5α-reductase Inhibitors Research Articles

GC-MS and HPLC Supported Phytochemical Analysis of Tridax

Background: Tridax procumbens (T. procumbens) Linn. is a daisy family commonly known as “Ghamra” or “Coat Buttons”, the native of this plant is tropical America, Asia, Australia and throughout India, it is also distributed in roadside, waste grounds, riverbanks mainly during rainy season. It has medicinal properties due to presence of some bioactive chemical constituents. Objectives: Phytochemical analysis of Tridax procumbens (T. procumbens) Linn leaves were carried out in different extraction. Methods: Qualitative, Quantitative, HPLC, GC- MS & UV-FTIR. Results: The phytochemical qualitative analysis of Tridax procumbens (T. procumbens) Linn was performed with various extraction. The hydro-ethanolic extract contains a high concentration of phytochemical constituents than ethanol, hexane, petroleum ether & aqueous extracts. The phytochemical constituents found were tannin, saponin, flavonoids, steroids, terpenoids, triterpenoids, alkaloids, anthraquinone, polyphenol, glycoside, coumarins and emodin. The wide range of bioactive compounds were found to have antitoxicity, anticancer, antimicrobial, antifungal, antioxidant, antitumor, antimicrobial, antifouling, nematicide, antiarthritic, hepatoprotective, hypocholesterolemic, 5-alpha reductase inhibitor, antihistaminic, anticoronary insectifuge, antieczemic, antiacne, anti-androgenic flavour, pesticide, lubricant, haemolytic 5-alphareductase inhibitor, antipsychotic, potent antibacterial agent, antimalarial activites. Conclusion: Hydro-ethanolic extract showed several phytochemical constituents and bioactive compounds which can be used for therapeutic purposes.

Incidental Prostate Cancer Diagnosis Is Common After Holmium Laser Enucleation of the Prostate

ObjectiveTo determine the incidence of incidental prostate cancer detection (iPCa) after holmium laser enucleation of the prostate (HoLEP). The published rate of iPCa after HoLEP is widely variable from 7-23% and we aim to define preoperative risk factors for iPCa to inform risk adjusted preoperative evaluation for prostate cancer. MethodsConsecutive patients undergoing HoLEP from 2018-2022 were included and comprehensive clinical data abstracted from a prospectively maintained database. iPCa was defined as a diagnosis of PCa on pathologic examination of the HoLEP specimen. Patients with and without iPCa were compared with respect to pre-operative clinical variables. ResultsOf 913 HoLEP patients, 183 (20%) were diagnosed with iPCa. Most patients (95%) had a pre-operative PSA, 9% had negative MRI, and 30% had negative prostate biopsy. On multivariable analysis, PSA density (OR 1.06; 95% CI 1.03, 1.10; p<0.001), preoperative biopsy status (OR 0.47, CI 0.30, 0.75; p=0.002), and current 5-alpha reductase inhibitor (5-ARI) use (OR 0.64, CI 0.43, 0.97; p=0.034), were associated with iPCa diagnosis. ConclusionsIn a significantly pre-screened population, we identified a 20% rate of iPCa after HoLEP. Preoperative characteristics associated with iPCa diagnosis included increasing age, increasing PSA density, and current 5-ARI use. However, these factors alone may be of limited clinical utility to prospectively identify patients at high risk of iPCa diagnosis. We suggest and advocate for development of a standardized, risk adapted evaluation focused on expanded use of imaging and selective biopsy to prioritize identification of clinically significant prostate cancers prior to non-oncologic surgery.

Scientific Evaluation of A Unani Pharmacopoeia-Based Formulation on BPH in Animal Model

