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Objective: Polycystic ovary syndrome (PCOS) is widely reported among young females, and anti-androgens are used for treating hirsutism and acne in these patients. The protective effects of myo-inositol, oral contraceptives, and insulin sensitizers have been reported on the periodontium and high-sensitivity C-reactive protein (hsCRP) levels in PCOS females. However, cyproterone acetate/ethinyl estradiol (CPA/EE) has not yet been studied. This cross-sectional study explores the periodontal status and systemic inflammation in PCOS women on CPA/EE drug combination compared to females not on medication. Method and materials: A total of 150 participants were enrolled into three groups: 50 newly diagnosed PCOS females not on medication (N-PCOS); 50 PCOS females consuming CPA/EE combination for the last 6 months (PCOS+CPA/EE); and 50 systemically healthy females (control group). Anthropometric, biochemical, periodontal parameters, and health-related quality of life questionnaires were recorded. Results: N-PCOS and PCOS+CPA/EE groups showed a nonsignificant difference in hsCRP levels, Gingival Index, bleeding on probing, waist circumference, and waist-hip ratio (P > .05). Gingival thickness and keratinized tissue width were significantly greater in the PCOS+CPA/EE than the N-PCOS group (P = .05); however, these were comparable with the control group (P > .05). Regression analysis showed significant association of bleeding on probing with Gingival Index, clinical attachment level, and hsCRP (P = .05). Conclusions: CPA/EE combination does not influence the periodontal and systemic inflammatory status in PCOS females, as similar levels of local and systemic inflammation were observed in CPA/EE consumers compared with PCOS females not on medication. However, it might play a role in increasing gingival thickness and keratinized tissue width in these patients. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) forms the cornerstone in the treatment of advanced prostate cancer. However, by suppressing testosterone ADT results in a decrease of skeletal muscle mass. In this narrative review, we explore the magnitude and mechanisms of ADT-induced muscle mass loss and the consequences for muscle strength and physical performance. Subsequently, we elucidate the effectiveness of supervised resistance exercise training as a means to mitigate these adverse effects. Literature shows that resistance exercise training can effectively counteract ADT-induced loss of appendicular lean body mass and decline in muscle strength, while the effect on physical performances is inconclusive. As resistance exercise training is feasible and can be safely implemented during ADT (with special attention for patients with bone metastases), it should be incorporated in standard clinical care for prostate cancer patients (starting) with ADT. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease, affecting approximately one-fourth of adults worldwide, and is the leading cause of liver-related morbidity and mortality. MASLD is a sex-dimorphic disease, with a general higher prevalence in men. Women in fertile age exhibit a lower risk of MASLD than men. However, after menopause, their prevalence of MASLD becomes comparable to that of men. A complex interaction of gender-specific factors contributes to MASLD varying prevalence and severity. Sex is rarely considered as a biological variable in preclinical and clinical studies of MASLD. Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic liver condition. MASLD is a sexually dimorphic condition, with its development and progression influenced by sex chromosomes and hormones. Estrogens typically protect against, whereas androgens promote, MASLD. Therapeutic approaches for a sex-specific personalized medicine include estrogen replacement, androgen blockers, and novel drugs targeting hormonal pathways. However, the interactions between hormonal factors and inherited genetic variation impacts MASLD risk, necessitating more tailored therapies. Understanding sex disparities and the role of estrogens could improve MASLD interventions and management, whereas clinical trials addressing sex differences are crucial for advancing personalized treatment. This review explores the underappreciated impact of sexual dimorphism in MASLD and discusses the potential therapeutic application of sex-related hormones. [ABSTRACT FROM AUTHOR]

