5α-reductase Inhibitors Research Articles

Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality

There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM). To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa. This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021. After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190). Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM. The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively). The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.

A PROSPECTIVE OBSERVATIONAL STUDY TO EVALUATE THEPRESCRIBING PATTERN AND TO ASSESS THE THERAPEUTIC OUTCOME IN THE MANAGEMENT OF BENIGN PROSTATE HYPERPLASIA USING INTERNATIONAL PROSTATE SYMPTOMSCORE

Background The present study aimed to evaluate the prescribing pattern and to assess the therapeutic outcome in the management of Benign Prostatic hyperplasia using IPSS and to provide a best treatment option for management of BPH. Methodology It is prospective observational study, 80 patients ≥50 years with BPH and treated with alpha- 1 blockers and 5-alpha reductase inhibitors were included in our study. The materials we used in our study include Informed consent form, Patient data collection form, and International Prostate Symptom Score. Results In IPSS follow up, we got mean baseline IPSS as 13.18 out of 35 and the mean follow up IPSS as 5.18. It shows that there is significant reduction of symptoms. We got mean difference of monotherapy and combination therapy as 7 and 8. Results with p<0.05 were considered as significant. Conclusion The therapeutic outcomes in evaluating treatment benefits in patients with LUTS/BPH were improvement in subjective symptoms and quality of life. Long term adherence to the medications resulted in decrease in bothersome LUTS. Based on mean difference obtained in our results, we conclude that combination therapy is bit more effective than monotherapy

Possible role of 5-alpha reductase inhibitors in non-invasive bladder urothelial neoplasm: multicenter study.

About 75% of urothelial bladder cancers are non-muscle invasive (NMIBC), and limited to mucosa (Ta or CIS) or sub-mucosa (T1). An increase of androgen expression and androgen receptors has a positive effect on oncogenic expression. We aimed to evaluate whether 5-alpha reductase inhibitors (5-ARI) have a role in NMIBC. We retrospectively evaluated the clinical and pathological data of 423 patients with NMIBC who underwent transurethral bladder resection. We considered the number of resections, number of total recurrences, time of recurrences, and histopathology details. The population was classified into two groups: treated and untreated with 5-ARIs. The enrolled patients were in treatment with 5ARIs for symptomatic prostatic hyperplasia for at least 12 months. Mean follow-up time was 30.43 months. Patients treated with 5-ARIs had a lower rate of recurrence (14%) than the untreated group (37%). There was a significant difference in the mean number of recurrences between the untreated and the treated group (P=0.006). Furthermore, the treated group showed a significantly greater number of low than high grade tumors, compared to the untreated group (P≤0.05). There was a significant decrease in the number of muscle invasive tumors in treated patients (P=0.032). The recurrence-free survival rate of patients treated with 5-ARIs was significantly higher (P=0.0001). Long-term treatment with 5-ARIs might reduce the risk of bladder tumor recurrence, extension of lesions and increase the recurrence-free survival rate. A long-term, randomized prospective study could definitively assess the possible role of these drugs.

Benign Prostatic Hyperplasia (BPH): A Comprehensive Analysis of the Malaise and Summarizing Possible Management Options through Phytotherapeutic Agents

Benign prostatic hyperplasia (BPH) is a severe illness affecting middle-aged and geriatric male patients. This disease normally occurs at the age of 40 or above and is also associated with sexual dysfunction. Alpha-blockers and 5α-reductase inhibitors are the preferred drugs practiced to treat BPH. However, invasive surgical therapy remains the gold standard for managing the condition in the case of refractory and intricate BPH conditions. Due to the fear of sexual dysfunction and the detrimental influence on their quality of life, most patients seek to avoid synthetic drugs and surgery. For this reason, several patients turn to phytotherapy and other alternative therapies. The authors looked at the existing perceptions of epidemiology, etiology, and pathophysiology associated with BPH in this review article. In addition, this article contained basic information on the pathological roles of inflammation in BPH and various diagnoses and treatment options. It was well reported that the administration of medicinal herbs played a vital role in managing BPH. In recent years, many researchers worldwide have reported the efficiency and safety of phytochemicals in managing numerous pathological disorders in-vivo and in-vitro conditions and the prevention of illness.