BPH (Benign prostatic hyperplasia) is a common problem of the prostate gland that affects elderly men with age and major cause of lower urinary tract symptoms (LUTS) like urgency of urination, frequency of micturition, dysuria, nocturia, dribbling, and burning of urine. If left untreated, the condition can lead to severe urinary retention, recurrent UTI, and, in severe cases, renal failure, etc. Alpha-blockers and 5-alpha reductase inhibitors (5-ARIs) are two main classes of drugs that are used in conventional therapy to treat BPH. These phytochemical therapies are extremely effective, but standard control methods have unfavorable side effects too. Conversely, evidence, though limited, has shown that alternative medicines are safer and have the potential to improve LUTS and quality of life, in addition to improving sexual dysfunction in patients with BPH. The purpose of the study is to assess the efficacy of 50% hydroalcoholic UPBF extract on BPH in TP-induced rats, and the effects of the drug were compared between the treated and untreated groups. The experimental design for anti-BPH activity was carried out following the Bhavin model. 48 Wistar rats were divided into 6 groups, with 8 rats in each group. Group 1, plane control (untreated rats), group 2, negative control (treated with TP 5 mg/kg), group 3, negative control (treated with TP+ finasteride 1 mg/kg), and groups 4,5 and 6 served as tests controls (A, B, and C) treated with TP+ UPBF extract 100 mg/kg, 150 mg/kg, and 200 mg/kg as low, medium, and high doses, respectively. BPH was induced in rats by administration of testosterone propionate (TP) in arachis oil, and treatment was done orally with a standard drug (finasteride) and a test drug (UPBF) once a day for 28 consecutive days. Before and after initiating the study, each rat was weighed and documented, and after 28 days, the collection of blood samples and the prostate gland was done under light anesthesia. The parameters of the study were accessed, like prostate weight, prostate-to-body weight ratio, histopathological investigation of the prostate, percentage of inhibition, percentage of recovery, and determination of ST and STP levels. Data from the results were expressed as the mean ± standard error of the mean (SEM). Evaluation between group results was carried out with the one-way ANOVA test followed by Tukey’s test, and the significant value of p was &lt;0.05. Both histopathological and biochemical parameter results showed significant improvements in rats treated with finasteride and UPBF extract at a dose of 200 mg/kg (p&lt;0.001). In addition, ST and STP levels showed a significant reduction in comparison with the BPH group. It can be concluded from the findings of the results in both biochemicals and histopathological parameters that the test drug (UPBF) possesses significant effects against the TP-induced BPH in rats. The findings suggested that the test drug can be used independently in the management of BPH as well as for lower urinary tract symptoms.

Exploring the Enigma of 5-ARIs Resistance in Benign Prostatic Hyperplasia: Paving the Path for Personalized Medicine.

Despite the widespread utilization of 5-alpha reductase inhibitors (5-ARIs) for managing benign prostatic hyperplasia (BPH), certain BPH patients exhibit unresponsiveness to 5-ARIs therapy. This paper provides a comprehensive overview of the current perspectives on the mechanisms of 5-ARIs resistance in BPH patients and integrates potential biomarkers and underlying therapeutic options for 5-ARIs resistance. These findings may facilitate the development of novel or optimize more effective treatment options, and promote personalized medicine for BPH. The pathways contributing to resistance against 5-ARIs in certain BPH patients encompass epigenetic modifications, shifts in hormone levels, autophagic processes, and variations in androgen receptor structures, and these pathways may ultimately be attributed to inflammation. Promisingly, novel biomarkers, including intravesical prostatic protrusion, inflammatory factors, and single nucleotide polymorphisms, may offer predictive insights into the responsiveness to 5-ARIs therapy, empowering physicians to fine-tune treatment strategies. Additionally, on the horizon, GV1001 and mTOR inhibitors have emerged as potential alternative therapeutic modalities for addressing BPH in the future. After extensive investigation into BPH's pathological processes and molecular landscape, it is now recognized that diverse pathophysiological mechanisms may contribute to different BPH subtypes among individuals. This insight necessitates the adoption of personalized treatment strategies, moving beyond the prevailing one-size-fits-all paradigm centered around 5-ARIs. The imperative for early identification of individuals prone to treatment resistance will drive physicians to proactively stratify risk and adapt treatment tactics in future practice. This personalized medicine approach marks a progression from the current standard treatment model, emerging as the future trajectory in BPH management.

Finasteride effectively attenuates the impairments of left ventricular function and cardiac sympathovagal balance in both aging and obese male rats via reducing systemic oxidative stress