Deutenzalutamide is a new molecular entity androgen receptor antagonist. The primary aim of this study was to develop a population pharmacokinetic model of deutenzalutamide and evaluate effects of intrinsic and extrinsic factors on pharmacokinetics. A nonlinear mixed‐effects modeling approach was performed to develop the population pharmacokinetic of deutenzalutamide using data from 1 Phase I trial of deutenzalutamide. Goodness‐of‐fit plots, prediction‐corrected visual predictive check, and bootstrap analysis were carried out to evaluate the final model. Simulation for the developed model was used to evaluate the covariate effects on the pharmacokinetics of deutenzalutamide. A 2‐compartment model with first‐order absorption and elimination from the central compartment was established for deutenzalutamide. The final covariate included body weight on peripheral compartment volume. This is the first research developing the population pharmacokinetic model of deutenzalutamide in patients with metastatic castration‐resistant prostate cancer, and it is expected to support the future clinical administration of deutenzalutamide. [ABSTRACT FROM AUTHOR]

Breast cancer, an exceptionally hormone-dependent tumor, exhibits a diverse clinical profile. Its therapeutic categorization relies on the expression of key receptors, namely, estrogen receptor (ER), progesterone receptor (PR), and Her2neu. The androgen receptor (AR), a member of the nuclear receptor superfamily, is a biomarker gaining attention in breast cancer research, particularly for triple-negative breast cancers. We conducted an analysis of AR expression in 113 primary breast cancer cases, using a cutoff criterion of ≥ 10% tumor cell positivity. ER, PR, and Her2neu statuses were determined based on the 2023 ASCO-CAP criteria. AR expression was then correlated with various clinicopathological factors, including age, menopausal status, centricity, histological type, grade, tumor size, nodal status, lymphovascular and perineural invasion, and ER, PR, and HER2neu statuses. Among the 113 cases, 57 (50.4%) showed positive AR expression. No statistically significant associations were found between AR expression and age, menopausal status, histological type, histological grade, nodal status, or ER and PR expression. Notably, all multicentric tumors (n = 7, 100%) were AR negative. AR expression was linked to smaller tumor sizes. Positive AR cases exhibited an association with Her2neu overexpression, particularly in ER and PR-negative tumors. Of note, 35% of triple-negative tumors displayed AR positivity. AR emerges as a promising marker in breast cancers, particularly in triple-negative cases. Larger-scale studies are warranted to comprehensively assess the relationship between AR expression and histopathological parameters, as well as other immunohistochemical markers. [ABSTRACT FROM AUTHOR]

Androgens like testosterone and dihydrotestosterone are essential for the growth and development of the prostate gland. Androgenic receptors are overexpressed, which promotes the progression of prostate cancer; therefore, androgenic receptors are a key target in the therapy of prostate cancer. Enzalutamide is used to treat prostate cancer; however, it also causes toxicities such as cardiovascular toxicity, acute myocarditis, hypertension, and seizures. The objective of this research was to create novel and safer analogues of enzalutamide, followed by the prediction of the pharmacokinetic and toxicity characteristics of these enzalutamide analogues. Molecular docking studies of analogues were also done to guess how ligands will work biologically in treating prostate cancer. A total of 195 analogues were generated, and among them, 23 bioisosteres were selected for further pharmacokinetic, toxicological screening and docking studies. The predicted physical-chemical, medicinal, and ADMET characteristics of the designed bioisosteres were optimal to good compared to enzalutamide. Additionally, the drug likeness and drug score of analogues were superior to enzalutamide. According to docking studies of analogues, EZ12, EZ8, and EZ10 formed hydrogen bonds of SER778 with replaceable amide groups in enzalutamide molecules. SER778 residue may be responsible for antagonistic activity towards androgen receptors. Based on the results of the ADMET, drug likeness, drug score, and docking study of designed enzalutamide analogues, the ligands EZ12, EZ8, and EZ10 could be used to find more possible antiandrogen drugs that could be used to treat prostate cancer. [ABSTRACT FROM AUTHOR]

