Use Of 5α-reductase Inhibitors Research Articles

(068) The Men’s Training Cup Keep Training: A Masturbation Aid Improves Intravaginal Ejaculatory Latency Time and Erection Hardness Score in Patients who are Unable to Delay Ejaculation

Abstract Introduction Premature ejaculation (PE) has negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. In Japan, no oral drugs or devices are approved or used clinically to treat PE. The Men’s Training Cup Keep Training (MTCK), a masturbation aid, was developed for PE. MTCK offers 5 grades of tightness and strength. Objective We aimed to investigate the efficacy of the MTCK in patients who are unable to delay ejaculation. Methods Inclusion criteria were 20- to 60-year-old men feeling distressed and frustrated by PE and who had the same sexual partners throughout the study period. Exclusion criteria were neurologic disease and uncontrolled diabetes mellitus, as well as the use of antidepressants, α-blockers, and 5α-reductase inhibitors. The protocol comprised an 8-week training period with the MTCK from level 1 to level5, with each level used twice before moving to the next level. The main outcome measure was the extension of intravaginal ejaculation latency time (IELT). The secondary outcome measures were score improvements on the Premature Ejaculation Diagnostic Tool, Sexual Health Inventory for Men, Erection Hardness Score, and Difficulty in Performing Sexual Intercourse Questionnaire–5. Results We enrolled 37 patients, and after 19 patients withdrew, 18 concluded the study without experiencing any adverse events. The mean patient age was 39.9 years. Geometric IELT after the 8 week training with the MTCK increased significantly (mean ± SE; 232.10 ± 72.16 seconds) vs baseline (103.91 ± 50.61 seconds, P=.006). Mean scores on the Premature Ejaculation Diagnostic Tool, Difficulty in Performing Sexual Intercourse Questionnaire–5, and Erection Hardness Score after 8-week training improved significantly vs the baseline values. The mean score on the Sexual Health Inventory for Men did not improve significantly after the 8-week training, but domain 1 did significantly improve after 8 weeks of MTCK use. Conclusions The MTCK may be one possible treatment option for patients who are unable to delay ejaculation. Also, the MTCK may offer benefits for erectile function. Disclosure No.

Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study

Background We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. Methods This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. Results Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). Conclusion This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

The Men's Training Cup Keep Training: a masturbation aid improves intravaginal ejaculatory latency time and Erection Hardness Score in patients who are unable to delay ejaculation.

Premature ejaculation (PE) has negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. In Japan, no oral drugs or devices are approved or used clinically to treat PE. The Men's Training Cup Keep Training (MTCK), a masturbation aid, was developed for PE. MTCK offers 5 grades of tightness and strength. We aimed to investigate the efficacy of the MTCK in patients who are unable to delay ejaculation. Inclusion criteria were 20- to 60-year-old men feeling distressed and frustrated by PE and who had the same sexual partners throughout the study period. Exclusion criteria were neurologic disease and uncontrolled diabetes mellitus, as well as the use of antidepressants, α-blockers, and 5α-reductase inhibitors. The protocol comprised an 8-week training period with the MTCK from level 1 to level 5, with each level used twice before moving to the next level. The main outcome measure was the extension of intravaginal ejaculation latency time (IELT). The secondary outcome measures were score improvements on the Premature Ejaculation Diagnostic Tool, Sexual Health Inventory for Men, Erection Hardness Score, and Difficulty in Performing Sexual Intercourse Questionnaire-5. We enrolled 37 patients, and after 19 patients withdrew, 18 concluded the study without experiencing any adverse events. The mean patient age was 39.9years. Geometric IELT after the 8-week training with the MTCK increased significantly (mean ± SE; 232.10 ± 72.16seconds) vs baseline (103.91 ± 50.61seconds, P = .006). Mean scores on the Premature Ejaculation Diagnostic Tool, Difficulty in Performing Sexual Intercourse Questionnaire-5, and Erection Hardness Score after 8-week training improved significantly vs the baseline values. The mean score on the Sexual Health Inventory for Men did not improve significantly after the 8-week training, but domain 1 did significantly improve after 8weeks of MTCK use. The MTCK may be one possible treatment option for patients who are unable to delay ejaculation. This is the first study to show that the MTCK is effective for patients who are unable to delay ejaculation. A major limitation is that the present study was not strictly limited to an IELT <3minutes. The MTCK may offer benefits not only for delay of ejaculation but also for erectile function.