Abstract Background Cardiovascular diseases are commonly found in the elderly and obese population manifested by left ventricular (LV) dysfunction and impaired cardiac sympathovagal balance. Finasteride (FIN), a 5-alpha reductase inhibitor (5-ARI), is a universal prescription for patients with benign prostatic hyperplasia (BPH). Since BPH is commonly found in obesity and aging, it is essential to investigate whether FIN could have an impact on the LV function and cardiac sympathovagal balance in either elderly or obese conditions. Purpose We tested the hypothesis that impaired LV function and cardiac sympathovagal balance are observed in aging and obese conditions, and FIN improves these parameters through a reduction of systemic oxidative stress in both aging and obese male rats. Methods Twenty-four male Wistar rats (aged 8 weeks old) were randomly divided into 3 groups (n=8/group) to receive one of the followings: 1) normal diet (ND) feeding, 2) ND feeding with D-galactose injection (150 mg/kg/day, subcutaneous injection, 18 weeks) for creating an aging model, and 3) HFD feeding for 18 weeks for creating an obesity model. At week 13, rats in each group were divided into 2 subgroups (n=4/subgroup) and received either a vehicle (drinking water) or FIN (5 mg/kg/day) via oral gavage. At the end of treatment, echocardiography was performed to assess LV function, and the heart rate variability (HRV) was determined to quantify cardiac sympathovagal balance. The blood was collected, and serum was used to determine serum malondialdehyde (MDA) levels as a marker of systemic oxidative stress. Results At week 13, D-galactose injection successfully induced aging as indicated by increasing cardiac p53 protein expression. HFD also caused obesity in those rats as indicated by increased body weight and visceral fat weight. LV dysfunction (as indicated by reduced %LVEF and %LVFS) and cardiac sympathovalgal imbalance (as indicated by an increased LF/HF ratio) were observed in both models (Figure 1A-C). This functional impairment was associated with an increased MDA levels (Figure 1D). Treatment with FIN successfully reduced cardiac sympathovagal imbalance in both models (Figure 1C); however, an improvement of LV function was found only in aging rats-treated with FIN (Figure 1A, B). Consistent with a reduction of cardiac sympathovagal imbalance, FIN decreased systemic oxidative stress in both models (Figure 1D). Conclusions FIN effectively improved cardiac sympathovagal balance in rats under both aging and obese conditions. However, FIN reduced LV dysfunction only in aging rats. Interestingly, FIN did not affect these cardiac parameters in normal healthy rats. These findings suggest the cardioprotective potential of FIN in both aging and obese populations.

Clinical Effects of Oral Supplementation of Gamma-Cyclodextrin Curcumin Complex in Male Patients with Moderate-To-Severe Benign Prostatic Hyperplasia-Related Lower Urinary Tract Symptoms

Introduction: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTSs) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN^® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN^®) as single or combination therapy for BPH. Methods: Men with moderate-severe LUTS/BPH, receiving a 6-month supplementation with QURMIN^® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign Prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. Results: The 1:1 propensity score matching resulted in a treatment-naïve (n = 152), an alpha-blocker only (AB) (n = 138) and AB + 5-alpha reductase inhibitors (5-ARIs) (n = 78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (−3.9, p < 0.001), IPSS-voiding (−2.0, p = 0.011), IPSS-total (−5.9, p < 0.001), IPSS-QoL (−3.9, p < 0.001), BII (−2.0, p < 0.001), Q_max (+3.1 mL/s, p < 0.001), Q_mean (+1.9 mL/s, p = 0.005), post-void residual volume (−7.7 mL, p < 0.001), and PSA (−0.3 ng/mL, p = 0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage (−2.7, p < 0.001), IPSS-voiding (−1.3, p = 0.033), IPSS-total (−3.5, p < 0.001), IPSS-QoL (−1.1, p = 0.004), BII (−1.7, p = 0.006), Q_max (+1.0 mL/s, p = 0.006), and PSA (−0.2 ng/mL, p = 0.01). Patients taking curcumin and AB + 5-ARI showed improvement in IPSS-storage (−1.3, p = 0.007), IPSS-total (−1.6, p = 0.034), IPSS-QoL (−1.1, p < 0.001), and BII (−2.0, p < 0.001). No adverse reactions were reported for curcumin supplementation. Conclusion: QURMIN^® (CAVACURMIN^®) led to significant improvements in symptom burden, uroflow parameters, and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.