Background The use of androgen biosynthesis and second-generation androgen receptor inhibitors for advanced prostate cancer is increasing. Because these therapies alter the androgen pathway, they have been associated with cardiometabolic and neurocognitive toxicities. Although their safety profiles have been assessed in clinical trials, real-world data are limited. Methods A 20% sample of national Medicare claims was used to perform a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with androgen biosynthesis (ie, abiraterone) and second-generation androgen receptor inhibitors between 2012 and 2019. Outcomes were assessed after the first fill of either class of drug for the 12-month period after starting therapy. The primary outcome was a hospital admission or emergency department visit for a cardiometabolic event. Secondary outcomes included neurocognitive events and fractures. Multivariable regression was used to assess the association between the class of drug and occurrence of an adverse event. Results There were 3488 (60%) men started on an androgen biosynthesis inhibitor and 2361 (40%) started on an androgen receptor inhibitor for the first time. Cardiometabolic adverse events were more common in men managed with androgen biosynthesis inhibitor (9.2% vs 7.5%, P  = .027). No difference between androgen biosynthesis and androgen receptor inhibitors was observed for neurocognitive events (3.3% vs 3.4%, respectively; P  = .71) or fractures (4.2% vs 3.6%, respectively; P  = .26). Conclusions Men with advanced prostate cancer initiating an androgen biosynthesis inhibitor for the first time more commonly had cardiometabolic events than those started on androgen receptor inhibitors. Neurocognitive events and fractures did not differ by drug class. [ABSTRACT FROM AUTHOR]

Summary: Androgen Deprivation Therapy (ADT) increases long-term fracture risk in prostate cancer. Our study showed a higher fracture risk within six months of ADT use, and current use was associated with a higher risk of fragility fractures. Attention is needed for the prevention of fragility fractures at the start of ADT. Purpose: Androgen Deprivation Therapy (ADT) is known to increase long-term fracture risk in men with prostate cancer (PCa), although the risk of fragility fractures remains unclear. This study aims to evaluate the risk of fragility and malignancy-related fractures in men with PCa treated with ADT. Methods: We conducted a retrospective cohort study of men with PCa. Follow-up time was divided into 30-day intervals and exposure (current, past, or no-ADT use). Current ADT use was stratified by duration of ADT use (≤ 182 days, 183–730 days, and > 730 days). Cause-specific Cox proportional hazard models were used to estimate the risk of fractures. Results: We included 471 patients (mean age 70.5 (± 8.3) years). The mean follow-up time was 5.0 (± 1.7) years in patients who never started ADT, 3.4 (± 2.3) years and 4.1 (± 2.0) years in patients who started ADT at baseline and during follow-up, respectively. In total, 60 patients had a fracture, 48 (80%) fragility, and 12 (20%) malignancy-related fractures. Current ADT use was associated with a higher risk of all fractures (HR 5.10, 95% CI 2.34–11.13) and fragility fractures (HR 3.61, 95% CI 1.57–8.30). The association with malignancy-related fractures could not be studied due to no events during no-ADT use. There was an increased risk of all fractures with longer duration of ADT use. Conclusions: Current ADT use was associated with a higher risk of fragility fractures than no-ADT use. A higher fracture risk was observed within the first six months of ADT use and persisted for longer durations. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study. [ABSTRACT FROM AUTHOR]

