Humans ; Finasteride/pharmacology* ; Dutasteride/pharmacology* ; 5-alpha Reductase Inhibitors/pharmacology* ; Testosterone/metabolism* ; Hair Follicle/metabolism* ; Transcriptome ; Hair/metabolism*

The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-β-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(trans-urticol-7-O-β-D-glucopyranoside, 7), cycloolivil-4-O-β-D-glucopyranoside(8), isolariciresinol-4'-O-β-D-glucopyranoside(9), and olivil-4'-O-β-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.
5-alpha Reductase Inhibitors ; Cholestenone 5 alpha-Reductase/pharmacology* ; Chromatography, High Pressure Liquid ; Lignans/pharmacology* ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Urticaceae/enzymology*

PURPOSE: The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was associated with higher rate of permanent erectile dysfunction (ED) in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats (n=76) were assigned to five groups: (i) normal control group; (ii) dutasteride (0.5 mg/rat/d) for 4-weeks group; (iii) dutasteride for 4-weeks plus 2-weeks of resting group; (iv) dutasteride for 8-weeks group; and (v) dutasteride for 8-weeks plus 2-weeks of resting group. In vivo erectile responses to electrical stimulation, and changes of fibrotic factors and smooth muscle/collagen contents in the corpus cavernosum were evaluated in each group. RESULTS: Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period. CONCLUSIONS: Our study showed that recovery from ED depended on the duration of medication, and administration of dutasteride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.
5-alpha Reductase Inhibitors ; Administration, Oral ; Animals ; Collagen ; Dutasteride ; Electric Stimulation ; Erectile Dysfunction ; Finasteride ; Humans ; Male ; Models, Animal ; Muscle, Smooth ; Oxidoreductases ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factors

PURPOSE: To evaluate parameters for determining repeat prostate biopsy in patients with 5α-reductase inhibitor (5ARI) treatment after initial negative biopsy. MATERIALS AND METHODS: From January 2007 to December 2015, patients who underwent a repeat prostate biopsy after an initial negative biopsy were enrolled from multiple institutions. Serial prostate-specific antigen (PSA) levels after the initial biopsy were analyzed for PSA kinetics. Clinicopathologic variables were evaluated according to the use of 5ARIs after the initial negative biopsy. RESULTS: Of 419 patients with initial negative biopsies (median age=67.0 years, median PSA=6.31 ng/mL), 101 patients (24.1%) were diagnosed with prostate cancer at the repeat biopsy. An increase in PSA level at 18 months, compared to that at 6 months, was a predictor of a positive repeat biopsy. However, the use of 5ARIs was not identified as a predictor. Of 126 patients receiving 5ARI treatment after the initial biopsy, 30 (23.8%) were diagnosed with prostate cancer at the repeat biopsy. Increase in PSA level at more than two time points after 6 months of 5ARI treatment (odds ratio=4.84, p=0.005) was associated with cancer detection at the repeat biopsy. There were no significant 5ARI group-related differences in the detection rates of prostate and high-grade cancers (Gleason score ≥7). CONCLUSION: The effects of 5ARIs on prostate cancer detection and chemoprevention remain uncertain. However, more than two increases in PSA level after 6 months of 5ARI treatment may indicate the presence of prostate cancer.
5-alpha Reductase Inhibitors/*therapeutic use ; Aged ; *Biopsy ; Follow-Up Studies ; Humans ; Kinetics ; Male ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/blood/*drug therapy/*pathology

PURPOSE: The 5-alpha reductase inhibitors (5ARI) are one of the most commonly used medications for the treatment of benign prostatic hyperplasia (BPH). Phosphodiesterase type-5 inhibitors are also used to treat BPH. 5ARI is a drug with adverse effects of sexual dysfunction. In this study, we investigated the safety and efficacy of coadministration of finasteride and sildenafil on sexual function and lower urinary symptoms in patients with BPH. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who were receiving finasteride and sildenafil daily regimens for treatment of BPH in 2 university hospitals. Patients with adverse effects, vital sign, physical exam, laboratory test, 5-item version of the international index of erectile function (IIEF-5), International Prostate Symptom Score (IPSS), quality of life (QoL) were analyzed. RESULTS: The number of patients analyzed in this study was 218. The mean age of the patients was 62.63±8.37 years and the mean duration of medication was 18.23±10.97 weeks. Significant changes were not observed in the vital signs measured before and after the drug administration. Compared with before treatment, improvement of lower urinary tract symptom (IPSS: 17.56±4.21 vs. 11.64±5.33, p < 0.001) was observed and improvement of sexual function (IIEF-5: 9.44±5.21 vs. 12.73±6.81, p < 0.001) was also confirmed. CONCLUSIONS: Daily coadministration of finasteride and sildenafil for the treatment of BPH could be used safely, and improvement of lower urinary tract symptom as well as improvement of sexual function could be expected.
5-alpha Reductase Inhibitors ; Erectile Dysfunction ; Finasteride ; Hospitals, University ; Humans ; Lower Urinary Tract Symptoms ; Male ; Medical Records ; Prostate ; Prostatic Hyperplasia ; Quality of Life ; Retrospective Studies ; Sildenafil Citrate ; Urinary Tract ; Vital Signs