THU372 Finasteride Induced Hyperglycemia

Abstract Disclosure: V. Bose: None. D.S. Martinez: None. Objective: Finasteride is a 5-alpha reductase inhibitor that is often prescribed to treat benign prostatic hyperplasia in men. It prevents the conversion of testosterone to dihydrotestosterone. Dihydrotestosterone has numerous physiological actions including having effects on physiological function of liver and pancreatic β-cells. While the medicine does not have hyperglycemia as an adverse effect on its profile, this is a case presentation of worsening hyperglycemia in a diabetic patient who was started on 5-alpha reductase inhibitor. Methods: The patient’s clinical course with laboratory data is presented. Results: The patient is a 69 year old obese male presented for hyperglycemia management. He had been treated with GLP1 agonist, SGLT2i and NPH. He noted that since starting finasteride in 2018, his fingerstick glucose levels were higher compared to prior readings. His hemoglobin A1c was also noted to have increased from 7% to 8.2%. He also reported some weight gain. Conclusion: In this case, one can see that the use of 5-alpha reductase inhibitor precipitated worsening hyperglycemia. The inhibition of androgens to their various metabolites may result in pathophysiological states that present as hyperglycemia via insulin resistance and liver disturbances. In patients with diabetes, the addition of finasteride or dutasteride should be cautiously monitored and if possible, avoided to limit worsening hyperglycemia and diabetic complications. Reference: Traish AM. Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm. World J Mens Health. 2020 Jul;38(3):323-337. doi: 10.5534/wjmh.200012. Epub 2020 Mar 20. PMID: 32202088; PMCID: PMC7308241. Presentation: Thursday, June 15, 2023

A Comparison of Safety and Efficacy between Silodosin Monotherapy Versus Silodosin with Tadalafil Add on Therapy in Patients with Benign Prostatic Hyperplasia

Background: For relieving symptoms of LUTS due to BPH treatment modalities are watchful waiting, medical treatment and surgery. Among medical treatment, options are alpha 1 adrenoreceptor blockers, 5 alpha reductase inhibitors and recently introduced phospodiesterase 5 inhibitors or combination therapy. Objective: To compare the safety and efficacy of silodosin versus silodosin and tadalafil for treating patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Materials and Methods: This prospective observational study was conducted in the Department of Urology, BSMMU, Dhaka from April 2020 to March 2021. A total of 66 patients with LUTS due to BPH were selected by purposive sampling on the basis of selection criteria from OPD of Urology, BSMMU. They were randomly divided into two groups: according to odd or even hospital number and label as A group (odd no) and B group (even no). Group-A were provided with silodosin 8.0 mg daily and group-B were provided with silodosin 8.0 mg and tadalafil 5.0 mg daily (B group). Two patients from each group were excluded due to adverse effect and one patients from each group was lost to follow-up. Final analysis was done on sixty patients (30 from each group). The patients were assessed by IPSS, Qmax and PVR. The results were expressed as frequency &amp; percentage (categorical data) and mean ± SD (numerical data). Unpaired t-tests and paired t tests were performed as applicable using SPSS 22.0 and p &lt;0.05 was considered as the level of significance. Results: Out of sixty six patients, sixty patients completed the study. Two patients from group A was suffering from hypotension and headache and two patients from group B was suffering from ejaculatory dysfunction and dizziness, one patient from each group was lost after 1st follow up, so they were excluded from study. Maximum study subjects were within 51 to 70 years of age in both groups. Mean age of the study subjects was 57.13 ± 9.36 years in Group-A and 59.33 ± 7.09 years in Group-B. Mean prostate volume of the study subjects was 37.93 ± 13.19 ml in Group-A and 35.50 ± 10.57 ml in Group-B. IPSS was reduced to 21.90±3.68 after 6 weeks and 18.90 ± 3.79 after 12 weeks from 25.10 ± 3.96 prior to treatment in Group-A. Similarly, in Group- B, IPSS was reduced from 19.67 ± 3.45 after 6 weeks and 16.37 ± 2.03 after 12 weeks from 23.03 ± 4.16 prior to treatment. PVR decreased to 58.00 ± 20.41 after 6 weeks and 42.10 ± 17.40 after 12 weeks from 74.15 ± 26.40 prior to treatment in Group-A. Similarly, PVR in Group-B reduced to 52.70 ± 12.51 after 6 weeks and 33.57 ± 8.97 after 12 weeks from 66.17 ± 15.50 before treatment. After 6 weeks, Qmax increased to 15.67 ± 2.11 and at 12 weeks17.73 ± 2.66 from 13.39 ± 1.83 before treatment in Group-A. Similarly, after 6 weeks, Qmax in Group-B increased to 16.74 ± 1.14 and at 12 weeks18.94±1.31 from 14.17±1.28 before treatment. Conclusion: Improvements in both silodosin (alpha blocker) group and silodosin in combination with tadalafil (PDE 5 inhibitor) group were found to be effective, safe and satisfactory in treating patients with symptomatic BPH. Even though combination group showed better efficacy than silodosin monotherapy group but as per improvement rate it was not statistically significant. Bangladesh J. Urol. 2022; 25(1): 19-27

Conservative and pharmacological treatment of benign prostatic hyperplasia : The German S2e-guideline 2023-part2

Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH, in German guidelines: benign prostatic syndrome [BPS]) is considered the most common disease of the lower urinary tract in men and can have atremendous impact on the quality-of-life of affected patients. Conservative and pharmacological therapy of this disease are of great importance, both in improving LUTS and reducing progression-related complications. Presentation of the conservative and pharmacological treatment options according to the current German S2eguideline on BPS. Summary and overview of chapters9 and10 of the current German S2eguideline on BPS. In addition to acontrolled watchful waiting for BPS patients without an absolute indication for prostate surgery, avariety of phytopharmacological formulations and synthetic drugs according to the symptomatology and clinical progress are available. Phytotherapy should, due to inconsistent study data, only be considered for mild to moderate symptoms. Synthetic drugs include alpha-blockers, 5α-reductase inhibitors, phosphodiesterase inhibitors, antimuscarinics and, more recently, the β3-agonist mirabegron in the current guideline. In addition, various combination therapies are listed and evaluated according to their indications, effects and side effects. The current German S2eguideline on the diagnosis and treatment of BPS provides an evidence-based foundation for finding the best possible and most effective medication.

The post-finasteride syndrome: possible etiological mechanisms and symptoms.

Finasteride and dutasteride, synthetic 5α-reductase inhibitors (5ARIs) are recommended in many guidelines for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms and alopecia despite a variety of side effects like sexual, neurological, psychiatric, endocrinological, metabolic and ophthalmological dysfunctions and the increased incidence of high grade prostate cancer. The sexual side effects are common during the use of the drug but in a small subgroup of patients, they can persist after stopping the drug. This so-called post-finasteride syndrome has serious implications for the quality of life without a clear etiology or therapy. Three types of 5α-reductases are present in many organs in- and outside the brain where they can be blocked by the two 5ARIs. There is increasing evidence that 5ARIs not only inhibit the conversion of testosterone to 5α-dihydrotestosterone (DHT) in the prostate and the scalp but also in many other tissues. The lipophilic 5ARIs can pass the blood-brain barrier and might block many other neurosteroids in the brain with changes in the neurochemistry and impaired neurogenesis. Further research and therapeutic innovations are urgently needed that might cure or relieve these side effects. More awareness is needed for physicians to outweigh these health risks against the benefits of 5ARIs.

Impact of modifiable lifestyle risk factors for prostate cancer prevention: a review of the literature.

Although prostate cancer (PCa) is one of the most common cancers among men, the impact of modifiable risk and protective factors is still being debated. This review aims to qualitatively summarize the most recent studies related to potential healthy lifestyle factors affecting the development of PCa. The literature focusing on modifiable risk factors for prostate cancer was reviewed. Medline and Embase via the Ovid database were searched, and all relevant and inherent articles were analyzed. Non-eligible publications, such as review articles, editorials, comments, guidelines, or case reports, were excluded. This review confirms that there is strong evidence that being overweight or obese increases the risk of advanced prostate cancer (assessed by body mass index (BMI), waist circumference, and waist-hip ratio), particularly considering central adiposity and ethnicity as contributing factors. The possible contribution of smoking still seems not entirely clear, while alcohol seems to affect PCa prevention in patients taking 5α-reductase inhibitors (5-ARIs). Dietary fibers may have anti-inflammatory properties and improve insulin sensitivity by reducing IGF bioactivity. In particular, dietary fiber intake like insoluble and legume fibers may be inversely associated with prostate cancer risk. Also, hyperglycemia and hyperinsulinemia, with untreated diabetic fasting blood glucose levels, could be modifiable prostate cancer risk factors. In two studies, aspirin was associated with a lower risk of lethal PCa and overall mortality. Concerning the role of vitamins, despite conflicting and divergent results, serum retinol concentration seems to be associated with an increased risk of prostate cancer and high-grade prostate cancer. Some studies resulted in disagreement about the role of selenium and vitamin E. We found inconsistent and controversial findings about the association between vitamin D and prostate cancer risk. Far from being conclusive evidence, our findings confirm some strong evidence already found in the previous literature and highlight the need to clarify the role of some risk factors whose role is not yet completely known. This effort would facilitate the cultural and social change that may allow the shift from the treatment of prostate cancer when diagnosed to the real efforts needed for systematic prevention.

Changes of resistance indices after medication in benign prostatic hyperplasia: a prospective study.

