablet (Propecia) of finasteride daily lowers serum DHT levels by about 70%, and increases serum testosterone by 10%. The efficacy of finasteride 1 mg has been demonstrated in a randomized, double-blind, placebo-controlled clinical trial involving more than 1,500 men in whom a significant increase in hair density over a specified area of the scalp, and a significant improvement in appearance was noted. Following one year to treatment 48%, and following 2 years 66%, of the finasteride patients (placebo group 7% after both treatment periods) presented with visibly thicker hair growth. Side effects such as decreased libido, ejaculation disorders and erectile dysfunction were seen in fewer than 2% of the men in both the finasteride and placebo groups.