Pharmacovigilance analysis of reports of sexual dysfunction associated with finasteride use: Implications for the post-finasteride syndrome

ABSTRACT Introduction Finasteride, a 5α-reductase inhibitor, is used in the management of androgenetic alopecia and benign prostatic hyperplasia (BPH). There is growing attention to the post-finasteride syndrome, a constellation of adverse events associated with finasteride use which include sexual dysfunction. Objective To investigate reports of sexual dysfunction associated with finasteride. Methods We conducted a pharmacovigilance study using VigiBase, the World Health Organization's international database of individual case safety reports. We used the reporting odds ratio (ROR). Sensitivity analyses stratified by indication (BPH and alopecia) and age (<45 and ≥45); compared finasteride signals to those of drugs with different mechanisms but similar indications (minoxidil for alopecia and tamsulosin for BPH); compared finasteride to a drug with a similar mechanism of action (dutasteride); and compared reports of sexual dysfunction before and after 2012. Results We identified 7700 sexual dysfunction reports associated with finasteride. There was a disproportionality signal for sexual dysfunction associated with finasteride (ROR 50.3, 95% confidence interval (CI) 49.0-51.6). Patients under 45 (ROR 56.4, 95% CI 53.1-59.9) and alopecia patients (ROR 64.9, 95% CI 62.7-67.2) drove the signal. All sensitivity analyses met the threshold of signal significance. Results of primary analyses are presented in Tables 1. Conclusions We detected disproportional signals of sexual dysfunction linked with finasteride use. Despite sexual dysfunction being more prevalent in older BPH patients, we detected larger signals of sexual dysfunction in young alopecia patients. Sensitivity analyses suggest that reports of sexual dysfunction linked with finasteride use may be confounded by indication and by stimulated reporting. However, confounding alone is unlikely to account for the totality of the signal observed in young patients with alopecia. Disclosure Work supported by industry: no. A consultant, employee (part time or full time) or shareholder is among the authors (QDT reports personal fees from Astellas, Bayer, Janssen, Insightec, and Intuitive Surgical, outside the submitted work. NB, DSE, and KCZ reports consulting fees from Procept Robotics, Olympus, and BSC. BC reports consulting fees from BSC, Olympus, Meditate, Ferring, and Urovant.).

Presence of Codes for Indication for Use in Clinical Practice Research Datalink Aurum: An Assessment of Benign Prostatic Hyperplasia Treatments.

BackgroundAssessments of strengths and limitations of new data sources are critical for making decisions about suitability for specific research questions. For some studies, it is necessary to capture a drug’s indication for use.ObjectiveTo assess the presence of indications for prescription use in Clinical Practice Research Datalink (CPRD) Aurum (January 1988–June 2021) by describing the proportion of men in CPRD Aurum who had a recorded indication for use of prescriptions for 5-alpha reductase inhibitors (5-ARI), alpha blockers (AB), or tadalafil, which have multiple indications.MethodsFrom a random sample of 154 practices of CPRD Aurum data, we selected 85,597 male patients with a prescription for a 5-ARI, an AB, or tadalafil. Among these patients, we described presence of codes indicating whether the patient had benign prostatic hyperplasia, hypertension, erectile dysfunction, or alopecia using three indication definitions: narrow (specific diagnoses recorded within one year before and up to 90 days after the prescription), broad (specific diagnoses or supporting clinical codes in the time period described above), and widest (diagnoses or supporting codes recorded at any time before the prescription and up to 90 days after the prescription).ResultsUsing the narrow indication definition limited to diagnoses only, 39,861 (46.6%) patients’ records contained an indication for use. The broad definitions, which additionally included supporting codes, captured indications for 62,912 (73.5%) patients and the widest definition, which additionally included supporting codes and all available data before the first prescription date, captured indications for 71,478 (83.5%) patients. Indications were present more often for prescriptions in 2005 and later (85.9%).ConclusionThe findings of this assessment suggest that CPRD Aurum can be used for studies that require information on treatment indications for BPH and potentially for treatments of other chronic diseases managed in the primary care setting.

Isolation and HPLC Quantitative Determination of 5α-Reductase Inhibitors from Tectona grandis L.f. Leaf Extract.