This study aimed to determine the relationship between resistive indices (RIs) and changes in prostate size after medical treatment in patients with benign prostatic hyperplasia (BPH). A total of 86 patients with BPH were included in the study, excluding 42 patients with a total prostate volume (TPV) of <30cc or taking α1-adrenergic blockers and 5α-reductase inhibitors (5ARI) before study participation. Therefore, the data for 44 patients were analyzed. All patients were treated with α1-adrenergic blockers and 5ARIs. The variables examined were prostate-specific antigen, International Prostate Symptom Score, quality of lifescore, maximal urinary flow rate, residual urine volume, TPV, transition zone volume, and RIs of the urethral artery and left and right capsular arteries. These variables were assessed at baseline and after 3and 6months of treatment. The mean TPV was 43.5±10.9 and decreased to 35.2±11.5 and 33.9±9.8 after 3and 6months of treatment, respectively (p<0.001). The mean RI of the urethral artery, right capsular artery, and left capsular artery at pretreatment did not decrease significantly. However, comparing the baseline with 3-month data, TPV at 3months/TPV at baseline was significantly correlated with RI changes in the left capsular artery (r=758; P<0.001). In patients with BPH, α1-adrenergic blocker and 5ARI medications for 3and 6months did not result in a significant reduction in the RI of the urethral artery and both capsular arteries. Larger scale, prospective studies are needed to evaluate the relationship between TPV and RI reductions.

Formulation and Evaluation of Herbal Cream for the Management of Androgenetic Alopecia

The current study aimed to develop a herbal hair cream formulation including plant extracts traditionally used for hair growth, and further research was conducted to understand the hair growth capability better using the 5 alpha reductase inhibitory model. 5 alpha reductases, an enzyme confined to the nuclear membrane, converts testosterone into dihydrotestosterone. The 5 alpha-reductase and its metabolite dihydrotestosterone influence various human disorders, including male pattern baldness, benign prostatic hyperplasia (BPH), and prostate cancer. Finasteride and alfatradiol are examples of synthetic medications; however, because of their negative impacts, researchers are currently focused on creating safer 5α-reductase inhibitors from plants. The hair cream formulation contained 0.5% extracts of Hibiscus rosa sinensis flower, Eclipta alba whole plant, and Solanum nigrum plant berries in a ratio of 1:1:1. Plant extracts used in the formulation were characterized by chemical biomarkers. The cream formulation was developed, and the quality control parameters were examined. Furthermore, the produced formulation's 5α-reductase inhibitory activity was tested using finasteride as a positive control. H. rosa sinensis, E. alba, and S. nigrum extracts, which comprise 0.35% oleanolic acid, 4.65% β-sitosterol, and 31.18% linoleic acid, were used in the formulation. HPTLC data revealed that each 10 gm of cream formulation contains 16.68 ± 0.21 mg of linoleic acid, 3.61 ± 0.18 mg of β-sitosterol and 0.380 ± 0.11 mg oleanolic acid. In-vitro results showed a good 5α-reductase inhibitory potential. The IC50 value of the developed formulation was 85.254 ± 0.888 μg/ml, whereas finasteride (positive control) was 223.039 ± 1.367 ng/ml. Thus, the herbal hair cream composition benefits alopecia therapy by inhibiting the 5α- reductase enzyme. In addition, the formulation might be a potential option for further research into its antiandrogenic properties.

624 Medication Cessation Post-TURP: Are We Getting It Right?

Abstract Aim Most patients who have a TURP should be advised to discontinue medication for bladder outflow obstruction secondary to benign prostate hyperplasia (BPH) after their surgery. This closed loop QIP audited whether this was the case, presented the findings to the department and re-audited to see whether there had been a decrease in continuing unnecessary post-TURP medication. Method The QIP began in October 2020 with a retrospective review of 50 patients that underwent a TURP at a large district general hospital. Patient records were reviewed to ascertain if patients were taking alpha-blockers (ABs) or 5 alpha-reductase inhibitors (5ARIs) pre-operatively, and if these were discontinued post-procedure. Any instruction to continue medication post-operatively was noted in the data collection. This data was presented at a departmental research and audit meeting. The second QIP cycle used the same data collection methodology for the subsequent 50 patients who underwent a TURP (June 2021). Results The presentation resulted in a statistically significant decrease in unclear documentation 30% to 10% (p = .0124). Although there was an increase medication discontinuation post-TURP (27.3% to 48%) this wasn’t statistically significant (p = .246). The percentage of patients who were continued on an AB or 5ARI post-op without documentation decreased from 63.3% to 48%, but this change was also not statistically significant (p = .384). Conclusions Simple departmental audits help improve patient safety through clearer documentation and presentation of new literature. It would be beneficial to produce clear guidelines to patients and their primary care physicians to advise to discontinue BPH medication TURP unless otherwise advised by the urologist.

