Desenvolvimento de uma estratégia para a prospecção de fármacos inibidores da enzima esterol 24-C-metiltransferase (ERG6) de Leishmania spp / Development of a strategy for prospecting drugs inhibiting the enzyme sterol 24-C-methyltransferase (ERG6) from Leishmania spp

A leishmaniose é um grave problema de saúde pública, sendo considerada uma doença extremamente negligenciada, para a qual ainda não existe vacina licenciada para uso em humanos e o tratamento é caro e tóxico. Na busca para o desenvolvimento racional de novos fármacos, a escolha de um alvo seletivo no parasito é essencial. Enquanto os mamíferos produzem colesterol, os tripanossomatídeos produzem esteróis com esqueleto ergostano, como o ergosterol. O passo divergente da via dos parasitos é a transferência de um grupamento metila da S-adenosilmetionina (SAM) para o carbono 24 de esteróis com estrutura colestano, formando uma ramificação no C24 não existente nos esteróis de mamíferos, catalisado pela enzima esterol 24-C-metiltransferase (ERG6). Sendo assim, é proposta do presente trabalho estabelecer uma estratégia para a prospecção de fármacos inibidores da enzima ERG6 de Leishmania spp. Para esse objetivo, preparamos cepas de L. infantum e L. amazonensis que superexpressam a ERG6. A confirmação da expressão gênica aumentada em ambas cepas de Leishmania foi confirmada por PCR quantitativo (qPCR) em diferentes condições experimentais

Em seguida, essas cepas foram utilizadas para realização de triagem de fármacos. Promastigotas e amastigotas de Leishmania spp. superexpressando ou não o alvo estudado foram incubados com os diferentes compostos por 72h. Promastigotas de L. amazonensis superexpressando a ERG6 se tornaram resistentes aos azapterocarpanos LQB 333, 336, 339 e 341, e a cepa recombinante de L. infantum se tornou resistente às substâncias LQB 336, 339, 341 e 343. Em relação aos azasteroides, todos os derivados da série ND apresentaram atividade leishmanicida contra as formas promastigotas de Leishmania spp. Além disso, promastigotas e amastigotas de L. infantum que superexpressam a enzima alvo se tornaram resistentes quando tratadas com as substâncias ND-1 e ND-2. As amastigotas de L. amazonensis que superexpressam a ERG6 também se tornaram resistentes à ND-1 e ND-2. Os resultados apresentados neste trabalho indicam que o mecanismo de ação dos azapterocarpanos e os azasteroides destacados acima pode ser a inibição da ERG6. (AU)

Inhibitory effect of dutasteride on the expressions of epididymal Claudin1 and β-catenin in male rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and β-catenin in rats.</p><p><b>METHODS</b>Sixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and β-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated.</p><p><b>RESULTS</b>Dutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and β-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05).</p><p><b>CONCLUSION</b>Dutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and β-catenin expressions, and damaging epididymal epithelial cell junctions.</p>

The effectiveness of finasteride and dutasteride used for 3 years in women with androgenetic alopecia.

Background: The effectiveness of finasteride and dutasteride in women with androgenetic alopecia has been the subject of debate. Aim: To evaluate the effectiveness of finasteride and dutasteride on hair loss in women with androgenetic alopecia over a period of 3 years. Methods: From a database containing systematically retrieved data on 3500 women treated for androgenetic alopecia between 2002 and 2012 with finasteride 1.25 mg or dutasteride 0.15 mg, a random sample stratified for age and type of medication was taken to yield 30 women in two age categories: below and above 50 years, and for both medications. Hair thickness of the three thinnest hairs was measured from standardized microscopic images at three sites of the scalp at the start of the treatment and after 3 years of continuous medication intake. The macroscopic images were evaluated independently by three European dermatologists/hair experts. The diagnostic task was to identify the image displaying superior density of the hair. Results: Both age categories showed a statistically significant increase in hair thickness from baseline over the 3‑year period for finasteride and dutasteride (signed rank test, P = 0.02). Hair thickness increase was observed in 49 (81.7%) women in the finasteride group and in 50 (83.3%) women in the dutasteride group. On average, the number of post‑treatment images rated as displaying superior density was 124 (68.9%) in the finasteride group, and 118 (65.6%) in the dutasteride group. Dutasteride performed statistically significantly better than finasteride in the age category below 50 years at the central and vertex sites of the scalp. Conclusions: Finasteride 1.25 mg and dutasteride 0.15 mg given daily for 3 years effectively increased hair thickness and arrested further deterioration in women with androgenetic alopecia.