Steroid 5α-reductase plays a crucial role in catalyzing the conversion of testosterone to dihydrotestosterone, which is involved in many androgen-dependent disorders. Leaf-hexane extract from Tectona grandis L.f. has shown promise as a 5α-reductase inhibitor. The objectives of this current study were to isolate and identify 5α-reductase inhibitors from T. grandis leaves and to use them as the bioactive markers for standardization of the extract. Three terpenoid compounds, (+)-eperua-8,13-dien-15-oic acid (1), (+)-eperua-7,13-dien-15-oic acid (2), and lupeol (3), were isolated and evaluated for 5α-reductase inhibitory activity. Compounds 1 and 2 exhibited potent 5α-reductase inhibitory activity, while 3 showed weak inhibitory activity. An HPLC method for the quantitative determination of the two potent inhibitors (1 and 2), applicable for quality control of T. grandis leaf extracts, was also developed. The ethanolic extract showed a significantly higher content of 1 and 2 than found in the hexane extract, suggesting that ethanol is a preferable extraction solvent. This study is the first reported isolation of 5α-reductase inhibitors (1 and 2) from T. grandis leaves. The extraction and quality control methods that are safe and useful for further development of T. grandis leaf extract as an active ingredient for hair loss treatment products are also reported.

Naftopidil enantiomers suppress androgen accumulation and induce cell apoptosis via the UDP-glucuronosyltransferase 2B15 in benign prostate hyperplasia

Accumulation of androgens mediate alterations in prostate growth and has emerged as an essential factor in benign prostate hyperplasia (BPH). Dihydrotestosterone (DHT), the most potent natural androgen, binds to androgen receptors (AR) and regulates the prostate growth. Many inhibitors of DHT synthesis have been developed to reduce DHT levels and used in the treatment of prostate diseases. However, therapies targeting the elimination of the DHT remain limited. The DHT in prostate is metabolized by UDP-glucuronosyltransferase 2B (UGT2B) and transforms into inactive products. In this study, we analyzed and demonstrated that two enantiomers of naftopidil (NAF), an α1D/1A-adrenoceptor blocker, induced expression and activity of UGT2B in BPH rat prostate models as well as UGT2B15 in human prostate cells, BPH-1. The NAF enantiomers reduced intraprostatic and intracellular DHT levels, thus promoting cell apoptosis. Besides, assays with siRNA UGT2B15 transfection showed that UGT2B15 played an essential role in mediating the effects of the NAF enantiomers. The UGT2B15 mediated the inhibition of AR and PSA expression by NAF enantiomers. The data showed that the mechanism of upregulating UGT2B15 by the NAF enantiomers might differ from that of AR antagonists and 5α-reductase inhibitors. Together, our results demonstrated that NAF enantiomers could be potential and novel UGT2B15 regulators, which accelerated the DHT elimination and promoted apoptosis of BPH-1 cells. This study could help expand the clinical application of NAF and support the development of new therapeutic strategies targeting the elimination of androgens for the treatment of BPH and other androgen-sensitive diseases.

Pharmacovigilance Analysis of Reports of Sexual Dysfunction Associated with Finasteride Use: Implications for the Post-Finasteride Syndrome

ABSTRACT Introduction Finasteride, a 5α-reductase inhibitor, is used in the management of androgenetic alopecia and benign prostatic hyperplasia (BPH). There is growing attention to the post-finasteride syndrome, a constellation of adverse events associated with finasteride use which include sexual dysfunction. Objective To investigate reports of sexual dysfunction associated with finasteride. Methods We conducted a pharmacovigilance study using VigiBase, the World Health Organization's international database of individual case safety reports. We used the reporting odds ratio (ROR). Sensitivity analyses stratified by indication (BPH and alopecia) and age (<45 and ≥45); compared finasteride signals to those of drugs with different mechanisms but similar indications (minoxidil for alopecia and tamsulosin for BPH); compared finasteride to a drug with a similar mechanism of action (dutasteride); and compared reports of sexual dysfunction before and after 2012. Results We identified 7700 sexual dysfunction reports associated with finasteride. There was a disproportionality signal for sexual dysfunction associated with finasteride (ROR 50.3, 95% confidence interval (CI) 49.0-51.6). Patients under 45 (ROR 56.4, 95% CI 53.1-59.9) and alopecia patients (ROR 64.9, 95% CI 62.7-67.2) drove the signal. All sensitivity analyses met the threshold of signal significance. Results of primary and sensitivity analyses are presented in Tables 1 and 2. Conclusions We detected disproportional signals of sexual dysfunction linked with finasteride use. Despite sexual dysfunction being more prevalent in older BPH patients, we detected larger signals of sexual dysfunction in young alopecia patients. Sensitivity analyses suggest that reports of sexual dysfunction linked with finasteride use may be confounded by indication and by stimulated reporting. However, confounding alone is unlikely to account for the totality of the signal observed in young patients with alopecia. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: QDT reports personal fees from Astellas, Bayer, Janssen, Insightec, and Intuitive Surgical, outside the submitted work. NB, DSE, and KCZ reports consulting fees from Procept Robotics, Olympus, and BSC. BC reports consulting fees from BSC, Olympus, Meditate, Ferring, and Urovant.