Persistent need for ongoing medical or surgical therapy despite UroLift: Data from an academic center.

The prostatic urethral lift (PUL) is a popular surgical option for benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). Prior 5-year data from the multicenter L.I.F.T. trial suggested durability and a surgical retreatment rate of 13.6% at five years. We assessed the proportion of patients who had ongoing medical or surgical BPH management following PUL. With institutional review board approval, cases of PUL performed from 2015-2020 at our academic institution were retrospectively reviewed for management of BPH following PUL. A total of 209 men were identified, with followup available for 198 (95%). Mean age was 68.9 years and mean followup was 18.5 months. Mean prostate size was 43 g. Patients were discharged from recovery in 97% of cases, with 29% discharged with indwelling or intermittent catheterization. The rate of 30-day complications was 18%, with 89% graded Clavien I-II. Postoperatively, mean improvements in International Prostate Symptom Score (IPSS) and quality of life subscore (QoL) were 5.3 and 1.1 points, respectively. Unplanned emergency room or clinic visits within 30 days of the procedure occurred in 14% and 17% of men, respectively, with 4% requiring hospital readmission. In followup, α-blockers and/or 5α-reductase inhibitors were continued or initiated postoperatively for 44% of men; 20% of men required repeat surgical intervention at a mean of 19.2 months (1.4-56.4), consisting of repeat PUL (30%), transurethral resection of prostate (28%), or thulium laser enucleation (18%). Overall, 53% of men needed medication and/or repeat surgery for BPH following PUL, and this was independent of age, race, prostate volume, intravesical prostate protrusion, baseline IPSS and QOL, stricture, number of implants used, or a history of urinary retention (p>0.05). Most men undergoing PUL require ongoing medical and/or surgical management for BPH. Patients should be counseled as to the likelihood of failure as a unimodal therapy long-term.

Exploring rat corpus cavernosum alterations induced by finasteride treatment and withdrawal.

Despite its efficacy for treating androgenetic alopecia, finasteride, an inhibitor of 5α-reductase (i.e., the enzyme converting testosterone, T, into dihydrotestosterone, DHT), is associated with several side effects including sexual dysfunction (e.g., erectile dysfunction). These side effects may persist after drug suspension, inducing the so-called post-finasteride syndrome (PFS). The effects of subchronic treatment with finasteride (i.e., 20 days) and its withdrawal (i.e., 1 month) in rat corpus cavernosum have been explored here. Data obtained show that the treatment was able to decrease the levels of the enzyme 5α-reductase type II in the rat corpus cavernosum with increased T and decreased DHT levels. This local change in T metabolism was linked to mechanisms associated with erectile dysfunction. Indeed, by targeted metabolomics, we reported a decrease in the nitric oxide synthase (NOS) activity, measured by the citrulline/arginine ratio and confirmed by the decrease in NO2 levels, and a decrease in ornithine transcarbamylase (OTC) activity, measured by citrulline/ornithine ratio. Interestingly, the T levels are negatively correlated with NOS activity, while those of DHT are positively correlated with OTC activity. Finasteride treatment also induced alterations in the levels of other molecules involved in the control of penile erection, such as norepinephrine and its metabolite, epinephrine. Indeed, plasma levels of norepinephrine and epinephrine were significantly increased and decreased, respectively, suggesting an impairment of these mediators. Interestingly, these modifications were restored by suspension of the drug. Altogether, the results reported here indicate that finasteride treatment, but not its withdrawal, affects T metabolism in the rat corpus cavernosum, and this alteration was linked to mechanisms associated with erectile dysfunction. Data here reported could also suggest that the PFS sexual side effects are more related to dysfunction in a sexual central control rather than peripheral compromised condition.

The effect of tranexamic acid on perioperative blood loss in transurethral resection of the prostate: A double-blind, randomized controlled trial.