Persistence to Medications for Benign Prostatic Hyperplasia/Benign Prostatic Obstruction-Associated Lower Urinary Tract Symptoms in the ASL TO4 Regione Piemonte (Italy).

Pharmacological treatment of benign prostatic hyperplasia (BPH)/benign prostatic obstruction (BPO)-associated lower urinary tract symptoms (LUTS) aims at improving patients' quality of life by managing urinary symptoms and preventing complications and disease progression. However, continuous use of drugs to treat BPH/BPO-associated LUTS decreases over time. The aim of this retrospective observational study was to describe use of α1-adrenoceptor antagonists (ABs) and steroid 5α-reductase inhibitors (5ARIs) by adult (age ≥ 40 years) men in the ASL TO4, a Local Health Authority in the northern area of the city of Turin (Italy). Persistence measures were adopted as a robust, informative, and feasible way to understand medication-taking behavior and to assess patient compliance. A total of 4309 men (median age 71 years) were enrolled. Monotherapy was the treatment option prescribed to the largest part of the study population. However, ≥two drugs were prescribed to a substantial proportion of men (23%). Men prescribed alfuzosin or dutasteride had significantly greater persistence, which decreased over time. Unmet needs and areas of intervention for healthcare systems aimed at improving the use of drugs for BHP/BPO-associated LUTS in the ASL TO4 Regione Piemonte were identified.

The Effect of Protective Coil Embolization of Penile Anastomoses during Prostatic Artery Embolization on Erectile Function: A Propensity-Matched Analysis

PurposeTo explore whether coil embolization of penile collateral arteries to prevent nontarget embolization during prostatic artery embolization (PAE) negatively affects erectile function. Materials and MethodsRetrospective analysis was performed on a prospectively maintained multicenter PAE database on all patients with benign prostatic hyperplasia (January 2014 to July 2016). International Index of Erectile Function (IIEF-5) scores were collected at baseline and within 12 months after the procedure. A logistic regression and nearest neighbor propensity-matched analysis (matched for age, baseline IIEF-5 scores, and use of 5α-reductase inhibitors) and paired t test were used to evaluate for differential impact on IIEF-5 scores between the group of patients who underwent (unilateral) penile collateral coil embolization and a matched control group of patients who did not. ResultsOf a total of 216 patients, 26 underwent coil protection of an accessory pudendal vessel/penile collateral. After exclusions, 22 propensity-matched pairs were identified. The mean IIEF-5 score at baseline for the coil-embolized group was 14.8 ± 8.3 (out of a possible score of 30) and that for the matched control group was 14.0 ± 7.8. At the 12-month follow-up after the procedure, the mean follow-up IIEF-5 score was 15.5 ± 8.0 for the coil-embolized group and 14.2 ± 8.2 for the matched control group. The change in IIEF-5 scores after PAE was not significantly different between the 2 groups (0.66 ± 3.8 vs 0.20 ± 2.0; P = .64; 95% CI, -1.53 to 2.44). ConclusionsWhen penile collateral arteries were identified, protective coil embolization of penile collateral/accessory pudendal vessels during PAE was unlikely to affect erectile function negatively.

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site

BackgroundTo investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site.MethodsA Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed.ResultsThe cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82–1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80–1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39–0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37–0.65).ConclusionUsers of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.