Simple Summary: The current real-world study suggests that important differences exist in patients progressing to mCRPC. Specifically, we found that a proportion of over 20% of patients progress without a PSA level rise, emphasizing the importance of regular staging intervals. Moreover, we found that patients with worse PSA responses are at higher risk for biochemical progression, emphasizing the need for regular PSA check-ups and kinetic measurements. However, no differences in PFS and OS outcomes between these patients were observed. Finally, staging with PSMA-PET/CT might provide better PFS and OS, relative to conventionally staged mCRPC patients. However, this observation may be substantially influenced by the detection of earlier disease progression and the possibility of treatment in patients with a lower metastatic burden, as well as more contemporary patients with better treatment options. Background/Objectives: Progression to metastatic castration-resistant prostate cancer (mCRPC) is defined either biochemically, radiographically or both. Moreover, staging for mCRPC can be performed either conventionally or with molecular imaging such as prostate-specific membrane antigen computer tomography (PSMA-PET/CT). Methods: We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to compare progression-free (PFS) and overall survival (OS) outcomes regarding the cause of castration resistance and the staging modality used. Results: Overall, 35% progressed to mCRPC biochemically vs. 23% radiographically vs. 42% biochemically + radiographically. The PSA nadir in mHSPC (1.4 vs. 0.4 vs. 0.8 ng/mL) and PSA level at mCRPC progression (15 vs. 2 vs. 21 ng/mL, both p ≤ 0.01) were significantly higher for biochemical vs. radiographic vs. both progressed patients. In PFS and OS analyses, no significant differences were observed among all three compared groups. In the comparison of the staging used for progression to mCRPC, 67% received conventional vs. 33% PSMA-PET/CT, with higher metastatic burden in mHSPC and osseous lesions in mCRPC for conventionally staged patients (both p < 0.01). In PFS (15.3 vs. 10.1 months, hazard ratio [HR]: 0.75) and OS analyses (52.6 vs. 34.3 months, HR: 0.61, both p < 0.05), PSMA-PET/CT harbored better prognosis; however, this did not hold after multivariable adjustment. Similar results were observed for further analyses in second- and third-line mCRPC or patients with a PSA level of ≥2 ng/mL. Conclusions: The cause of progression to mCRPC seems not to influence cancer-control outcomes, despite important baseline tumor characteristic differences. The PSMA-PET/CT staging modality might be associated with better PFS and OS outcomes, possibly due to its more sensitive detection of progression or new metastatic lesions. [ABSTRACT FROM AUTHOR]

Introduction: Abiraterone and enzalutamide are two androgen receptor pathway inhibitors approved, among others, for the treatment of metastatic castration-resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based regimen. Although hematological effects, especially neutropenia, are one of the main complications of other oral antineoplastic drugs, these adverse effects are infrequent in the case of androgen receptor pathway inhibitors. Case report: We report the case of a patient diagnosed with metastatic castration-resistant prostate cancer who discontinued an androgen receptor pathway inhibitor due to drug-related grade 4 neutropenia. His control blood counts before enzalutamide starting were normal. After one month of treatment, he developed a grade 4 neutropenia, with complete neutrophil count recovery four weeks later. He underwent a bone marrow aspiration, which revealed normocelullar results, and enzalutamide was restarted. Three weeks later, the treatment was eventually discontinued due to neutropenia reappearance. Neutrophil count recovery was achieved one month later. Then, he started treatment with abiraterone, but two weeks later neutropenia reappeared. Abiraterone was withdrawn, and the patient recovered from neutropenia 2 weeks later. Management and outcomes: This case exposes not only the occurrence of rare toxicity of two individual drugs but also the description of a probable drug-class adverse event not reported before. The patient recovered from neutropenia after the androgen receptor pathway inhibitor was withdrawn, thereby supporting the diagnosis of probable drug-induced neutropenia. Discussion: There is scarce evidence in the literature concerning androgen receptor pathway inhibitor-related neutropenia. However, its life-threatening potential cannot be ignored, so healthcare professionals should be warned of the possibility of the occurrence of such adverse reactions. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is most commonly diagnosed in males after the age of 55 years. These patients are also at risk for cardiovascular disease and venous thromboembolism requiring antithrombotic therapy. Prostate cancer treatments, such as androgen receptor axis-targeted therapies (ARATs, i.e., abiraterone acetate, apalutamide, darolutamide, and enzalutamide), may interact with common antithrombotic medications like warfarin, clopidogrel, and the direct oral anticoagulants. However, the data detailing the clinical outcomes of patients treated with these combinations are limited. We undertook a comprehensive review of the literature and modified Delphi process to enable development of an evidence-based consensus document for the co-prescribing of ARATs with antithrombotic medications. Our assessments relied heavily on pharmacokinetic data and extrapolation from drug interaction studies of similarly metabolized drugs, highlighting the need for more research into the clinical impact of drug interactions in prostate cancer patients. Nonetheless, we provide a practical framework to support clinicians in day-to-day therapeutic decision making. Background/Objectives: Abiraterone acetate, apalutamide, darolutamide, and enzalutamide, which make up the androgen receptor axis-targeted therapies (ARATs) drug class, are commonly used in the management of prostate cancer. Many patients on ARATs also receive oral antithrombotic therapy (i.e., anticoagulants or antiplatelets). The concomitant use of ARATs and antithrombotic therapies creates the potential for clinically relevant drug–drug interactions, but the literature regarding the actual consequences of these interactions, and guidance for co-prescribing, is limited. We assembled a multidisciplinary panel of experts and provided them with clinical information derived from a comprehensive literature review regarding the drug–drug interactions between ARATs and antithrombotic therapies. Methods: A three-stage modified electronic Delphi process was used to gather and consolidate opinions from the panel. Each stage consisted of up to three rounds of voting to achieve consensus on which ARAT/antithrombotic therapy drug pairs warrant attention, the possible clinical consequences of drug–drug interactions, and suggested actions for management. Results: The panel achieved consensus to avoid 11 ARAT/antithrombotic therapy drug pairs and modify therapy for eight pairs. Assessments relied heavily on pharmacokinetic data and extrapolation from drug–drug interaction studies of similarly metabolized drugs. Conclusions: This e-Delphi process highlights the need for further research into the clinical impact of ARAT/antithrombotic drug interactions. Nonetheless, the suggested actions aim to provide clinicians with a practical framework for therapeutic decision making. [ABSTRACT FROM AUTHOR]