Bleeding and bleeding-related complications remain common after bipolar transurethral resection of the prostate (TURP) for benign prostatic hyperplasia. This may possibly lead to prolonged postoperative irrigation, catheterization, and hospital stay. The objective of this trial was to evaluate the effect of high-dose tranexamic acid (TXA) on perioperative blood loss in patients treated with bipolar TURP for prostate sizes between 30 and 80 g. We conducted a single-center, prospective, double-blind, randomized controlled trial. Eighty patients were screened for inclusion between March 2020 and January 2023. After exclusion, 65 patients were randomized in two comparable groups. The TXA group (31 patients) received a TXA intravenous loading dose of 10 mg/kg over 30 min before induction, followed by a maintenance dose of 5 mg/kg/h over 12 h. The placebo group (34 patients) received an equal dose of saline infusion. We measured age, weight, preoperative prostate size, anticoagulant use, 5-alpha reductase inhibitor use, preoperative urinary tract infection, American Society of Anesthesiologists score, difference in pre- and 24 h postoperative hemoglobin and hematocrit levels, operative time, resected adenoma weight, duration of postoperative irrigation, total amount of postoperative irrigation fluid, indwelling catheter time, duration of hospital stay, blood transfusion rate, and 4-week complication rate. Baseline characteristics in both groups were comparable. Postoperative hemoglobin decrease in TXA versus placebo group was 1 versus 1.6 mg/dL, respectively (p = 0.04). In addition, the amount of postoperative irrigation fluid (10.7 vs. 18.5 L), irrigation time (24.3 vs. 37.9 h), catheterization time (40.8 vs. 53.7 h), and hospital stay (46.9 vs. 59.2 h) were statistically significant in favor of TXA use. No blood transfusions were carried out. Four-week complication rate was comparable between the two groups. Perioperative high-dose TXA seems beneficial in reducing hemoglobin loss, postoperative irrigation, catheterization time, and hospital stay in bipolar TURP for prostate sizes between 30 and 80 g, without increased risk of TXA-related thromboembolic events.

Evaluating the effects of preoperative treatment with 5-alpha reductase inhibitors in holmium laser enucleation of the prostate

Introduction and aimPatients treated with HoLEP are frequently treated with previous treatments, including 5-alpha-reductase inhibitors (5-ARIs). We investigated the impact of pretreatment with 5-ARIs on perioperative and immediate postoperative parameters in patients treated with HoLEP. Material and methodsA retrospective study was performed using a prospectively collected database including all patients treated with HoLEP at our center between January 2017 and January 2023. The resected tissue weight, enucleation and morcellation efficiency (enucleation weight/time and morcellation weight/ time), postoperative complications, hospital stay and hemoglobin drop have been analyzed. ResultsA total of 327 patients were included. Of these, 173 (52.9%) were treated with 5-ARIs. No differences were found among the perioperative parameters investigated to determine efficiency. No differences were observed in peri- or postoperative complications, hospital stay or hemoglobin drop. ConclusionsTherapy with 5-ARIs had no impact on the immediate postoperative outcomes of patients treated with HoLEP. In our cohort, we observed that the use of 5-ARIs did not affect surgical efficiency, enucleation or morcellation. Further multicenter studies will be necessary to validate these findings.

5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.

Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2yr) and longer-term (> 2yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.

GABA-ergic Modulators: New Therapeutic Approaches to Premenstrual Dysphoric Disorder.

Premenstrual dysphoric disorder (PMDD) is characterized by the predictable onset of mood and physical symptoms secondary to gonadal steroid fluctuation during the luteal phase of the menstrual cycle. Although menstrual-related affective dysfunction is responsible for considerable functional impairment and reduction in quality of life worldwide, currently approved treatments for PMDD are suboptimal in their effectiveness. Research over the past two decades has suggested that the interaction between allopregnanolone, a neurosteroid derivative of progesterone, and the gamma-aminobutyric acid (GABA) system represents an important relationship underlying symptom genesis in reproductive-related mood disorders, including PMDD. The objective of this narrative review is to discuss the plausible link between changes in GABAergic transmission secondary to the fluctuation of allopregnanolone during the luteal phase and mood impairment in susceptible individuals. As part of this discussion, we explore promising findings from early clinical trials of several compounds that stabilize allopregnanolone signaling during the luteal phase, including dutasteride, a 5-alpha reductase inhibitor; isoallopregnanolone, a GABA-A modulating steroid antagonist; and ulipristal acetate, a selective progesterone receptor modulator. We then reflect on the implications of these therapeutic advances, including how they may promote our knowledge of affective regulation more generally. We conclude that these and other studies of PMDD may yield critical insight into the etiopathogenesis of affective disorders, considering that (1) symptoms in PMDD have a predictable onset and offset, allowing for examination of affective state kinetics, and (2) GABAergic interventions in PMDD can be used to better understand the relationship between mood states, network regulation, and the balance between excitatory and inhibitory signaling in the brain.