Depression risk associated with the use of 5α-reductase inhibitors versus α-blockers: A retrospective cohort study in South Korea

BackgroundOne of the most prescribed treatments for benign prostatic hyperplasia (BPH) is 5α-reductase inhibitors (5ARI). Europe experienced recent safety issues involving 5ARI and depression symptoms, with similar findings being seen in Western countries. The South Korea has updated the drug label in accordance with European recommendations, but the relevant evidence was insufficient. This study compared the use of 5ARI versus α-blocker (AB) as a treatment for BPH and related risks of depression to provide evidence based on the Korean population.MethodsThis was a retrospective cohort study using South Korea’s Health Insurance Review & Assessment Service claim data from 2011 to 2017. New patients diagnosed in men with BPH and taking medications that contained either 5ARI or AB between July 1, 2013, and June 30, 2015, were included (n = 1,461 5ARI; n = 18,650 AB). The primary outcome was depression defined per the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10: F32-34, F38, F412, F432). Logistic regression was used to implement 1:1 propensity score (PS) matching of patients taking 5ARI to those taking AB to adjust for confounding. Cox proportional hazard models were used to compare the risk of depression associated with 5ARI versus AB.ResultsBalance in baseline characteristics between the treatment groups were achieved within PS matched pairs (1,461 pairs). Compared to the AB medication group, the 5ARI group had lower depression (HR: 0.69, 95% CI: [0.51–0.92]). However, we could not find a clinically relevant, statistical difference after PS matching (HR: 0.91, 95% CI: [0.61–1.36]).ConclusionsThe risk of depression associated with 5ARI was not meaningfully different from AB in Korea, which suggests that medical officials should provide the most appropriate medication for BPH patients by considering both treatment benefits and depression risk.

Sexual, physical, and overall adverse effects in patients treated with 5α-reductase inhibitors: a systematic review and meta-analysis.

Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64–2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74–2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80–2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.

5α-Reductase Inhibitors Are Associated with Reduced Risk of SARS-CoV-2 Infection: A Matched-Pair, Registry-Based Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a disproportionately severe effect on men, suggesting that the androgen pathway plays a role in the disease. Studies on the effect of castration and androgen receptor blockade have been mixed, while 5α-reductase inhibitor (5ARI) use in men with COVID-19 (2019 novel coronavirus) have shown potential benefits. We assessed the association of 5ARI use on risk of community acquired SARS-CoV-2 infection. A total of 60,474 males in a prospective registry of people tested for SARS-CoV-2 between March 8, 2020 and February 15, 2021 were included. Using a matched cohort design, men using 5ARIs were matched 1:1 to non5ARI users. Independent analysis using unconditional multivariable logistic regression on the entire unmatched data set was completed for validation. Primary outcome measures were the association of 5ARI use on rates of SARS-Cov-2 positivity and disease severity. Of the men 1,079 (1.8%) reported 5ARI use and 55,100 were available for matching. The final matched cohorts included 944 men each. Mean duration of use was 60.4 months (IQR 17-84 months). Absolute risk for infection was significantly lower in 5ARI users compared to nonusers, 42.3% (399/944) vs 47.2% (446/944), respectively (absolute risk reduction [ARR] 4.9%, OR 0.81, 95% CI 0.67-0.97, p=0.026). Unconditional multivariable logistic regression analysis of the entire study cohort of 55,100 men confirmed the protective association of 5ARI use (ARR 5.3%, OR=0.877, 95% CI 0.774-0.995, p=0.042). Use of 5ARIs was not associated with disease severity. Use of 5ARIs in men without prostate cancer was associated with a reduction in community acquired SARS-CoV-2 infection.

Restorative effects of red onion (Allium cepa L.) juice on erectile function after-treatment with 5α-reductase inhibitor in rats.

Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions among aged men. The use of 5α-reductase inhibitors (5-ARIs) to treat BPH was linked to erectile dysfunction (ED). Many medicinal plants and secondary metabolites are used in the management of ED. Onion (Allium cepa L.) is an economically affordable vegetable with vital phytochemicals and biological functions. The study aimed to identify the beneficial effects of onion juice on dutasteride (a 5-ARI)-induced ED. Rats were divided into two groups (n = 5 per group): control and dutasteride-treated rats (0.5 mg/kg/day). Dutasteride was administered in drinking water for 12 weeks. Experiments were performed at the end of the 12th week. In vivo erectile responses were measured before and after intracavernosal injection of onion. Relaxant responses to onion juice were examined in the corpus cavernosum (CC). Acetylcholine (ACh)-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)-induced relaxation responses in CC tissues were evaluated in the absence and presence of onion juice. Total intracavernosal pressure (ICP) and ICP/ mean arterial pressure were significantly reduced in dutasteride-treated rats (1881.14 ± 249.72 mmHg, P < 0.001;0.26 ± 0.03, P < 0.01) as compared to control rats (4542.60 ± 429.19 mmHg, 0.51 ± 0.05), which was normalized after the intracavernous administration of onion (3288.60 ± 185.45 mmHg, 0.58 ± 0.04). Onion markedly induced relaxant responses in control (72.5 ± 4.7) and dutasteride-treated (66.5 ± 2.7) groups after precontraction with phenylephrine. Relaxation responses to onion were partially inhibited after precontraction with KCl (32.5 ± 3.1, P < 0.001). The relaxant responses to ACh (14.9 ± 4.2, P < 0.01) were diminished in dutasteride-treated CC) compared to control CC(59.8 ± 3.4), which was enhanced after the incubation with onion (36.6 ± 4.8). There were no differences in relaxation response to SNP among all groups. However, relaxation response to SNP was reduced in dutasteride-treated CC at 1 μM(P < 0.05) and 10 μM dosages (P < 0.001), which was partially increased after the incubation with onion at 10 μM dosage (P < 0.01). The presence of onion did not change the reduction in EFS-caused relaxation in the dutasteride-treated group. The current data suggest that red onion juice has a restorative effect on erectile function and endothelium-dependent relaxation response following the treatment of dutasteride.

The Use of 5-Alpha Reductase Inhibitors and Alpha-1 Blockers Does Not Improve Clinical Outcome in Male Patients Undergoing Radical Cystectomy for Bladder Cancer in Quebec, Canada.

Existing literature suggests that bladder cancer (BC) outcome may be improved when patients use 5α-reductase inhibitors and/or α1-blockers, but such a conclusion may be subject to publication bias. We evaluated whether preoperative use of 5α-reductase inhibitors or α1-blockers was associated with improved clinical outcomes in a cohort of patients with BC undergoing radical cystectomy (RC). Using provincial health administrative databases, we retrospectively identified male BC patients undergoing RC in Quebec province between 2000 and 2015, and we collected data from 2 years before RC until December 2016 or death. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, propensity score matching, and uni- and multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, annual RC volume of each hospital and surgeon, neoadjuvant chemotherapy use, and type of bladder diversion. Of the 2822 patients included, 284 patients used 5α-reductase inhibitors and 1001 patients used α1-blockers prior to surgery. Median follow-up time was 7.7 years. Patients who used 5α-reductase inhibitors or α1-blockers were generally older, had more comorbidities, and were treated more recently in academic centers. Overall, bladder cancer-specific and recurrence-free survival did not differ significantly between those using 5α-reductase inhibitors prior to surgery and controls who never used 5α-reductase inhibitors. Adjusted hazard ratios were 1.03 (95% confidence interval [CI], 0.88-1.21) for overall survival, 1.12 (95% CI, 0.92-1.36) for bladder cancer-specific survival, and 1.19 (95% CI, 0.99-1.42) for recurrence-free survival. The aforementioned outcomes were significantly worse in patients who used α1-blockers prior to surgery compared to controls, with respective adjusted hazard ratios of 1.15 (95% CI, 1.04-1.27), 1.19 (95% CI, 1.05-1.35), and 1.18 (95% CI, 1.05-1.33). Preoperative use of 5α-reductase inhibitors and α1-blockers did not improve clinical outcome in our cohort of male patients undergoing radical cystectomy for bladder cancer.

