5α-reductase Inhibitors Research Articles

Design of Nanocrystalline Suspension of Dutasteride for Intramuscular Prolonged Delivery

The aim of the study is to formulate an injectable nanocrystalline suspension (NS) of dutasteride (DTS), a hydrophobic 5α-reductase inhibitor used to treat benign prostatic hyperplasia and scalp hair loss, for parenteral long-acting delivery. A DTS-loaded NS (DTS-NS, 40 mg/mL DTS) was prepared using a lab-scale bead-milling technique. The optimized DTS-NS prepared using Tween 80 (0.5% w/v) as a nano-suspending agent, was characterized as follows: rod/rectangular shape; particle size of 324 nm; zeta potential of −11 mV; and decreased drug crystallinity compared with intact drug powder. The DTS-NS exhibited a markedly protracted drug concentration-time profile following intramuscular injection, reaching a maximum concentration after 8.40 days, with an elimination half-life of 9.94 days in rats. Histopathological observations revealed a granulomatous inflammatory response at the injection site 7 days after intramuscular administration, which significantly subsided by day 14 and showed minimal inflammation by day 28. These findings suggest that the nanosuspension system is a promising approach for the sustained release parenteral DTS delivery, with a protracted pharmacokinetic profile and tolerable local inflammation.

Is There an Association between 5a Reductase Inhibitors and Metabolic Syndrome? A Narrative Review of the Literature.

Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms.

Dutasteride, a 5 alpha reductase inhibitor, could be associated with the exacerbation of inflammation in patients with benign prostatic hyperplasia.

α-1 blockers and dutasteride are widely used as agents to treat benign prostatic hyperplasia (BPH); the impact of these drugs on prostatic inflammation is still unclear. Herein, we investigated the impact of α-1 blockers and dutasteride treatment of BPH in terms of the degree of prostatic inflammation. Tissue specimens were obtained from 143 BPH patients who were administered α-1 blockers up until their operation. Thirty-three of the patients had also been treated with dutasteride before the procedure. The degree of prostatic inflammation was quantified histologically by the ratio of high endothelial venule (HEV)-like vessels. We divided this retrospective cohort into α-1 blocker monotherapy and combination therapy (α-1 blockers + dutasteride) groups and evaluated clinical parameters of the two groups in relation to the degree of chronic prostatic inflammation. At the same time, we assessed factors exacerbating chronic prostatic inflammation. Comparison of the monotherapy and combination therapy groups showed no significant differences in the parameters of the urodynamic study or degree of chronic prostatic inflammation, whereas the IPSS total score, voiding subscore, nocturia, intermittency, weak stream, and straining were significantly lower in the combination than the monotherapy group. The duration of α-1 blockers administration was not correlated with the ratio of HEV-like vessels, while that of dutasteride was strongly correlated (correlation coefficient = 0.595; p < 0.001). Multiple regression analysis demonstrated that the duration of dutasteride administration was a key factor exacerbating the degree of chronic prostatic inflammation. The present study showed that despite their ameliorating effect on prostatic hyperplasia, dutasteride contributed significantly to chronic prostatic inflammation.

Therapeutic Potential of 5α-Reductase Inhibitor 17-oxo-17a-aza-D-homo-5-androsten-3β-yl phenoxyacetate (17a-aza Steroid) in the Management of Prostate Cancer