BACKGROUND: About one-quarter of patients with advanced prostate cancer have alterations in homologous recombination repair (HRR) genes. In a global phase 3 study, talazoparib plus enzalutamide significantly improved progression-free survival in patients with HRR-deficient metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVES: This article reviews the role of oncology nurses and advanced practice providers (APPs) in administering talazoparib plus enzalutamide in patients with mCRPC. METHODS: This review and hypothetical case study illustrate the role of oncology nurses and APPs in the administration of talazoparib plus enzalutamide and the management of adverse events to ensure safe and effective use in clinical practice. FINDINGS: Oncology nurses and APPs play an important role in the dosing and administration of talazoparib plus enzalutamide and can recognize and manage adverse events in patients with HRR-deficient mCRPC. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of herbal products, one component of the growing field of integrative cancer care, is a common yet controversial practice. OBJECTIVES: This article distinguishes nursing issues specific to patient safety when herbal products are used during cancer treatment and identifies available evidence-based resources to enhance patient and professional comprehension. METHODS: PubMed®, CINAHL®, and Google Scholar™ databases were searched for literature published between 2018 and 2024 specific to the clinical sequelae of the use of herbal products and their interactions with antineoplastic drugs, as well as patient and healthcare providers' perceptions of efficacy and safety. METHODS: PubMed®, CINAHL®, and Google Scholar™ databases were searched for literature published between 2018 and 2024 specific to the clinical sequelae of the use of herbal products and their interactions with antineoplastic drugs, as well as patient and healthcare providers' perceptions of efficacy and safety. [ABSTRACT FROM AUTHOR]