Target Specific Uptake of a Newly Synthesized Radiolabeled 5α-Reductase Inhibitor "Tc-99m-17-Oxo-17a-Aza-D-Homo-5-Androsten-3β-yl Phenoxyacetate (Tc-99m-17a-Aza Steroid)" in Rat Prostatic Neoplastic Lesions.

Objective:Considering the 5α-reductase (5AR) inhibitory activity of the oximes and the importance of the ester group in increasing the anti-androgenic property, we reasoned to synthesize a compound having a lactam group in ring D and an ester group at the 3 β position of the androsterone nucleus. The study aims to radiolabel 17-oxo-17a-aza-D-homo-5-androsten-3β-yl phenoxyacetate (17a-aza steroid) with Tc-99m to evaluate its targeted uptake in experimentally induced prostate carcinogenesis in rats.Materials and Methods:The prediction of the optimal interaction and binding affinity of Tc-99m-17-oxo-17a-aza-D-homo-5-androsten-3 β-ylphenoxyacetate (Tc-99m-17a-aza steroid) toward 5AR inhibitor was done using Biopredicta Vlife MDS tool. Tc-99m-17a-aza steroid was developed by direct radiolabeling protocol. The radio-pharmacological characteristics (serum stability, plasma protein-binding ability, and lipophilicity) of the complex were evaluated. Further, the bio-distribution studies of the complex were performed in rats with experimentally induced prostate carcinogenesis.Results:The in-silico analysis exhibits favorable binding of Tc-99m-17a-aza toward 5AR with D score-130.97. The radiochemical purity of Tc-99m-17a-aza was 96.79%. The radio-complex maintained stability in the rat serum for a period of 6 h (hours). Plasma protein binding and Log Po/w value were observed to be 86.23 ± 7.08% and 0.118 ± 0.045, respectively. A significantly enhanced percent-specific uptake was observed in the prostate of rats with induced prostate carcinogenesis.Conclusion:The study concludes that Tc-99m-17a-aza exhibits prostate specificity and can be explored further for its potential as a radionuclide imaging probe.

Phytotherapy for male luts: What happens then? 10-year research

Introduction and objectivesOur objective is to assess the long-term results of phytotherapy, focusing on the interval between phytotherapy and pharmacological treatment and the predisposing risk factors to such switch on a 10-year follow-up. Material and methodsThe data of patients taking phytotherapy for mild to moderate male lower urinary tract symptoms (LUTS) from January to December 2010 were retrospectively reviewed from a prospectively maintained database. Patients were followed for 10 years through medical visits and telephone consultations. Results102 patients underwent at least one cycle of phytotherapy for LUTS. Twenty (19.6%) patients resolved their symptoms after one phytotherapy cycle and stopped any treatment, 27 (26.4%) continued phytotherapy, and 52 (51%) switched to alpha-blockers and/or 5a-reductase inhibitors after a median interval of 24 months. The reasons for treatment switch were symptoms (n = 45) or clinical progression (increased residual volume n = 15; urinary retention, n = 5). Patients switching to synthetic drugs had median higher age (60 vs 49), prostate volume (40 vs 26 cc), prostate specific antigen (PSA) (1.9 vs 0.9 ng/ml), residual volume (40 vs 0 cc), and a lower maximum flow rate (Qmax) (12 vs 15 ml/s) at presentation. Conclusions46% patients with mild to moderate LUTS undergoing phytotherapy will be either free of treatment or still on phytotherapy at 10 years from disease presentation. Older patients with larger prostates, increased residual volume and PSA, should be informed regarding their higher risk of symptomatic or clinical progression: the risk of a treatment switch to alpha-blockers or 5a-reductase inhibitors becomes an actual fact after an average span of 2 years.