Estimating acute urinary retention risk post prostate high dose-rate (HDR) brachytherapy: A clinical-based recursive partitioning analysis

PurposeTo determine factors associated with need for post-procedural catheterization in prostate cancer patients treated with 15 Gy high dose-rate brachytherapy boost (HDR-BT). Material and methodsPatients treated with 15 Gy HDR-BT followed by EBRT were retrospectively evaluated for development of urinary retention and hematuria requiring catheterization in the first 30 days post procedure. Clinical characteristics and treatment details were obtained and used as independent variables under study. Univariable and multivariable logistic regression analysis were used to determine predictors of post brachytherapy complications and a classification tree for risk of urinary retention was created using recursive partitioning analysis (RPA). ResultsA total of 425 patients treated with 15 Gy HDR-BT were included in this analysis. 27 patients (6.3%) required catheter placement due to acute urinary retention and thirteen other patients (3%) developed hematuria requiring urinary catheter insertion ± continuous bladder irrigation. Number of needles, prostate volume and prior use of ADT, alpha-blockers or 5α-reductase inhibitors were statistically associated with urinary retention in the univariable logistic regression analysis. In multivariable analysis, prostate volume, previous use of alpha-blocker, and use of ADT remained significant. In the RPA, populations were identified in which the rate of urinary retention ranged from 2% to 50% depending on presence of one or more of these risk factors. ConclusionThe overall rate of acute urinary complications post HDR brachytherapy is low, but the individual risk of urinary retention can increase depending on the number of risk factors present. A more patient-directed retention risk estimation can be performed by using the classification risk tree presented here.

The Association of 5α-Reductase Inhibitor With Suicidality

Using a large nationwide cohort, this study aimed to determine the risk of suicide after the use of a 5α-reductase inhibitor, an antiandrogenic medication commonly used in the treatment of lower urinary tract symptoms. A retrospective population-based cohort study was performed using the Korean National Health Insurance Service database. The study consisted of 51,466 men 60 years or older who underwent health examinations between 2005 and 2006. Individuals using a 5α-reductase inhibitor were compared with nonusers based on drug exposure between 2003 and 2006. Individuals using a 5α-reductase inhibitor were additionally divided into tertiles based on cumulative 5α-reductase inhibitor exposure. The incidence of completed suicide was documented during 7 years of follow-up, starting January 1, 2007. No significant risk of suicide was observed among 5α-reductase inhibitor users compared with 5α-reductase inhibitor nonusers (hazard ratio = 1.02, 95% confidence interval = 0.70-1.48). Cumulative 5α-reductase inhibitor exposure was also not associated with increased risk of suicide (p for trend = .543). 5α-Reductase inhibitor use was not associated with an elevated risk of suicide during a long-term follow-up period. A limitation of this study is that possible drug exposure after the index date was not accounted for. Although 5α-reductase inhibitor may increase the risk of depressive symptoms, the present data indicate that the drug is safe in terms of long-term suicide risk.

Post-finasteride syndrome

Finasteride is a 5α-reductase enzyme inhibitor that has been approved for the treatment of male androgenic alopecia since 1997. Over time, it has been considered a safe and well-tolerated drug with rare and reversible side effects. Recently there have been reports of adverse drug-related reactions that persisted for at least three months after discontinuation of this drug, and the term post-finasteride syndrome arose. It includes persistent sexual, neuropsychiatric, and physical symptoms. Studies to date cannot refute or confirm this syndrome as a nosological entity. If it actually exists, it seems to occur in susceptible people, even if exposed to small doses and for short periods, and symptoms may persist for long periods. Based on currently available data, the use of 5α-reductase inhibitors in patients with a history of depression, sexual dysfunction, or infertility should be carefully and individually assessed.

A numerical simulation study of the dual role of [formula omitted]-reductase inhibitors on tumor growth in prostates enlarged by benign prostatic hyperplasia via stress relaxation and apoptosis upregulation