Physical activity (PA) is beneficial for both the physical and psychological health of prostate cancer (PCa) survivors. This study identified and examined motives for PA in a cross-section of PCa survivors, including both men in remission and those receiving treatment in the form of androgen deprivation therapy (ADT). Sixteen PCa survivors from Auckland, New Zealand were individually interviewed. Data were analyzed using an inductive thematic approach. Both groups of men were motivated to engage in PA post-diagnosis to obtain and experience the physical, mental, and cognitive health-related benefits associated with regular PA engagement. Past history of PA was also identified as a motive for current PA for men in remission. These findings provide important insight into how PCa survivors perceive the benefits of PA as a part of their cancer survivorship. Healthcare practitioners, exercise physiologists, and cancer support organizations can use this information to further improve PCa survivors' quality of life and overall cancer survivorship by better promoting PA to these individuals. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), as a novel endocrine therapy, has been investigated in patients with metastatic castration-resistant prostate cancer (mCRPC) in recent years. Multiple large-scale clinical trials have consistently demonstrated that various PARP inhibitors, including olaparib, rucaparib, niraparib, and talazoparib, confer longer radiographic progression-free survival (rPFS) compared to new hormonal agents (NHA) in mCRPC patients with homologous recombination deficiency (HRD). Moreover, the incidence of grade 3 and above adverse events did not significantly increase. Additionally, when combined with androgen receptor signaling inhibitors (ARSI), olaparib, niraparib, and talazoparib have shown significant extension of rPFS but also an increased occurrence of serious adverse events in HRD-positive patients. Only PROpel yielded positive results among the homologous recombination repair (HRR) mutation negative population. Therefore, it remains uncertain whether ARSI-PARPi combination therapy should be considered as first-line treatment for mCRPC patients without HRR mutations. In this review article, we aim to elucidate the necessity and feasibility of combination therapy versus monotherapy specifically within the HRR mutant population while exploring its potential applicability to other non-HRR mutant subtypes. Furthermore, we conducted a comprehensive search on registered clinical trials at present to summarize the research progress of PARP inhibitors in prostate cancer patients at different disease stages. [ABSTRACT FROM AUTHOR]

BACKGROUND. Metastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3β-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes. METHODS. Our prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes. RESULTS. Patients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide. CONCLUSION. These data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible. FUNDING. National Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council. [ABSTRACT FROM AUTHOR]

Simple Summary: Upfront novel androgen receptor signaling inhibitors (ARSIs) are the first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). However, there are a certain number of cases in which androgen deprivation therapy (ADT) is more effective in patients of Asian descent. If we can identify patients who show a marked response to ADT within 12 weeks after ADT, which is the inclusion criterion for upfront ARSI clinical trials, it would be valuable from an economic standpoint. A total of 218 patients who received ADT treatment at Kanazawa University Hospital between 2000 and 2020 were included in this study. Multivariate analysis revealed that a decrease in PSA levels of <95% at 12 weeks after ADT initiation was a predictor of short time to castration resistance (TTCR) in low-risk patients. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs, based on the rate of PSA reduction at 12 weeks. Background: The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. Methods: A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan–Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. Results: The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. Conclusion: The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w. [ABSTRACT FROM AUTHOR]

Gender‐affirming hormone therapy (GAHT) is used by many transgender and gender‐diverse adults to align physical characteristics with their gender identity, reduce gender incongruence and improve psychological functioning. This narrative review provides an overview of the initiation and monitoring of GAHT in an Australian context. Trans individuals treated with testosterone typically receive standard testosterone doses and formulations recommended for cisgender men, whereas those receiving estradiol GAHT are typically treated with estradiol in combination with an anti‐androgen in those without orchidectomy. Proactive monitoring and mitigation of cardiovascular risk factors is pertinent in all transgender and gender‐diverse adults and bone health is an important consideration in those using estradiol GAHT. [ABSTRACT FROM AUTHOR]

To assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA). This phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression. All patients received SBRT to the OPD site(s) and continued the current ARTA. Patients received 30 Gy in 5 fractions (alternate days) to the OPD site. The primary endpoint of the trial is to assess if SBRT to OPD sites results in progression free survival of >6 months. The primary endpoint for this toxicity analysis is the rate of grade 3 or higher adverse events at any timepoint up to 6 months after SBRT. Secondary endpoints included comparing pre- and post-SBRT patient-related outcomes reported using visual analogue scale scores and EQ-5D health questionnaire. Forty enrolled patients had at least 6 months of follow-up at the time of analysis. Grade 3 or higher toxicity from any cause recorded using common terminology criteria for adverse events and radiation therapy oncology group was found in 8/40 (20%) of patients, but only 1/40 (2.5%) was deemed possibly related to SBRT. There was no significant difference in mean EQ5D visual analogue scale score from baseline to each timepoint after SBRT (p = 0.449). In this prospective phase II clinical trial for OPD whilst on ARTA in the CRPC setting, we report low grade ≥ 3 toxicity after SBRT. There is no discernible change in patient-reported quality of life due to SBRT treatment. The final results of progression-free survival and toxicity of SBRT treatment will be reported once further follow-up is complete. • Stereotactic radiotherapy to oligoprogressive disease in metastatic prostate cancer patients on targeted agents is feasible. • Stereotactic body radiotherapy is well tolerated in patients with castrate-resistant prostate cancer. • There is minimal treatment-related effect on quality of life and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

