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

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

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

No abstract available.
Alopecia* ; Dutasteride* ; Finasteride*

BACKGROUND: After the approval of dutastride for androgenic alopecia (AGA) in 2009, Korean authority required a post-marketing surveillance to obtain further data on its safety profile. OBJECTIVE: The objective was to monitor adverse events (AEs) of dutasteride 0.5 mg in Korean AGA male patients in a clinical practice environment. METHODS: Open label, multi-center, non-interventional observational study was done from July 2009 to July 2013. AGA subjects (18~41 years of age) with no experience of dutasteride were enrolled. Dosage regimen was recommended according to the prescribing information. The incidences of any AEs, serious adverse events (SAEs), and adverse drug reactions (ADRs) were evaluated. Multiple logistic regression method was used to identify risk factors related to ADRs. Effectiveness was generally evaluated by physicians. RESULTS: During study period, 712 subjects were enrolled. The subjects of 29.3±6.0 years old exposed to dutasteride for 204.7±161.5 days. One hundred and ten (15.4%) of subjects reported 138 AEs. Four subjects (0.6%) reported 5 SAEs (right radius fracture, 2 events of chronic follicular tonsillitis, influenza infection, and acute appendicitis). Sixty-six subjects (9.3%) reported 80 ADRs. Most frequent ADRs were libido decreased (9 subjects, 1.3%), dyspepsia (8 subjects, 1.1%), impotence (7 subjects, 1.0%), and fatigue (5 subjects, 0.7%). Other interested ADRs were sexual function abnormality (4 subjects, 0.6%), gynecomastia (2 subjects, 0.3%), and ejaculation disorder (1 subject, 0.1%). Most subjects (78.6%) showed overall improvement after treatment of dutasteride in the effectiveness. CONCLUSION: Dutasteride 0.5 mg is to be well-tolerated in 18 to 41 years old AGA patients in a clinical practice environment.
Alopecia* ; Drug-Related Side Effects and Adverse Reactions ; Dutasteride* ; Dyspepsia ; Ejaculation ; Erectile Dysfunction ; Fatigue ; Gynecomastia ; Humans ; Incidence ; Influenza, Human ; Libido ; Logistic Models ; Male ; Methods ; Observational Study ; Oxidoreductases* ; Palatine Tonsil ; Radius Fractures ; Risk Factors ; Tonsillitis ; Treatment Outcome

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

Dual inhibition of both 5AR1 and 5AR2 by dutasteride provides greater and more consistent inhibition of the conversion of testosterone to dihydrotestosterone (DHT) than selective inhibition of 5AR2 alone. Beyond the benefit of symptomatic improvement in lower urinary tract symptoms/benign prostatic hyperplasia by dutasteride, recently, several pioneering studies have shown cancer-protective roles of dutasteride in localized prostate cancer. This can be summarized into two categories: management of biochemical recurrence after radical therapy and management of active surveillance of low-risk prostate cancer. This review concerns the rationale and superiority of dutasteride as a cancer-protective agent in localized prostate cancer and its possible mechanisms, reinforced by two recent randomized controlled trials, the Avodart after radical therapy for prostate cancer study ("ARTS") and reduction by dutasteride of clinical progression events in expectant management ("REDEEM") studies.
Dihydrotestosterone ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms* ; Recurrence ; Testosterone ; Urinary Tract ; Dutasteride