Biochemical Characterization of the Pharmacological Effects of Yagari in Experimentally Induced Benign Prostatic Hyperplasia

AbstractBenign prostatic hyperplasia is a progressive pathologic condition common in ageing men, constituting a health burden. Benign prostatic hyperplasia is characterized by the proliferation of prostatic tissues, prostate enlargement, and lower urinary tract symptoms. The use of herbal medicine in the management and treatment of benign prostatic hyperplasia has shown some promise. The efficacy and potency of some polyherbal extracts have been scientifically proven in the management and treatment of diseases, while many others are yet to be investigated. The aim of this study was to determine the effect of the herbal mixture Yagari on experimentally induced benign prostatic hyperplasia in rats and to identify its pharmacologically active agents. The effect of the herbal mixture on experimentally induced benign prostatic hyperplasia in rats was determined using 36 male Wistar rats grouped randomly into 6 groups of 6 rats each. The test rats were treated subcutaneously using a combination of dihydrotestosterone and estradiol valerate in a 10:1 ratio for 28 days according to the standard method. The test rats were thereafter treated with the herbal mixture for 21 days. Prostate-specific antigen, inflammatory cytokines, assay of prostate function hormonal and prostate function enzyme activities, and kidney function test were evaluated in the blood samples collected by ocular puncture applying standard methods. Prostates were harvested and examined for histopathological changes. Biological activity-guided fractionation of Yagari in a silica gel column was carried out and using phospholipase A2 activity as a biomarker. The identity of the bioactive compounds was determined using mass spectroscopy and nuclear magnetic resonance. The herbal mixture showed a positive effect on prostatic hyperplasia by decreasing urinary obstruction through the inhibition of 5-alpha reductase, anti-inflammatory activity, and decreased level of sex hormones. Characterization by spectral studies revealed apigenin (4´,5,7-trihydroxyflavone, molecular weight).

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.

Fitoterapia para los síntomas del tracto urinario inferior en el varón: ¿qué ocurre después? Diez años de investigación

Introduction and objectivesOur objective is to assess the long-term results of phytotherapy, focusing on the interval between phytotherapy and pharmacological treatment and the predisposing risk factors to such switch on a 10-year follow-up. Material and methodsThe data of patients taking phytotherapy for mild to moderate male lower urinary tract symptoms (LUTS) from January to December 2010 were retrospectively reviewed from a prospectively maintained database. Patients were followed for 10 years through medical visits and telephone consultations. Results102 patients underwent at least one cycle of phytotherapy for LUTS. Twenty (19.6%) patients resolved their symptoms after one phytotherapy cycle and stopped any treatment, 27 (26.4%) continued phytotherapy, and 52 (51%) switched to alpha-blockers and/or 5a-reductase inhibitors after a median interval of 24 months. The reasons for treatment switch were symptoms (n=45) or clinical progression (increased residual volume n=15; urinary retention, n=5). Patients switching to synthetic drugs had median higher age (60 vs 49), prostate volume (40 vs 26cc), prostate specific antigen (PSA) (1.9 vs 0.9ng/ml), residual volume (40 vs 0cc), and a lower maximum flow rate (Qmax) (12 vs 15ml/sec) at presentation. Conclusions46% patients with mild to moderate LUTS undergoing phytotherapy will be either free of treatment or still on phytotherapy at 10 years from disease presentation. Older patients with larger prostates, increased residual volume and PSA, should be informed regarding their higher risk of symptomatic or clinical progression: the risk of a treatment switch to alpha-blockers or 5a-reductase inhibitors becomes an actual fact after an average span of 2 years.

5-Alpha Reductase Inhibitors and Prostate Cancer Mortality among Men with Regular Access to Screening and Health Care.