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

Objectives Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. .

Hair characteristics and androgenetic alopecia in Koreans

The scalp hair is composed of one hundred thousand of hairs. Each hair goes through the three phases of the hair cycle, which causes the hair to turn from an anagen hair into a catagen hair, then into a telogen hair, and finally into a new anagen hair. The number of hairs is maintained at a relatively constant level because each hair has its own hair cycle. The hair of Koreans is relatively thicker than that of Caucasians and Africans but its growth rate and density are lower. There are various factors that influence hair growth such as hormones, nutritional status, and drugs. However, androgen is most important among these factors and, particularly, androgenetic alopecia is caused by androgen and genetic factors. Because excessive dihydrotestosterone produced by 5alpha-reductase is of the greatest importance in androgenetic alopecia, finasteride or dutasteride, which inhibits the action of 5alpha-reductase, is effective in treating androgenetic alopecia. Also, minoxidil is widely used as it promotes hair growth. Furthermore, there are various types of hair diseases and specialized examination is required for differential diagnosis.

Impact of Treatment With Statins on Prostate-Specific Antigen and Prostate Volume in Patients With Benign Prostatic Hyperplasia

PURPOSE: We investigated the impact on prostate-specific antigen (PSA) and prostate volume (PV) of statin medication for 1 year in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We retrospectively investigated 791 patients in whom BPH was diagnosed. For analysis, the patients were divided into four groups according to their medications: group A, alpha-blocker; group B, alpha-blocker+statin; group C, alpha-blocker+dutasteride; group D, alpha-blockers+statin+dutasteride. To investigate changes in serum PSA, PV, and total cholesterol, we analyzed the data at the time of initial treatment and after 1 year of medication. RESULTS: After 1 year, group A showed a 1.3% increase in PSA and a 1.0% increase in PV. Group B showed a 4.3% decrease in PSA and a 1.8% decrease in PV. The difference in PV reduction between groups A and B was statistically significant (p<0.001). Group C showed a 49.1% reduction in PSA and a 22.9% reduction in PV. Group D showed a 51.6% reduction in PSA and a 24.5% reduction in PV. The difference in PV reduction between groups C and D was not statistically significant (p=0.762). By use of a multivariate logistic regression model, we found that the probability of PV reduction after 1 year was more than 14.8 times in statin users than in statin nonusers (95% confidence interval, 5.8% to 37.6%; p<0.001). CONCLUSIONS: Statin administration reduced PSA and PV in BPH patients. This finding may imply the improvement of lower urinary tract symptoms and prevention of cardiovascular disease and chemoprevention of prostate cancer with statin treatment.

Current Status of 5alpha-Reductase Inhibitors in Prostate Disease Management

The key enzyme in the androgen synthesis and androgen receptor pathways is 5alpha-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia.

Alopecia androgenética femenina: Parte II: tratamiento / Female androgenetic alopecia: Part II: treatment

Como en el varón, el tratamiento tópico de alopecia de patrón femenino (AF) es con minoxidil al 3 por ciento - 5 por ciento dos veces al día. También puede usarse el minoxidil combinado con α-tocoferol o con otros tratamientos tópicos que elevan localmente el factor de crecimiento vascular endotelial. Comentamos nuestra experiencia con esta asociación. Los efectos secundarios más frecuentes en mujeres son la dermatitis de contacto y la hipertricosis de cara y antebrazos. Cuando la alopecia femenina se asocia a elevados niveles de andrógenos hay que utilizar terapéutica antiandrogénica. El síndrome de persistencia de la adrenarquía (SAHA suprarrenal) y alopecia en hiperandrogenismo suprarrenal deben tratarse con supresión suprarrenal y antiandrógenos. La supresión suprarrenal la efectuamos con glucocorticoides como dexametasona, prednisona o deflazacort. La terapia antiandrogénica incluye acetato de ciproterona, drospirenona, espironolactona, flutamida y finasterida. El síndrome por exceso de eliminación de andrógenos ováricos (SAHA ovárico) y alopecia del hiperandrogenismo ovárico pueden tratarse con supresión ovárica y andriandrógenos. La supresión ovárica incluye el uso de anticonceptivos que contengan un estrógeno, etinilestradiol, y un progestágeno. El antiandrógeno acetato de ciproterona, siempre acompañado de un anticonceptivo tricíclico, es la mejor terapéutica de la alopecia femenina. Los antagonistas de las hormonas liberadoras de gonadotropinas (GnRH) como el acetato de leuprolida suprimen la función hipofisaria y gonadal mediante la reducción de los niveles de LH y FSH, y como consecuencia se reducen los niveles de esteroides ováricos, especialmente en el síndrome de los ovarios poliquísticos. El SAHA hiperprolactinémico y alopecia del hiperandrogenismo de procedencia hipofisaria deben tratarse con bromocriptina o cabergolina. Las mujeres con alopecia posmenopáusica y altos niveles séricos de andrógenos en la premenopausia...