5α-reductase inhibitors are regarded as a promising chemoprevention strategy to reduce the incidence and delay the progression of prostate cancer. Landmark clinical trials have shown the chemopreventive potential of these drugs, but they appear to be mostly effective in mild tumors and have also been correlated with a higher prevalence of advanced prostate cancer. Hence, the use of 5α-reductase inhibitors for prostate cancer chemoprevention has become a controversial issue. The effects of these drugs on prostate cancer growth remain incompletely understood, but they are thought to promote apoptosis in the tumor. Additionally, 5α-reductase inhibitors induce global prostate shrinkage, which decreases the tumor-inhibiting effect of the mechanical stress accumulated in prostatic tissue due to common prostate enlargement with age. Thus, the competition between this mechanical effect and apoptotic upregulation may explain the controversial outcomes of 5α-reductase inhibitors on prostate cancer. Here, we extend our mechanically-coupled model of prostate cancer growth by including the mechanical and apoptotic action of 5α-reductase inhibitors and explore their combined effect on an aggressive tumor in silico. Our simulations show that the apoptotic boost dominates in the first months of therapy but the long-term outcome of 5α-reductase inhibitors depends on its competition with a decrease in hydrostatic stress caused by prostate shrinkage, which favors tumor growth. By combining moderate or strong prostate shrinkage with mild or intense apoptotic upregulation, our simulations show different tumor growth dynamics ranging from long-term inhibition of prostate cancer growth to rapidly growing large tumors, which may evolve towards advanced disease. Thus, our proposed mechanism for the action of 5α-reductase inhibitors may contribute to resolve the controversy around the use of these drugs for chemoprevention and to gain insight on prostate cancer dynamics during its use. The computational technology used herein could also assist physicians to monitor prostatic tumors during 5α-reductase inhibitor therapy and enable the early identification of responders from non-responders in a patient-specific manner.

Effect of 5α-reductase inhibitors on the efficiency of thulium:yttrium-aluminium-garnet (RevoLix®) vaporesection for treating benign prostatic hyperplasia.

PurposePreoperative use of 5α-reductase inhibitors (5ARIs) may cause fibrosis of the prostate tissue and reduce the efficiency of thulium laser surgery for treating benign prostate hyperplasia (BPH). Thus, we investigated the effects of preoperative 5ARI use in this setting.Materials and MethodsThis retrospective study examined 184 patients who underwent thulium laser surgery for BPH during 2012–2017. Patients were grouped according to their 5ARI use in order to compare their preoperative and intraoperative characteristics and subsequent outcomes. Surgical efficiency was assessed using vaporesection efficiency. The total operation time, vaporesection time and prostate volume change were measured.ResultsThe 5ARI+ group included 83 patients (45.1%) and the 5ARI− group included 101 patients (54.9%). There were no significant differences in the two groups' preoperative characteristics, postoperative prostate size, thulium laser energy use, or prostate volume reduction rate. However, relative to the 5ARI− group, the 5ARI+ group had a significant shorter total operative time (65.0 min vs. 70.0 min, p=0.013) and a significantly shorter vaporesection time (48.0 min vs. 54.0 min, p=0.014), which resulted in significantly higher vaporesection efficiency in the 5ARI+ group (0.66 mL/min vs. 0.51 mL/min, p<0.001). Both groups exhibit significant improvements in their quality of life score and International Prostate Symptom Score during the 12-month follow-up.ConclusionsIn contrast with our expectations, the preoperative use of 5ARI increased the efficiency of thulium laser surgery for BPH. Thus, it may not be necessary to stop 5ARI treatment before performing thulium laser surgery in this setting.

Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults

This cohort study examines the association between use of 5α-reductase inhibitors and prostate cancer mortality among US Medicare beneficiaries.

Reproductive endocrinologists are the gatekeepers for male infertility care in North America: results of a North American survey on the referral patterns and characteristics of men presenting to male infertility specialists for infertility investigations

To characterize the referral patterns and characteristics of men presenting for infertility evaluation using data obtained from the Andrology Research Consortium. Standardized male infertility questionnaire. Male infertility centers. Men presenting for fertility evaluation. Not applicable. Demographic, infertility history, and referral data. The questionnaires were completed by 4,287 men, with a mean male age of 40years ± 7.4years and female partners age of 37years ± 4.9years. Most were Caucasian (54%) with other races being less commonly represented (Asian 18.6%, and African American 5.5%). The majority (59.7%) were referred by a reproductive gynecologist, 19.4% were referred by their primary care physician, 4.2% were self-referred, and 621 (14.5%) were referred by "other." Before the male infertility investigation, 12.1% of couples had undergone intrauterine insemination, and 4.9% of couples had undergone invitro fertilization (up to six cycles). Among the male participants, 0.9% reported using finasteride (5α-reductase inhibitor) at a dose used for androgenic alopecia, and 1.6% reported exogenous testosterone use. This broad North American patient survey shows that reproductive gynecologists are the de facto gateway for most male infertility referrals, with most men being assessed in the male infertility service being referred by reproductive endocrinologists. Some of the couples with apparent male factor infertility are treated with assisted reproductive technologies before a male factor investigation. The survey also identified potentially reversible causes for the male infertility including lifestyle factors such as testosterone and 5α-reductase inhibitor use.