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia (BPH) rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups: C, untreated control rats; C + D, control rats receiving dutasteride; C + F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats (SHRs); H + D, SHRs treated with dutasteride; and H + F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density (Sv) of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni's posttest. Groups C + D and C + F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C + D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H + D and H + F had less smooth muscle Sv than Group H. Group H + D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was greater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.
5-alpha Reductase Inhibitors/therapeutic use* ; Animals ; Disease Models, Animal ; Dutasteride/therapeutic use* ; Finasteride/therapeutic use* ; Male ; Muscle, Smooth/pathology* ; Myocytes, Smooth Muscle/pathology* ; Penis/pathology* ; Prostate/pathology* ; Prostatic Hyperplasia/pathology* ; Rats

PURPOSE: To compare the current management of benign prostatic hyperplasia (BPH) by urologists and nonurologists by use of Korean nationwide health insurance data. MATERIALS AND METHODS: We obtained patient data from the national health insurance system. New patients diagnosed with BPH in 2009 were divided into two groups depending on whether they were diagnosed by a urologist (U group) or by a nonurologist (NU group). RESULTS: A total of 390,767 individuals were newly diagnosed with BPH in 2009. Of these, 240,907 patients (61.7%) were in the U group and 149,860 patients (38.3%) were in the NU group. The rate of all initial evaluation tests, except serum creatinine, was significantly lower in the NU group. The initial prescription rate was higher in the U group, whereas the prescription period was longer in the NU group. Regarding the initial drugs prescribed, the use of alpha-blockers was common in both groups. However, the U group was prescribed combination therapy of an alpha-blocker and 5-alpha-reductase inhibitor as the second choice, whereas the NU group received monotherapy with a 5-alpha-reductase inhibitor. During the 1-year follow-up, the incidence of surgery was significantly different between the U group and the NU group. CONCLUSIONS: There are distinct differences in the diagnosis and treatment of BPH by urologists and nonurologists in Korea. These differences may have adverse consequences for BPH patients. Urological societies should take a leadership role in the management of BPH and play an educational role for nonurologists as well as urologists.
5-alpha Reductase Inhibitors/therapeutic use ; Adrenergic alpha-Antagonists/therapeutic use ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Databases, Factual ; *Disease Management ; Humans ; Insurance, Health ; Linear Models ; Male ; Middle Aged ; Physicians ; Prostatic Hyperplasia/*diagnosis/*therapy ; Republic of Korea ; Urology/*methods ; Young Adult

OBJECTIVETo evaluated the safety and effect of the 120-W GreenLight HPS laser photoselective vaporization of the prostate (PVP) in different BPH populations.

METHODSThis study included 174 BPH patients treated by PVP using 120-W Green-Light HPS laser. According to the prostate volume (PV) ( < 80 or ≥ 80 ml), history of 5-alpha reductase inhibitor (5-ARI) medication, and history of acute urinary retention (AUR), we divided the patients into a PV < 80 ml, a PV ≥ 80 ml, a 5-ARI, a no 5-ARI; an AUR, and a no AUR group. We collected the baseline, perioperative, and follow-up data about the patients, and compared them among different groups.

RESULTSThe patients were aged 69.4 ± 7.7 years, of whom PVP was successfully performed for 136 and PVP was intraoperatively converted to transurethral resection of the prostate (TURP) in the other 38, with a mean operation time of (49.4 ± 16.3) min. The preoperative PV averaged (67.9 ± 29.8) ml. There was no intraoperative blood transfusion, transurethral resection syndrome, or capsule perforation. Bladder neck contracture occurred in 2 cases and urethral stricture developed in another 2 postoperatively. All the patients showed a significant improvement in the prostatic function parameters and no significant differences were observed between the PV < 80 ml and PV ≥ 80 ml, 5-ARI and no 5-ARI, or AUR and no AUR groups.