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PURPOSE: Androgen receptor pathway inhibitors (ARPIs) are widely prescribed in metastatic castration-resistant prostate cancer (mCRPC). Real-world frequencies and potential impacts of comorbidities and concomitant medication (conmed) interactions with ARPIs are not well described. METHODS: Patients receiving ARPIs for mCRPC were identified from the electronic Prostate Cancer Australian Database (ePAD). Demographics, clinicopathologic characteristics, and outcome data were extracted. Conmeds and comorbidities were collected from medical records. Potential interacting comorbidities were defined from trial and post-trial data. Clinically significant drug-drug interactions (DDIs) were identified using UpToDate Lexicomp and Stockley's databases. Patient characteristics, comorbidity interactions, DDIs, and outcomes were analyzed. RESULTS: Two hundred thirty-five patients received first- or second-line ARPIs for mCRPC from 2012 to 2021, with a median follow-up of 27 months. One hundred sixteen received abiraterone acetate (AAP) and 135 received enzalutamide (ENZ). The median age was 74 years, and the median number of conmeds was 4. Clinically significant DDIs occurred in 55 (47%) AAP patients and 90 (67%) ENZ patients. Only 5% of DDIs were predicted to affect ARPI pharmacokinetics (PK) or pharmacodynamics, whereas 95% were predicted to impact conmed PK or increase toxicity risk. In patients receiving ENZ, DDIs were associated with lower PSA50 (50% v 74%, P =.04) and poorer overall survival (28 v 45 months, P =.04), although statistical significance was not maintained on multivariate analysis. No significant survival differences were seen with DDIs in patients receiving AAP. Potential interactions between comorbidities and ARPI were present in 72% on AAP and 14% on ENZ with no significant associated survival differences. CONCLUSION: DDIs and drug-comorbidity interactions in real-world patients receiving ARPIs for mCRPC are common and may affect outcomes. Ongoing clinician education regarding DDIs is necessary to optimize patient outcomes. Drug-drug interactions between conmeds and ENZ or AA were common and impacted outcomes in #ePAD real-world mCRPC pts. [ABSTRACT FROM AUTHOR]