Background: The present study highlights the comparative therapeutic efficacy of the newly synthesized drug 17-Oximino-5-androsten-3β-yl 4-aminobenzoate (17a-aza steroid) and finasteride for the treatment of experimentally induced prostate carcinogenesis in rats. Considering the inhibitory activity of the oximes to 5α-reductase and the role of the ester group in augmenting the anti- androgenic property, we decided to synthesize a compound with a lactam moiety in ring D and esters at 3β position of androsterone nucleus as a more potent 5α-reductase inhibitor. Methods: In this study, 30 rats were divided into six groups, viz. Group I as normal controls, Group II was treated with carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (TP) for inducing prostate cancer, Group III rats were treated with finasteride (10mg/Kg of body weight for 8 weeks through gavage), Group IV was treated with 17a-aza steroid (10mg/Kg of body weight for 8 weeks through gavage), whereas, Group V and Group VI were given finasteride and 17a-aza steroid, respectively, with similar doses as in Group III and IV after pretreatment with a carcinogen (MNU) and hormone (TP). Results: The induction of carcinogenesis by treating animals with MNU+TP revealed a significant reduction in weight loss as compared to the normal control group, which, however, increased following 17a-aza steroid treatment. Furthermore, the study witnessed a significant improvement in prostatic biomarker, viz prostatic acid phosphatase (PAcP) in serum following finasteride and 17a-aza steroid treatment to MNU+TP treated rats. Histological investigation of prostate tissue sections of 17aaza steroid-treated prostate cancer rats showed milder hyperplastic glandular epithelium and exhibited signs of recovery as compared to carcinogen-treated rats. Conclusion: The present findings are preliminary and suggest that the 17a-aza steroid has therapeutic efficacy for the management of experimentally induced prostate cancer, as evidenced by changes in prostate weight, PAcP levels, and histology. In comparison to finasteride, further exploration is needed to assertively conclude its comparative therapeutic efficacy.

5α-reductase inhibitor exposure for dermatologic conditions does not increase the risk of female breast or gynecologic cancers: A population-based propensity score-matched cohort study

5α-reductase inhibitor exposure for dermatologic conditions does not increase the risk of female breast or gynecologic cancers: A population-based propensity score-matched cohort study

Serum levels of prostate specific antigen, free PSA, [-2]proPSA, fPSA/tPSA ratio, Prostate Health Index, and glycosylation patterns of free PSA in patients with benign prostatic hyperplasia pharmacotherapy.

The medication used to treat benign prostate hyperplasia (BPH), a common condition in men over 50 years of age, can alter the levels of biomarkers used in prostate cancer detection. Commonly used medications for BPH include alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and muscarinic antagonists. We studied the impact of these drugs on total prostate-specific antigen (tPSA), free PSA (fPSA), [-2]proPSA, fPSA/tPSA ratio, and the Prostate Health Index (PHI), as well as novel potential biomarkers in the form of glycan composition of fPSA. Serum samples were collected from 564 males with BPH, with a mean age of 68.5 years. The samples were used to measure levels of tPSA, fPSA, and [-2]proPSA. The fPSA/tPSA and PHI were then calculated. The glycan composition of fPSA was analyzed using lectin-based glycoprofiling. Pharmacotherapy data was collected from the patients' medical records. Alpha-blocker monotherapy was associated with higher fPSA and fPSA/tPSA ratio, and decreased PHI. Levels of tPSA were not impacted. Alpha-blocker and 5-ARI dual therapy was associated with reduced levels of fPSA, [-2]proPSA, and PHI. Therapy combining alpha-blockers and antimuscarinic agents did not significantly influence biomarker levels apart from an increase in a Maackia amurensis lectin-recognized glycan originating in fPSA. BPH pharmacotherapy notably affects prostate cancer biomarkers. Recognizing the impact of pharmacotherapy is crucial for achieving an accurate diagnosis of prostate cancer and for planning treatment.

Inhibition of 5-alpha reductase attenuates cardiac oxidative damage in obese and aging male rats via the enhancement of antioxidants and the p53 protein suppression