CONCLUSIONPVP with 120-W GreenLight HPS laser is safe and efficient for the treatment of BPH and the its effect is not influenced by the prostate volume, history of 5-ARI medication, or history of AUR. However, preoperative urinary catheterization may increase the difficulty of surgery and the risk of conversion to TURP.

5-alpha Reductase Inhibitors ; therapeutic use ; Aged ; Humans ; Laser Therapy ; adverse effects ; methods ; Male ; Operative Time ; Organ Size ; Prostate ; pathology ; surgery ; Prostatic Hyperplasia ; pathology ; surgery ; Transurethral Resection of Prostate ; Treatment Outcome ; Urethral Stricture ; etiology ; Urinary Bladder ; Urinary Retention

PURPOSE: We conducted a prospective single-center study to evaluate the possibility of discontinuation of dutasteride after combination therapy with an alpha blocker for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We prospectively treated BPH patients with an alpha blocker and dutasteride (0.5 mg/d). Patients who had been treated with alpha blockers against BPH for more than 2 months were eligible, and 20 patients were included in the study. After 6 months of combination therapy, dutasteride was discontinued. Patients were followed for 12 months after cessation. Prostate volume, intraprostatic architecture determined by transrectal ultrasound, peak urinary flow rate, postvoid residual urine volume, and the serum prostate-specific antigen level were evaluated every 6 months, and the International Prostate Symptom Score and overactive bladder symptom score (OABSS) every 3 months. Patients were allowed to restart dutasteride during the follow-up period according to their desire. RESULTS: Twelve patients (12/20, 60%) restarted the combination therapy from 6 to 12 months into the follow-up period. For patients who restarted dutasteride, the prostate volume and OABSS had increased and worsened after discontinuation, respectively. A visible transition zone with a clear border on transrectal ultrasound at baseline and regrowth of the prostate after discontinuation of dutasteride were risk factors for restarting the therapy (Mann-Whitney U test: p=0.008, p=0.017). CONCLUSIONS: Prostatic enlargement after discontinuation of dutasteride differs among patients. Rapid regrowth of the prostate leads to deterioration of storage symptoms and a tendency to restart dutasteride. Baseline intraprostatic architecture may be a predictive factor for whether the patient is a good candidate for discontinuation.
5-alpha Reductase Inhibitors/administration & dosage/adverse effects ; *Adrenergic alpha-Antagonists/administration & dosage/adverse effects ; Aged ; Drug Monitoring ; Drug Therapy, Combination/methods ; *Dutasteride/administration & dosage/adverse effects ; Follow-Up Studies ; Humans ; Japan ; Male ; Middle Aged ; Organ Size ; Prospective Studies ; *Prostate/drug effects/pathology/ultrasonography ; Prostate-Specific Antigen/analysis ; *Prostatic Hyperplasia/drug therapy/pathology ; Secondary Prevention/methods/statistics & numerical data ; Treatment Outcome ; Withholding Treatment

PURPOSE: To assess changes in lower urinary tract symptoms (LUTS), prostate volume, and serum prostate-specific antigen (PSA) after discontinuation of 5-alpha reductase inhibitor (5ARI) combination therapy in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: From December 2003 to December 2012, data were collected retrospectively from 81 men more than 40 years of age with moderate to severe BPH symptoms (International Prostate Symptom Score [IPSS]> or =8). The men were classified into group 1 (n=42) and group 2 (n=39) according to the use of 5ARI therapy. A combination of dutasteride 0.5 mg with tamsulosin 0.2 mg was given daily to all patients for 1 year. For the next 1 year, group 1 (n=42) received the combination therapy and group 2 (n=39) received tamsulosin 0.2 mg monotherapy only. The IPSS, prostate volume, and PSA level were measured at baseline and at 12 and 24 months according to the use of dutasteride. RESULTS: Discontinuation of dutasteride led to significant deterioration of LUTS, increased prostate volume, and increased PSA level. The repeated-measures analysis of variance showed that the changes in IPSS, prostate volume, and PSA level over time also differed significantly between groups 1 and 2 (p<0.001). CONCLUSIONS: Withdrawal of 5ARI during combination therapy resulted in prostate regrowth and deterioration of LUTS. The PSA level is also affected by the use of 5ARI. Therefore, regular check-up of the IPSS and PSA level may be helpful for all patients who either continue or discontinue the use of 5ARI.
5-alpha Reductase Inhibitors ; Humans ; Lower Urinary Tract Symptoms ; Male ; Oxidoreductases* ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Retrospective Studies