Topical treatment of female patgten hair loss (FPHL) is with minoxidil 3 percent-5 percent twice daily. Combination of minoxidil with α-tocopherol or with other topical treatment with possibility to enhance VEGF can be used. Our experience with this association is commented. Side effect of minoxidil is contact dermatitis and hipertricosis on face and forearm. When FPHL is associated with high levels of androgens systemic antiandrogenic therapy must be used. Persistent adrenarche syndrome (adrenal SAHA) and alopecia of adrenal hiperandrogenism must be treated with adrenal suppression and antiandrogens. Adrenal suppression is achieved with glucocorticosteroids such as dexametasona, prednisone ordeflazacort. Antiandrogen therapy includes cyproterone acetate, drospirenone, spironolactone, flutamide and finasteride. Excess release of ovarian androgens (ovarian SAHA) and alopecia of ovarian hiperandrogenism must be treated with ovarian suppression and antiandrogens. Ovarian suppression includes the use of contraceptives containing an estrogen, ethinyl estradiol, and a progestogen. Antiandrogens such as cyproterone acetate, always accompanied by tricyclic contraceptives, are the best antiandrogen to use in FPHL. Gonadotropin-releasing hormone (GnRH) agonists such as leuprolide acetate suppress pituitary and gonadal function through a reduction in LH andFSH levels. Subsequently, ovarian steroids levels will also be reduced, especially in patients with polycystic ovary syndrome. SAHA with hyperprolactinemia and alopecia of hyperprolactinemic hiperandrogenism should be treated with bromocriptineor cabergoline. Postmenopausal alopecia, with previous high levels of androgens or with PSA over 0.02 ng/ml improves with 2.5 mg/day of finasteride or 0,25 mg/day of Dutasteride. Although we do not know the reason, postmenopausal alopecia in normoandrogenic women also improves, probably in relation with the doses of 2.5 mg day that received...

Comparison of Clinical Efficacy of Finasteride and Dutasteride as 5-alpha Reductase Inhibitor / 대한남성과학회지

PURPOSE: To compare the clinical therapeutic efficacy of finasteride and dutasteride as 5-alpha reductase inhibitor (5-ARI) in the medical treatment of benign prostate hyperplasia. MATERIALS AND METHODS: From July 2007 to July 2010, 354 benign prostatic hyperplasia patients with combination medication : alpha blocker plus 5-ARI were enrolled. These patients were classified into a finasteride medication group (F group) and dutasteride medication group (D group) retrospectively. We initially measured the total prostate volume (TPV), prostate specific antigen (PSA), International Prostate Symptom Score (IPSS), quality of life score (QoL), maximal flow rate (Qmax), and post-void residual urine (PVR). After at least twelve months of medication, we rechecked these clinical parameters and during medication, side effects related to medication were also recorded. RESULTS: The F group (n=129) and D group (n=225) showed no differences in baseline characteristics for age, TPV, IPSS, QoL scores, or PSA. After medication, decreases in TPV were relatively higher in the D group than the F group (28.2% vs 20.5%). In addition, the decrease in PSA (43.6% vs 39.2%) and IPSS score (4.6 vs 3.5) were also higher in the D group. There were no significant differences in QoL score, Qmax, PVR change, or side effects between the two groups. CONCLUSIONS: Dutasteride showed greater efficacy in reduction of TPV and PSA and in symptomatic improvement by IPSS score than finasteride. More large scale studies about the differences on clinical efficacy of finasteride and dutasteride are needed.