In aging and metabolic syndrome oxidative stress is a causative factor in the cardiovascular pathology. Upregulation of 5-⍺ reductase is associated with cardiac hypertrophy but how inhibition of 5-⍺ reductase affects cardiometabolic function during oxidative damage under those conditions is unclear. Our hypothesis was that Finasteride (Fin), a 5-⍺ reductase inhibitor, promotes an antioxidant response, leading to an improvement in cardiac function in obese and aging rats. Male rats were divided into 3 groups including normal diet (ND) fed rats, ND-fed rats treated with d-galactose (D-gal) to induce aging, and high-fat diet (HFD) fed rats to induce obesity. Rats received their assigned diet or D-gal for 18 weeks. At week 13, rats in each group were divided into 2 subgroups and received either a vehicle or Fin (5 mg/kg/day, oral gavage). Cardiometabolic and molecular parameters were subsequently investigated. Both D-gal and HFD successfully induced cardiometabolic dysfunction, oxidative stress, mitochondrial dysfunction, and DNA fragmentation. Fin treatment did not affect metabolic disturbances; however, it reduced cardiac sympathovagal imbalance, cardiac dysfunction through the inhibition of oxidative stress and promoted antioxidants, resulting in reduced p53 protein levels and DNA fragmentation. Surprisingly, Fin induced insulin resistance in ND-fed rats. Fin effectively improved cardiac function in both models by enhancing antioxidant levels, suppressing oxidative stress and DNA fragmentation. However, Fin treatment did not confer any beneficial effects on metabolic status. Fin administration effectively improved cardiac sympathovagal balance and cardiac function in rats with oxidative damage induced by either D-gal or HFD.

Trends in drug treatment of benign prostatic hyperplasia in Japan based on the National Database Open Data.

This study examined prescription trends for benign prostatic hyperplasia (BPH) drug therapy in Japan over the past decade, focusing on drugs rated as grade A according to Japanese clinical guidelines. Using the National Database Open Data, this study analyzed prescription data from the fiscal years of 2014 to 2021, tracking α1-blockers, 5α-reductase inhibitors, and phosphodiesterase type 5 inhibitors. We adjusted for demographics and calculated medication costs to determine prescribing patterns and changes in drug utilization. Prescriptions for α1-blockers increased from 9898 per 1000 males in 2014 to 12 613 in 2021. Prescriptions for 5α-reductase inhibitors rose from 1441 per 1000 males in 2014 to 2310 in 2021. Tadalafil prescriptions saw a significant increase, from 900 in 2015 to 2520 in 2021. Despite these increases, the overall market size for BPH drugs decreased from 664 million dollars in 2014 to 279 million dollars in 2021, indicating a shift toward generic medications driven by healthcare policies. Although BPH medication prescriptions are increasing, driven by Japan's aging population and clinical guidelines, market dynamics are shifting owing to generic and government price adjustments. This analysis underscores the changing BPH treatment landscape in Japan, highlighting the importance of continuous evaluation of treatment efficacy and cost-effectiveness in evolving healthcare policies and demographics.

A Review of the Azasteroid-type 5-alpha Reductase Inhibitors for the Management of Benign Prostatic Hyperplasia

Background: Prostate cancer is one of the most complex cancer and most common in elderly males. The prostate gland's malignant growth known as benign prostatic hyperplasia (BPH) is associated with lower urinary tract symptoms (LUTS) such as frequency hesitancy, and urgency. Various treatment strategies have been employed for management of prostate cancer. Due to its prolonged treatment, varying clinical treatment and high association with treatment related morbidity raise serious questions about the ideal treatment strategy for the patients. Except for skin cancer, prostate cancer is the most frequent cancer among men. Introduction: Prostate cancer cases were estimated at 14, 14,259 and 3, 75,304 persons were died globally in 2020. It is the fourth most frequent type of cancer to be discovered worldwide. It impacts over 75% of people by the time they turn 65 and its prevalence increases with age. It seems sensible that 5-alpha reductase inhibitors prevent the conversion of testosterone to dihydrotestosterone and would be used to treat benign prostatic hyperplasia because high levels of the 5-alpha reductase enzymes in humans lead to excessive levels of dihydrotestosterone in peripheral tissues. Methods: Finasteride (Proscar) and dutasteride (Avodart) are 5-alpha reductase inhibitors (5-ARIs) used in the treatment of lower urinary tract symptoms (LUTS) with prostatic enlargement as these suppress the androgens. Finasteride in clinical trials shows a 25% reduction in prostate cancer in randomized trials. Dutasteride (Avodart) shows the reduction in risk of prostate cancer by 23 % (approx.) but it also affects the detection of prostate cancer by affecting the levels of prostate-specific antigen. Results: The structural requirements for potential 5-alpha reductase inhibitors might be revealed via ligand-based comparative pharmacophore research employing the known strong inhibitors. These approaches can generate data can be utilized to create more effective and selective inhibitors that pharmaceutical industries can produce at a lesser price. Conclusion: 5-alpha reductase inhibitors are useful in the management of prostate cancer. However, further studies are needed to elucidate the optimal utilization, long-term effects and potential risks in prostate cancer treatment. All 5-alpha reductase inhibitor subcategories have been addressed in this review.