How 5-alpha reductase inhibitor (5-ARI) use influences prostate cancer mortality is unclear. The objective of this study was to determine whether men taking 5-ARIs with regular health care access have increased prostate cancer mortality. We undertook two analyses in the Health Professionals Follow-up Study examining 5-ARI use, determined by biennial questionnaires, and prostate cancer. A cohort analysis followed 38,037 cancer-free men for prostate cancer incidence from 1996 through January 2017 and mortality through January 2019. A case-only analysis followed 4,383 men with localized/locally advanced prostate cancer for mortality over a similar period. HRs and 95% confidence intervals (CI) were calculated for prostate cancer incidence and mortality. Men using 5-ARIs underwent more PSA testing, prostate exams and biopsies. Over 20 years of follow-up, 509 men developed lethal disease (metastases or prostate cancer death). Among men initially free from prostate cancer, 5-ARI use was not associated with developing lethal disease [HR, 1.02; 95% confidence interval (CI), 0.71-1.46], but was associated with reduced rates of overall and localized disease (HR, 0.71; 0.60-0.83). Among men diagnosed with prostate cancer, there was no association between 5-ARI use and cancer-specific (HR, 0.78; 95% CI, 0.48-1.27) or overall survival (HR, 0.88; 95% CI, 0.72-1.07). Men using 5-ARIs were less likely to be diagnosed with low-risk prostate cancer, without increasing long-term risk of lethal prostate cancer or cancer-specific death after diagnosis. Our results provide evidence that 5-ARI use is safe with respect to prostate cancer mortality in the context of regular health care access. See related commentary by Hamilton, p. 1259.

Hexanic Extract of Serenoa repens (Permixon®): A Review in Symptomatic Benign Prostatic Hyperplasia

The hexanic extract (HE) of Serenoa repens (Permixon®) is indicated for the symptomatic treatment of benign prostatic hyperplasia (BPH). The drug is the n-hexane lipidosterolic extract of the American dwarf palm tree (also known as saw palmetto). The anti-inflammatory activity of HE S. repens has been demonstrated in vitro, in vivo and in men with prostatic inflammation. In randomized clinical trials, the efficacy of HE S. repens was similar to that of an α-blocker in terms of improving voiding and storage symptoms, increasing urinary flow rate and reducing prostate volume in men with BPH. HE S. repens was also as effective as 5α-reductase inhibitors and/or α-blockers at improving lower urinary tract symptoms (LUTS) and quality of life (QOL) in real-world observational studies. HE S. repens was generally well tolerated, with a lesser impact on male sexual function compared with other available therapies. Thus, HE S. repens is a useful option for the treatment of symptomatic BPH.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40266-022-00924-3.

Incidental Prostate Cancer from Prostate with Benign Biopsies: A Predictive and Survival Analysis from Cohort Study.

PurposeThis cohort was to evaluate incidental prostate cancer (iPCa) from men with preoperative benign biopsies and demonstrate their outcomes under different managements.Patients and MethodsBetween 2015 and 2017, we analyzed the risk factors having iPCa from surgical specimens from men provided with benign preoperative biopsies of their prostates. Furthermore, we compared the survival outcomes according to the different managements after iPCa was diagnosed. Receiver operating characteristic (ROC) curve was utilized to find the best thresholds. Univariable and multivariable nested logit regression were performed to estimate the effect size of different independent variables. Odds ratio (OR) was expressed with 95% confidence interval, and the alpha level was 5%.ResultsIn 295 men we enrolled, there were 57 (19%) men having iPCa from surgical specimens. In univariable logit regression, we found significant variables of age, PSA, prostatic volume, PSA velocity ≥ 0.75 ng/mL/year for 3 years, taking 5α reductase inhibitors, abnormal digital rectal examination, cores of biopsy and surgical methods. In multivariable model, PSA was the strongest variable predicting iPCa (OR 3.81 [2.04–7.07]; Wald: 17.75; p < 0.001). In ROC curve, the best threshold was 9.025 ng/mL (area under curve: 0.95; sensitivity: 0.947; specificity: 0.866). In Kaplan–Meier curve of 27.89-month follow-up, robot-assisted simple prostatectomy (RASP) can provide similar PSA progression-free period as robot-assisted radical prostatectomy (RARP) following transurethral surgeries in organ-confined cancer (Log rank test, p = 0.293), and both of them were better than external-beam radiation therapy (RT) following transurethral surgeries (Log rank test, p < 0.001).ConclusionPSA was the strongest variable to predict iPCa out of prostate with preoperative benign biopsies. RASP was parallel to RARP following transurethral surgeries in organ-confined cancer in the short term.