Post-marketing Surveillance of the Safety of Dutasteride Prescribed to Korean Patients with Benign Prostate Hyperplasia

BACKGROUND: Dutasteride is an inhibitor of both types I and II 5 alpha-reductase and was approved in Korea in April 2004. This post-marketing surveillance was to assess the safety of dutasteride in Korean patients with benign prostate hyperplasia in real life and to elucidate the risk factors related adverse events. METHODS: From December 2004 to January 2010, 3,977 patients were enrolled by 184 urologists. According to post-marketing surveillance regulation, patients were enrolled consecutively. Patients administered dutasteride at least once were included in safety assessment. The incidences of any adverse events and serious adverse events were evaluated. Multiple logistic regression method was used to identify risk factors related to adverse events. RESULTS: The safety assessment included 3,870 patients with the mean age of 67.3 years. The incidence of adverse events was 3.8 %. The most frequent adverse event was impotence (75 cases, 1.9 %), libido decrease (49 cases, 1.3 %), ejaculation disorder (30 cases, 0.8 %), and gynecomastia (5 cases, 0.1 %). The incidence of unexpected adverse events was 0.5 % and cerebral infarction, lung cancer, pulmonary embolism, and diarrhea were reported as serious adverse events. CONCLUSION: In this survey, impotence was the most frequently reported adverse events. Dutasteride was well tolerated in Korean patients with benign prostate hyperplasia. These results updated the safety information and would provide important additional information for prescribers.

Computerized Measurement on Angular Parameters for Hallux Valgus: Comparison of 100% and 150% Magnified Digital Radiography / 대한족부족관절학회지

PURPOSE: To study computerized measurements of angular parameters on 100% and 150% resized digital radiography of hallux valgus deformity. MATERIALS AND METHODS: 30 digital radiography of standing foot anteroposterior view of hallux valgus patients were included. Two observers(A, B) independently measured hallux valgus angle (HVA), 1-2 intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) in two times on both 100%-size and 150% magnified images respectively, using computerized measurement software tools. The results were interpreted with the statistical software program, Statistical Analysis System, version 9.2. RESULTS: In repeated measurements of each observer, measurements on 150% magnified image showed no differences of all three parameters and with 100%-size image, there were differences of HVA (observer A) and 1-2 IMA (observer B) (p>0.05). When testing interobserver reliability, both observers showed differences in measurement of HVA and DMAA (p<0.05), but no differences in measurement of 1-2 IMA in both images. Within the 95% confidence interval, limits of error of measurements between two observers on HVA, IMA and DMAA were 2.7degrees 1.4degrees and 5.0degrees respectively in 100%-size images, and 2.6degrees, 1.6degrees and 4.7degrees respectively in 150% magnified images. CONCLUSION: In computerized measurements for angular parameters of hallux valgus with digital radiography, 150% magnified images showed intraobserver reliability. Both 100% and 150% magnified images failed to show interobserver reliability. Measurement of 1-2 IMA in both 100% and 150% images showed less interobserver error.

Clinical Significance of Transrectal Ultrasonography and Efficacy of Dutasteride Treatment in Patients with Hemospermia / 대한남성과학회지

PURPOSE: The aims of this study were to investigate the clinical significance of transrectal ultrasonography (TRUS) and the efficacy of dutasteride (5alpha-reductase inhibitor) in patients with hemospermia. MATERIALS AND METHODS: From January 2005 to December 2008, 60 patients with hemospermia were enrolled in the study. All patients underwent a digital rectal examination and TRUS; serum prostate specific antigen was also measured. The management of hemospermia was one of the following: watchful waiting, dutasteride treatment, or antibiotics with dutasteride. RESULTS: Thirty-four patients (56.7%) had positive findings on TRUS. There were 16 cases (26.7%) of prostate calcification, 13 cases (21.7%) of ejaculatory duct cyst, 3 cases (5%) of ejaculatory duct calcification, a case of seminal vesicle inflammation, and a case of ejaculatory duct dilation. Dutasteride treatment resulted in improvement of symptoms in 87.9% (29/33) of the cases, whereas treatment with antibiotics or antibiotics with dutasteride resulted in a 100% (6/6) success rate. However, among 14 watchful waiting patients, only 3 patients (21.4%) showed an improvement of symptoms. CONCLUSIONS: This study showed that TRUS is an easy and effective method for the assessment of hemospermia, and also revealed that dutasteride could be a useful agent in the treatment of hemospermia.