Accuracy of the preoperative PSA level for predicting clinically significant incidental transitional zone-prostate cancer before endoscopic enucleation of very large adenoma.

To analyse the accuracy of high preoperative PSA levels for predicting transitional zone incidental PCa (TZ-PCa) in men with very large prostates. Perioperative data from 375 consecutive patients who underwent endoscopic enucleation of the prostate (EEP) for benign prostatic obstruction between July 2013 and December 2018 were retrospectively reviewed. Patients were stratified into three groups according to the preoperative PSA level: low-PSA (< 4ng/mL), intermediate-PSA (4 ≤ PSA < 10ng/mL) and high-PSA (≥ 10ng/mL). Men in each group were propensity score matched by age, 5α-reductase inhibitor (5-ARI) use, prostate volume and mpMRI. The TZ-PCa incidence rate was retrospectively compared by preoperative PSA level in a propensity score model including all predetermined variables. Age, prostate volume, 5-ARI use were similar between patient groups. The median PSA levels in the low-, intermediate- and high-PSA groups were 3 [2.3; 3.4], 6.6 [5.3; 8.1] and 12.7 [11; 16.7] ng/mL, respectively. The median prostate volume was > 100 grams in all groups (108, 105 and 120cc, respectively). The T1a-Gleason 6 incidental TZ-PCa rate was statistically comparable between the three groups (3.4, 5.1 and 8.6% in the low-, intermediate- and high-PSA groups, respectively). The detection rate of clinically significant TZ-PCa was low for preoperative PSA levels > 4ng/mL (1.7%); with no difference between the intermediate- and high-PSA groups. In men with large glands, the clinically significant incidental TZ-PCa detection rate was similar regardless of the preoperative PSA level stratum. Such details may help with patient counselling during BPH surgical management.

Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies.

To provide dermatologists and oncologists with a foundation for practical understanding and uses of 5α-reductase inhibitors and spironolactone for breast cancer patients and survivors receiving endocrine therapies (ETs), including the effect of these treatments on sex hormone levels, any reported drug interactions, and any risk of malignancy. All published studies from January 1978 through April 2018 were considered, using databases such as PubMed, Google Scholar, and Science Direct. Forty-seven studies were included in this review. There is no evidence of interactions between 5α-reductase inhibitors and spironolactone with ETs used in breast cancer. Sex hormone alteration with 5α-reductase inhibitor or spironolactone use is variable. Three randomized controlled trials, 1 case-control study, and 6 retrospective cohort studies, including 284 female patients, studied the effects of5α-reductase inhibitors on serum estrogen levels. Levels were increased in 97 of 284 (34%) patients, decreased in 15 of 284 (5.3%) patients, and unchanged in 162 of 284 (57%) patients. Four retrospective cohort studies, 1 case study, and 1 double-blinded crossover study, including 95 female patients, assessed the effectofspironolactone on estrogen levels. Levels were increased in 25 of 95 (26%) patients, decreased in 6 of 95 (6.3%) patients, and unchanged in 64 of 95 (67%) patients. Ultimately, most patients did not have a significant alteration in the level of estrogen when using 5α-reductase inhibitors or spironolactone. No consistent evidence of increased risk of female breast cancer while on spironolactone was reported in 3 studies including 49,298 patients; the risk of breast cancer with the use of 5α-reductase inhibitors has not been studied. Most patients did not show increased estrogen levels with spironolactone and there were no data suggesting increased risk of breast cancer. Based on hormonal and pharmacological activity, spironolactone may be considered for further research on alopecia and hirsutism in breast cancer patients.