The association of 5-alpha reductase inhibitors treatment with prostate cancer in benign prostate hyperplasia patients: A population-based case-control study

Purpose: Benign prostatic hyperplasia (BPH) is the most common cause of difficult voiding in elderly men. Alpha-blockers and 5-alpha reductase inhibitors (5ARIs) are evidence-based standards of care in treating BPH according to current guidelines. We have conducted a nationwide population-based study to evaluate the association of 5ARIs treatment with prostate cancer in patients with benign prostate hyperplasia. Materials and methods: Between 2005 and 2010, patient data from the National Health Insurance Research Database were obtained. Newly diagnosed patients with BPH were divided into 2 groups: prostate cancer group and BPH group. We conducted a retrospective study on their history of medication usage with 5ARIs. Results were compared with a matched noncancerous control group. The outcome measurements were the incidence and the prostate cancer diagnosis-free survival rate after the BPH index date. Statistical analyses included t test, chi-square test, multivariable logistic regression analysis, and Kaplan-Meier curves with log-rank tests. Results: A total of 18,620 newly diagnosed patients with BPH were selected. After eliminating patients according to the exclusion criteria, a total of 17,716 patients were enrolled as the study subjects. Among them, 530 patients (2.99%) developed prostate cancer and 17,186 (97.01%) did not. The mean age of the total case-control study was 69.1 years. The odds ratio of prostate cancer in patients with BPH with 5ARIs usage was 1.14 with a P value of 0.539, indicating that the use of 5ARIs was not associated with a higher risk of developing prostate cancer. Multivariate analysis showed no significant intergroup difference in the risk of developing prostate cancer (odds ratio = 1.14, 95% CI: 0.75–1.74, P = 0.539). A subgroup survival analysis, observing the time interval from BPH diagnosis to the development of prostate cancer based on 5ARIs usage, revealed a nonsignificant difference in the prostate cancer diagnosis-free survival rate, with a P value of 0.3592. Conclusion: The 5ARI usage in patients with BPH was not associated with increased risk of developing prostate cancer. Furthermore, the prostate cancer diagnosis-free survival rate, when stratified based on 5ARIs usage, showed no statistically significant difference. Under our health insurance regulation and clinical practice, 5ARIs are consider safe in treating BPH.

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data

BackgroundIncreasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. MethodsThe MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. ResultsOverall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58–1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87–1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. ConclusionsThe use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

Analysis of breast health outcomes in women on oral 5-alpha reductase inhibitors: A single-center retrospective cohort study

Analysis of breast health outcomes in women on oral 5-alpha reductase inhibitors: A single-center retrospective cohort study

Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos

Steroid 5α-reductase (SRD5A) is a crucial enzyme involved in steroid metabolism, primarily converting testosterone to dihydrotestosterone (DHT). Dutasteride, an inhibitor of SRD5A types 1 and 2, is widely used for treating benign prostatic hyperplasia. An adverse outcome pathway (AOP) has been documented wherein SRD5A inhibition decreases DHT synthesis, leading to reduced levels of 17β-estradiol (E2) and vitellogenin (VTG), subsequently impairing fecundity in fish (AOP 289). However, the molecular and cellular mechanisms underlying these effects remain poorly understood. In this study, we assessed the impact of SRD5A inhibition on zebrafish embryos (Danio rerio). Exposure to dutasteride resulted in decreased DHT, E2, and VTG levels, showing a positive correlation. Dutasteride also downregulated the expression of reproduction-related genes (srd5a2, cyp19a1, esr1, esr2a, esr2b, and vtg), with interrelated reductions observed across these levels. Docking studies suggested that dutasteride's effects may operate independently of androgen receptor (AR) and estrogen receptor (ER) interactions. Furthermore, co-exposure of dutasteride (0.5 or 2 μM) with 0.5 μM DHT revealed gene expression levels comparable to the control group. These findings underscore DHT's pivotal role in modulating estrogenic function and the interplay between estrogenic and androgenic responses in vertebrates. Our proposed AOP model offers insights into mechanistic gaps, thereby enhancing current understanding and bridging knowledge disparities.

Characterizing prostate zonal shape changes associated with 5α-reductase inhibitors using MRI.

Benign prostatic hyperplasia (BPH) is a prevalent medical disorder that primarily affects elderly males. It is distinguished by enhanced angiogenesis of the prostate, aggravating lower urinary tract symptoms (LUTS) and diminishing overall quality of life. Dutasteride, a 5α-reductase inhibitor, has emerged as a significant therapeutic choice for BPH owing to its efficacy in reducing prostate volume. The objective of this study is to analyze alterations in the shapes of prostate zones resulting from dutasteride treatment of BPH, using MRI. We examined 19 drug-administered patients and 33 non-drug-administered patients. MRI sections of all participants before and after drug treatment were collected retrospectively. The transition zone and peripheral zone of the prostate were marked with selected landmarks using TPSDIG v2.04. Generalized Procrustes Analysis was used to analyze shapes statistically. Our results showed that the 5α-reductase inhibitor significantly altered the shape of the transition zone by narrowing its posterior part. There were significant statistical differences between the drug-administered and non-drug-administered groups in the initial and final shapes of the transition zone. These findings indicate that the use of 5α-reductase inhibitors yielded favorable outcomes in terms of prostate size reduction and amelioration of symptoms associated with BPH.

Change in prostate tissue gene expression following finasteride or doxazosin administration in the medical therapy for prostatic symptoms (MTOPS) study

Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Unsupervised clustering revealed molecular subgroups characterized by expression changes in a large set of genes associated with resistance to finasteride, a 5α-reductase inhibitor. Pathway analyses within this gene cluster found finasteride administration induced changes in fatty acid metabolism, amino acid metabolism, immune response, steroid hormone metabolism, and kinase activity within the transitional zone. We found that patients without this transcriptional response were highly likely to develop clinical progression, which is expected in 13.2% of finasteride-treated patients. Importantly, a patient’s transcriptional response to finasteride was associated with their pre-treatment kinase expression. Further, we identified novel expression signatures of finasteride resistance among the transcriptionally responded patients. These patients showed different gene expression profiles at baseline and increased prostate transitional zone volume compared to the patients who responded to the treatment. Our work suggests molecular mechanisms of clinical resistance to finasteride treatment that could be potentially helpful for personalized BPH treatment as well as new drug development to increase patient drug response.

Unveiling the potential of novel 5α-reductase inhibitors via ligand based drug design, molecular docking and ADME predictions to manage BPH