Changes in Sexual Function in Benign Prostatic Hyperplasia Patients Taking Dutasteride: 1-Year Follow-Up Results

PURPOSE: Sexual adverse events (AEs), a major cause for discontinuing 5alpha-reductase inhibitor (5ARI) therapy for benign prostatic hyperplasia (BPH), are known to occur most frequently early in therapy and appear to decline over time. The aim of this study was to investigate the changes in sexual function occurring with dutasteride treatment during a 1-year follow-up period in Korean men. MATERIALS AND METHODS: Using the International Index of Erectile Function, we prospectively evaluated, after 1, 3, 6, 9, and 12 months of treatment, the changes in sexual function of 55 outpatients (mean age 62.3+/-7.2 years) with BPH (mean volume 48.9+/-16.0 g) who had relatively good erectile function (EF) and were treated with dutasteride for at least 1 year. RESULTS: EF scores showed the most significant decrease at 1 month (p<0.01). Function gradually recovered thereafter but was still significantly decreased after 12 months of treatment (p<0.05). The scores for orgasmic function and sexual desire also showed the most significant reduction at 1 month but were restored to the baseline level at 6 months. No significant correlation was observed between changes in sexual function and prostate-specific antigen level, prostate volume, or International Prostate Symptom Scores. CONCLUSIONS: After 1 month of treatment, dutasteride therapy resulted in a significant reduction in all investigated sexual functions. Overall, recovery in sexual function was noted at 3 months, and orgasmic function and sexual desire were restored to baseline levels at 6 months. However, EF was still significantly reduced at 12 months.

Drug treatment for lower urinary tract symptoms

Lower urinary tract symptoms (LUTS) are classified into three groups: storage, voiding, and post-micturition symptoms. The most popular causes of LUTS are benign prostatic hyperplasia (BPH) and overactive bladder (OAB). Although BPH is a pathologic term, clinically, we use this when patients have LUTS due to benign prostatic enlargement and obstruction. OAB is defined as urgency, with or without urge incontinence, usually with frequency and nocturia. Currently alpha1-adrenoceptor antagonists are the most common drug treatment for BPH, and are thought to act by relaxing the prostatic smooth muscle. They are all effective for the treatment of LUTS/BPH. 5alpha-reductase inhibitors, such as fiansteride and dutasteride, are another treatment option for BPH symptoms, which reduce the prostatic volume by inducing epithelial atrophy. Long-term combination therapy with alpha-1-blockers and 5alpha-reductase inhibitors reduces the risk of the overall clinical progression of BPH significantly more than does treatment with either drug alone. Antimuscarinics are the mainstay for the treatment of OAB. Antimuscarinics competitively block muscarinic receptors of all subtypes but with variations in selectivity for the different subtypes. When they are used for the treatment of OAB, they are active during the storage phase of the bladder, with little or no effect on voiding contractions. Desmopressin acetate is a synthetic analogue of Arginin vasopressin, which has been proven effective for the treatment of nocturnal polyuria in LUTS.

Dutasteride in the treatment of benign prostatic hyperplasia: an update / 中华男科学杂志

Benign prostatic hyperplasia (BPH) is a common disease in older men. At present, 5alpha reductase inhibitor-based medication, preferred by most BPH patients as the first-choice therapy, is taking place of traditional transurethral resection of the prostate. This article presents an update of the researches on the treatment of BPH with dutasteride--a novel 5 alpha-reductase inhibitor.

The Effect of 5-alpha Reductase Inhibitors on the Efficacy of Photoselective Vaporization of the Prostate with 120 W GreenLight HPS Laser / 대한남성과학회지

PURPOSE: To evaluate the effect of preoperative 5-alpha reductase inhibitor (ARI) administration on the operative results of photoselective vaporization of prostate with 120W GreenLight HPS laser. MATERIALS AND METHODS: Data were collected from 98 benign prostatic hyperplasia (BPH) patients who underwent transurethral electrovaporization of prostate by 120W Greenlight HPS laser between Jan. 2010 and Dec. 2010. We compared the time of operation, the energy required in lasering, postoperative maximum uroflow velocity, change in residual urine volume and complications between 5-ARI administrating group and control group. RESULTS: 56 patients administrated 5-ARI at least 3 months before surgery. 30 and 26 patients administrated finasteride and dutasteride, respectively. Mean follow up period was 4.1+/-1.8 months. Mean age of the subjects and mean prostate volume were not different. Mean change of postoperative hemoglobin, lasing time and energy required in lasering were greater in 5-ARI administrating group. There were 3 and 1 cases of acute urinary retension in 5-ARI administrating group and control group, respectively. CONCLUSIONS: The mean change of hemoglobin and mean energy required in lasering were greater and mean lasing time was longer in the patients who administrated 5-ARI before photoselective vaporization of prostate by 120W Greenlight HPS laser. Further investigation and extensive study will be needed to confirm these results.