PURPOSE: Dutasteride affects the prostate by reducing intraprostatic dihydrotestosterone and prostate tissue vascularity. We evaluated the effect of pretreatment with dutasteride for two weeks on perioperative and postoperative bleeding during transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Eighty-three patients who had benign prostatic hyperplasia together with the criteria for eligibility for TURP were included. The dutasteride group consisted of 40 patients who were treated with dutasteride (0.5 mg/d) for two weeks before surgery, and the control group consisted of 43 patients who did not receive dutasteride. Blood loss was evaluated in terms of reduction in serum hemoglobin (Hb) and hematocrit (Hct) levels, which were measured before, immediately after, and 24 hours after surgery. We also measured the durations of indwelling urethral catheter use, continuous saline bladder irrigation, and hospitalization. RESULTS: Lower mean blood loss was observed in the dutasteride group than the control group immediately after and 24 hours after surgery (DeltaHb=0.65+/-1.27 g/dL vs. 1.16+/-0.73 g/dL, 1.30+/-1.00 g/dL vs. 1.86+/-1.05 g/dL respectively, p=0.019, p=0.011; DeltaHct=1.89%+/-3.83% vs. 3.47%+/-2.09%, 3.69%+/-2.95% vs. 5.39%+/-3.23% respectively, p=0.016, p=0.011). In addition, there were fewer days of indwelling urethral catheter use (2.95+/-1.02 d vs. 3.92+/-1.14 d, p=0.000), continuous saline bladder irrigation (1.81+/-1.08 d vs. 2.36+/-1.06 d, p=0.016), and hospitalization after TURP (3.95+/-1.09 d vs. 4.76+/-1.19 d, p=0.001) in the dutasteride group. CONCLUSIONS: Preoperative treatment with dutasteride for two weeks before TURP reduces surgical bleeding and length of hospitalization after TURP. This pretreatment can be used to decrease surgical bleeding associated with TURP.
Dihydrotestosterone ; Hematocrit ; Hemorrhage* ; Hospitalization ; Humans ; Prostate* ; Prostatic Hyperplasia ; Transurethral Resection of Prostate ; Urinary Bladder ; Urinary Catheters ; Dutasteride

BACKGROUND: Androgenetic alopecia (AGA), one of alopecias, requires continuous treatment in order to prevent or stop it, and patient's compliance is very important. Currently, only two drugs (finasteride, minoxidil) have been approved for AGA by Food and Drug Administration of United States (US FDA). However, another alpha-2 reductase inhibitor, dutasteride, is approved by Korea Ministry of Food and Drug Safety (MFDS) through a phase III trial. For treatment, pharmacotherapy of AGA usually combines topical minoxidil 7% with one of oral alpha-2 reductase inhibitor. OBJECTIVES: We evaluated the comparative efficacy and adverse effect between topical minoxidil 7%/finasteride 1 mg and topical minoxidil 7%/dutasteride 0.5 mg pharmacotherapy for outpatients with AGA. Also we evaluated the relationship between therapeutic effect and regular hospital visit. METHOD: This study was performed retrospectively based on electronic medical record (EMR) data of total 98 patients (topical minoxidil 7% with dutasteride 0.5 mg (Avodart(R)) or finasteride 1 mg (Alopecia(R), Propecia(R)) with diagnosis of AGA from department of dermatology at a secondary hospital from January 1st, to May 31st, 2014. RESULTS: The efficacy and adverse event of topical minoxidil 7%/dutasteride 0.5 mg (DUTA group) were 100% and 45.7%, and of topical minoxidil 7%/finasteride 1 mg (FINA group) were 92.1% and 33.3%, respectively. The mean onset time of responses and adverse events in the FINA group were 3.86 months and 4.43 months. Those in the DUTA group were 3.97 months and 5.06 months. CONCLUSION: Both FINA and DUTA group were highly effective, but the DUTA group showed higher efficacy and adverse effects than those in the FINA group. Dutasteride may be another alternative in AGA treatment.
Alopecia* ; Compliance ; Dermatology ; Diagnosis ; Drug Therapy ; Electronic Health Records ; Finasteride ; Humans ; Korea* ; Minoxidil ; Outpatients ; Oxidoreductases ; Retrospective Studies* ; United States ; United States Food and Drug Administration ; Dutasteride

OBJECTIVETo 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.

METHODSSixteen 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.

RESULTSDutasteride 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).

CONCLUSIONDutasteride 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.

Animals ; Azasteroids ; pharmacology ; Claudin-1 ; metabolism ; Dihydrotestosterone ; blood ; Dutasteride ; Epididymis ; drug effects ; metabolism ; Female ; Fertility ; drug effects ; Humans ; Intercellular Junctions ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testosterone ; blood ; Urological Agents ; pharmacology ; beta Catenin ; metabolism