Benign prostatic hyperplasia (BPH), a prevalent condition among elderly males characterized by the non-cancerous enlargement of the prostate gland is due to the increased stromal and epithelial cell numbers. The enlargement is driven by an active dihydrotestosterone (DHT), synthesized from its prohormone testosterone under the catalytic effect of 5α-reductase Type-II (5-AR2) enzyme. To reduce the increased DHT levels and ultimately to control prostate growth, inhibition of the 5-AR represent an interesting therapeutic target. The 3D crystallography structure 5-AR2, a member of the steroid 5-AR family belonging to the class of oxidoreductase has been resolved recently and opened the door to develop selective novel inhibitors of 5-AR Type-II isoform using molecular modeling techniques. The Force field and Gaussian-field three-dimensional quantitative structure–activity relationship (3D-QSAR) models have been developed using 42 selective 5-AR2 inhibitors belonging to chemical class of steroidal androstene. Partial least squares analysis produced statistically significant model with R2training = 0.9367, 0.9459 and predictability Q2test = 0.7233, 0.8595. Developed 3D-QSAR model include steric, electrostatic, hydrophobic, and hydrogen bond acceptor and donor field indicators, whereas the potential field contributions indicated the importance of steric feature in governing their biological activity. Protein-ligand interaction pattern analysis revealed that amino acid residues GLU57, ARG114, TYR91 present in the active site of 5-AR2 are crucial for lower energy complexes with good binding affinity. Identified hits were finally adjudged for their druggability by determining in-silico pharmacokinetic parameters. Further, RMSD, binding free energy calculations and post MD analysis demonstrated the enhanced binding affinity with better ΔGbind value (-79.6 ± 3.9 kcal/mol) of identified ligand A-10 than the reference molecule finasteride (-69.13 ± 4.69 kcal/mol). Combined approach of ligand-based and structure-based models have provided an improved understanding of the structural properties of androstene class that may be further used to develop novel 5-AR2 inhibitors to be useful in BPH.

Intraoperative Iris Behavior during Phacoemulsification Maneuvers in Rabbits Treated with Selective α1-Blocker, 5α-Reductase Inhibitor, or Anxiolytic Medication.

This prospective, experimental study aims to evaluate the association between administration of α-blocker, 5α-reductase inhibitor, or anxiolytic medications and intraoperative floppy iris syndrome (IFIS) using a rabbit animal model. A total of 31 Metis rabbits were distributed into four groups as follows: 10 rabbits given tamsulosin, 10 rabbits given finasteride, 5 rabbits who received lorazepam, and 6 treatment-naive animals in the control group. Dosing was calculated according to body surface area ratio of man to rabbit, with a dosing duration of 43 days for all groups. Phacoemulsification maneuvers were performed by a single surgeon, who was blinded to group allocation. Any intraoperative billowing of the iris was noted and subsequently graded from 0 to 3. Higher incidences of iris billowing were found in the tamsulosin-dosed animals [OR = 8.33 (CI 95% 0.63-110.09)], (p = 0.13), the finasteride group [OR = 11.6 (CI 95% 0.92-147.6)], (p = 0.11), and the lorazepam group [OR = 7.5 (CI 95% 0.45-122.8)], (p = 0.24), as opposed to the control. Administration of α-blocker tamsulosin, 5α-reductase inhibitor finasteride, or anxiolytic medication lorazepam induces altered intraoperative iris behavior. These results correspond with previous studies and further solidify the hypothesis that systemic medication, administered both long and short-term, influences surgical parameters in cataract surgery. The present study can become the basis for further clinical or experimental research.

Current Understanding of Androgen Signaling in Prostatitis and its Treatment: A Review.

Chronic prostatitis is a highly prevalent condition that significantly impacts the quality of life and fertility of men. Because of its heterogeneous nature, there is no definitive treatment, which requires ongoing research into its etiology. Additionally, the association between prostatitis and an elevated risk of prostate cancer highlights the importance of comprehending androgen involvement in prostatitis. This paper examines the current understanding of androgen signaling in prostatitis and explores contemporary therapeutic approaches. It was reviewed Medline articles comprehensively, using keywords such as nonbacterial prostatitis, prostatitis infertility, androgen role in prostatitis, and chronic pelvic pain. Several cellular targets are linked to androgen signaling. Notably, the major tyrosine phosphatase activity (cPAcP) in normal human prostate is influenced by androgen signaling, and its serum levels inversely correlate with prostate cancer progression. Androgens also regulate membrane-associated zinc and pyruvate transporters transduction in prostate cells, suggesting promising avenues for novel drug development aimed at inhibiting these molecules to reduce cancer tumor growth. Various therapies for prostatitis have been evaluated, including antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha-blockers, 5α-reductase inhibitors, and androgen receptor antagonists. These therapies have demonstrated varying degrees of success in ameliorating symptoms.In conclusion, aging decreases circulating T and intraprostatic DHT, altering the proper functioning of the prostate, reducing the ability of androgens to maintain normal Zn2+ levels, and diminishing the secretion of citrate, PAcP, and other proteins into the prostatic fluid. The Zn2+-transporter decreases or is absent in prostate cancer, so the pyruvate transporter activates. Consequently, the cell ATP increases, inducing tumor growth.