Prevention of Prostate Cancer

Prostate cancer can be prevented more easily than other types of cancers, thanks to the following reasons: The presence of precursor lesions, longer doulbling time of cancerous cells, high incidence and prevalence, and susceptibility to chemo-preventive agents such as 5 alpha reductase inhibitor (5ARI). The following risk factors may increase the incidence of prostate cancer: age (older than 50), family history of prostate cancer, race (African-American), hormones (testosterone, dehydrotestosterone), and diet high in dairy foods and calcium. The following protective factors may decrease the risk of prostate cancer: Lycopene, Soy, Green tea, Vit. D, and taking Finasteride or Dutasteride. The following have not been proven to prevent prostate cancer: Selenium, vitamin E, retinoid, and multivitamins. However, their effectiveness is still under investigation. Avoiding risk factors such as smoking, being overweight and lack of exercise may help prevent cancers. Increasing protective factors such as quitting smoking, eating a healthy diet and exercising may also help prevent cancers. Some clinical studies are conducted on polyphenon E for high grade PIN, Vitamin D, fish oil, green tea, and aspirin for prostate cancer prevention. Prostate cancer is an attractive and appropriate target for cancer prevention because of its incidence, prevalence and disease-related mortality. In addition to changing life style with healthy food and reducing dairy and calcium intake, taking certain drugs (5ARI) may prevent cancer development.

The Different Reduction Rate of Prostate-Specific Antigen in Dutasteride and Finasteride

PURPOSE: To compare and analyze the therapeutic effects and changes in the prostate-specific antigen (PSA) level with treatment with finasteride or dutasteride for benign prostatic hyperplasia (BPH) for 1 year. MATERIALS AND METHODS: We retrospectively investigated patients who suffered from BPH for 1 year between January 2005 and December 2008. For treatment groups, we divided the patients into two groups: one was treated with alfuzosin and finasteride and the other was treated with alfuzosin and dutasteride. At the beginning of treatment, the patients underwent transrectal ultrasonography and measurement of urine flow rate, residual urine volume, PSA, and International Prostate Symptom Score (IPSS). Patients with diseases affecting urinary function were excluded. We not only analyzed the data at the time of initial treatment, but also after 1 year of treatment. A total of 219 patients were able to be evaluated for 1 year. RESULTS: Both finasteride and dutasteride reduced PSA and prostate volume significantly. The comparison between groups showed a more significant reduction of PSA (p=0.020) and prostate volume (p=0.052) in the dutasteride group. Other parameters did not differ significantly between the groups. CONCLUSIONS: 5-alpha Reductase inhibitors for BPH treatment reduced PSA and prostate volume significantly when the patients were treated for 1 year. Administration of dutasteride is considered to be more effective in reducing PSA and prostate volume. Therefore, dutasteride should not be considered equivalent to finasteride in the reduction rate of PSA. The intensity of dutasteride must be reevaluated in comparison with finasteride.

Association of Polymorphisms in the Prostate-Specific Antigen (PSA) Gene Promoter with Serum PSA Level and PSA Changes after Dutasteride Treatment in Korean Men with Benign Prostatic Hypertrophy

PURPOSE: Studies of genetic variation in the prostate-specific antigen (PSA) gene have improved the diagnostic accuracy of PSA for diagnosing prostate diseases in Caucasians. However, the reference ranges and pharmacokinetics of PSA differ significantly according to race. Therefore, we evaluated the association between genetic variations in the PSA promoter area and benign prostatic hyperplasia (BPH) phenotypes in Korean BPH patients. MATERIALS AND METHODS: One hundred twenty-one men were enrolled. The initial serum PSA level, prostate size, and PSA changes at 3 months after treatment with dutasteride were determined. We amplified the promoter region of the PSA gene (nucleotide positions -158 to -356 and -5217 to -5429) and sequenced the products. RESULTS: Three relatively well characterized single-nucleotide polymorphisms (SNPs; rs3760722, rs266867, and rs266868), six uncharacterized SNPs (rs17554958, rs266882, rs4802754, rs2739448, rs2569733, and rs17526278), and one novel SNP (nucleotide position -5402) were found. There were no statistically significant correlations between any of the SNPs of the PSA promoter area and age-adjusted prostate sizes, initial PSA levels, or PSA variations after 3 months of dutasteride treatment. CONCLUSIONS: SNPs in the PSA promoter area were not associated with BPH phenotypes. We could not predict serum PSA changes after dutasteride treatment on the basis of PSA promoter genotype in Korean patients with BPH.