Impact of chronic exposure to 5-alpha reductase inhibitors on the risk of hospitalization for COVID-19: a case-control study in male population from two COVID-19 regional centers of Lombardy, Italy.

There are sex differences in vulnerability to Coronavirus disease 2019 (COVID-19). The coronavirus S protein mediates viral entry into target cells employing the host cellular serine protease TMPRSS2 for S-protein priming. The TMPRSS2 gene expression is responsive to androgen stimulation and it could partially explain sex differences. We hypothesized that men chronically exposed to 5-alpha reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) have a lower risk of hospitalization for COVID-19. This is a population-based case-control study on consecutive patients positive for SARS-CoV-2 virus who required hospitalization for COVID-19 (cases), age-matched to beneficiaries of the Lombardy Regional Health Service (controls). Data were collected by two high-volume COVID-19 regional centers of Lombardy (Italy). The primary outcome was to compare the prevalence of patients chronically exposed to 5ARIs, who required hospitalization for COVID-19, with the one of controls. Overall, 943 males were enrolled; 45 (4.77%) were exposed to 5ARI. COVID-19 patients aged >55 years under 5ARI treatment were significantly less than expected on the basis of the prevalence of 5ARI treatment among age-matched controls (5.57 vs. 8.14%; P=0.0083, 95% CI: 0.75-3.97%). This disproportion was higher for men aged >65 (7.14 vs. 12.31%; P=0.0001, 95% CI: 2.83-6.97%). Eighteen 5ARIs-patients died; the mean age of men who died was higher than those who did not: 75.98±9.29 vs. 64.78±13.57 (P<0.001). Cox-regression and multivariable models did not show correlation between 5ARIs exposure and protection against intensive care unit admission/death. Men exposed to 5ARIs might be less vulnerable to severe COVID-19, supporting its use in disease prophylaxis.

Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin

BACKGROUND:A set of enduring conditions have been reported in the literature involving persistent sexual dysfunction after discontinuation of serotonin reuptake inhibiting antidepressants, 5 alpha-reductase inhibitors and isotretinoin.OBJECTIVE:To develop diagnostic criteria for post-SSRI sexual dysfunction (PSSD), persistent genital arousal disorder (PGAD) following serotonin reuptake inhibitors, post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction (PRSD).METHODS:The original draft was designed using data from two published case series (Hogan et al., 2014 and Healy et al., 2018), which represent the largest public collections of data on these enduring conditions. It was further developed with the involvement of a multidisciplinary panel of experts.RESULTS:A set of criteria were agreed upon for each of the above conditions. Features of PSSD, PFS and PRSD commonly include decreased genital and orgasmic sensation, decreased sexual desire and erectile dysfunction. Ancillary non-sexual symptoms vary depending on the specific condition but can include emotional blunting and cognitive impairment. PGAD presents with an almost mirror image of unwanted sensations of genital arousal or irritability in the absence of sexual desire. A new term, post-SSRI asexuality, is introduced to describe a dampening of sexual interest and pleasure resulting from a pre-natal or pre-teen exposure to a serotonin reuptake inhibitor.CONCLUSIONS:These criteria will help in both clinical and research settings. As with all criteria, they will likely need modification in the light of developments.

Medical treatment of male lower urinary tract symptoms: what's new?

Decades after the introduction of 5α-reductase inhibitors and α1-adrenoceptor antagonists, new data of practical relevance related to their desired and adverse effects continues to emerge. Some of these novel findings are to be taken seriously but are insufficiently established, for instance associations between drug use and depression or dementia. Multiple combination treatments have been tested. While combination treatment was often statistically superior to monotherapy, the difference was mostly in the range of 1 IPSS point, which raises doubts on the clinical relevance of the findings at the group level. The new evidence enables further personalisation of the treatment of male lower urinary tract dysfunction, but also makes individual risk-benefit considerations more complex.