Association of Terazosin, Doxazosin, or Alfuzosin Use and Risk of Dementia With Lewy Bodies in Men.

Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)-producing enzyme in glycolysis. It is hypothesized that the increase in energy availability in the brain may slow or prevent neurodegeneration, potentially by reducing the accumulation of alpha-synuclein. Recent work has suggested a potentially neuroprotective effect of the use of Tz/Dz/Az in Parkinson disease in both animal and human studies. We investigated the neuroprotective effects of Tz/Dz/Az in a closely related disease, dementia with Lewy bodies (DLB). We used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or 2 comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed up the matched cohorts forward to estimate the hazard of developing DLB using Cox proportional hazards regression. Men who were newly started on Tz/Dz/Az had a lower hazard of developing DLB than matched men taking tamsulosin (n = 242,716, 728,256 person-years, hazard ratio [HR] 0.60, 95% CI 0.50-0.71) or 5ARI (n = 130,872, 399,316 person-years, HR 0.73, 95% CI 0.57-0.93). while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (n = 159,596, 482,280 person-years, HR 1.17, 95% CI 0.96-1.42). These results were robust to several sensitivity analyses. We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality. This study provides Class III evidence that Tz/Dz/Az use reduces the rate of developing DLB in adult men.

The impact of preoperative 5-alpha reductase inhibitors on functional outcomes and health-related quality of life following radical prostatectomy – A propensity score matched longitudinal study

ObjectivesWhile the impact of treatment with 5-alpha Reductase Inhibitors (5-ARI) on the risk of cancer-related mortality in men with prostate cancer (PC) has been extensively studied, little is known about the impact of preoperative 5-ARI use on patient-reported outcomes (PROs) following radical prostatectomy (RP).MethodsWithin our prospectively maintained institutional database of 5899 patients treated with RP for PC (2008– 2021), 99 patients with preoperative 5-ARI therapy were identified. A 1:4 propensity-score matched analysis of 442 men (n = 90 5-ARI, n = 352 no 5-ARI) was conducted. Primary endpoint was continence recovery using daily pad usage and ICIQ-SF. Health-related quality of life (HRQOL) was assessed using the validated EORTC QLQ-C30 and PR25 questionnaires. Multivariable Cox-regression-models tested the effect of preoperative 5-ARI treatment on continence-recovery (p < 0.05).ResultsPatients were followed up perioperatively, followed by annual assessments up to 60mo postoperatively. Preoperative mean ICIQ-SF score (2.2 vs. 0.9) was significantly higher in the 5-ARI cohort (p = 0.006). 24mo postoperatively, 68.6% (no 5-ARI) vs. 55.7% (5-ARI) had full continence recovery (p = 0.002). Multivariable Cox regression analysis, revealed preoperative 5-ARI treatment as an independent predictor for impaired continence recovery (HR 0.50, 95% CI 0.27–0.94, p = 0.03) In line, general HRQOL was significantly higher for patients without 5-ARI only up to 24mo postoperatively (70.6 vs. 61.2, p = 0.045). There was no significant impact of preoperative 5-ARI treatment on erectile function, biochemical recurrence-free survival and metastasis-free survival.ConclusionsPre-RP 5-ARI treatment was associated with impaired continence outcomes starting 24mo postoperatively, suggesting that preoperative 5-ARI treatment can impair the long-term urinary function recovery following RP.