This study was conducted to provide evidence, using in vitro and in silico testing methods, regarding the adverse effects of iprodione, a representative dichlorophenyl dicarboxamide fungicide, on the endocrine system. In the present study, we used the HeLa9903 stably transfected transactivation assay (OECD TG 455), 22Rv1/MMTV_GR‒KO androgen receptor transcriptional activation assay (OECD TG 458), and toxicity prediction using VEGA QSAR. Our results showed that iprodione had no estrogen receptor antagonistic or androgen receptor agonistic effects; however, iprodione was determined to be an estrogen receptor agonist (log PC10 value is less than − 9) and androgen receptor antagonist (log IC30 value is − 4.58) without intrinsic toxicity against the human cell lines used in this study. VEGA QSAR was used to evaluate five substances with structures similar to that of iprodione. Among them, four chemicals were found to have positive androgen receptor and aromatase activities and have been observed to be developmental toxicants. These results suggest that iprodione regulates steroid hormone receptor interactions and is a potential reproductive toxicant. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the second most common cancer among males and is a significant cause of morbidity and mortality. The chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) are expressed in prostate cancer but their prognostic value is unclear. This study investigated CCL2 and CCR2 as prognostic biomarkers in locally advanced prostate cancer using the large TROG 03.04 RADAR clinical trial cohort. The results demonstrate that despite being expressed in prostate tumours, CCR2 and CCL2 have no prognostic value in the disease. This study investigated the prognostic value of the chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) expression in locally advanced prostate cancer treated with radiotherapy and androgen deprivation using the 10-year outcome data from the TROG 03.04 RADAR clinical trial. CCL2 and CCR2 protein expression in prostate cancer biopsies at the time of diagnosis were quantified by immunohistochemistry and digital quantification. CCR2 protein expression was detected in prostate cancer cells and was associated with prostate-specific antigen serum concentration (p = 0.045). However, neither CCL2 nor CCR2 tissue expression could predict prostate cancer progression, or other clinicopathological parameters including perineural invasion and patient outcome. In serum samples, CCL2 concentration at the time of diagnosis, as assayed by enzyme-linked immunosorbent assay, was significantly higher in patients with prostate cancer compared with benign prostatic hyperplasia (median difference 0.22 ng/mL, 95% CI, 0.17–0.30) (p < 0.0001) and normal controls (median difference 0.13 ng/mL, 95% CI, 0.13–0.17) (p < 0.0001). However, circulating CCL2 was not statistically significant as a predictor of disease progression and patient outcome. In conclusion, this study shows that although CCL2 and CCR2 are expressed in prostate cancer, with an increased level of CCL2 in the serum, neither CCL2 nor CCR2 expression has a clinical prognostic value in locally advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Castration-resistant prostate cancer (CRPC) resists standard therapies, partly due to the androgen receptor variant AR-V7. Conventional treatments like chemotherapy and radiation have limited success and significant side effects. Natural compounds from herbal medicine offer promise as complementary therapies. This review examines how these natural compounds can improve treatment outcomes and reduce side effects, presenting a safer and more effective approach to managing CRPC and overcoming resistance to conventional therapies. Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, androgen receptor blockers, radiation therapy, immune therapy, and PARP inhibitors, often come with substantial side effects and limited efficacy. Natural compounds, particularly those derived from herbal medicine, have garnered increasing interest as adjunctive therapeutic agents against CRPC. This review explores the role of AR-V7 in CRPC and highlights the promising benefits of natural compounds as complementary treatments to conventional drugs in reducing CRPC and overcoming therapeutic resistance. We delve into the mechanisms of action underlying the anti-CRPC effects of natural compounds, showcasing their potential to enhance therapeutic outcomes while mitigating the side effects associated with conventional therapies. The exploration of natural compounds offers promising avenues for developing novel treatment strategies that enhance therapeutic outcomes and reduce the adverse effects of conventional CRPC therapies. These compounds provide a safer, more effective approach to managing CRPC, representing a significant advancement in improving patient care. [ABSTRACT FROM AUTHOR]

Simple Summary: Men with prostate cancer undergoing Androgen Deprivation Therapy (ADT) have an increased risk of fractures. Despite this risk, fracture risk assessment is often not systematically applied. To address this issue, a care pathway for preventing fractures in these patients was developed. A multidisciplinary working group designed this pathway based on Dutch guidelines for prostate cancer, osteoporosis and fracture prevention and a thorough literature review. The care pathway includes five steps: case finding, fracture risk assessment, bone mineral density testing, vertebral fracture assessment, differential diagnosis, treatment, and annual follow-up. This pathway focuses on a patient-centered approach and early preventive measures. The ongoing implementation and evaluation aim to enhance fracture preventive care for men with prostate cancer starting ADT. Fracture risk is increased in men with prostate cancer (PCa) receiving Androgen Deprivation Therapy (ADT). However, routine assessment of fracture risk is often not systematically applied. We aimed to establish a comprehensive care pathway for fracture prevention in men with PCa starting ADT. Therefore, a multidisciplinary working group designed and implemented a care pathway using the 'Knowledge to Action' framework, based on current Dutch guidelines for PCa, osteoporosis and fracture prevention, and an extensive literature review of other guidelines. The pathway was developed according to a five-step clinical approach including case finding, fracture risk assessment based on risk factors, bone mineral density test, vertebral fracture assessment, differential diagnosis, treatment, and annual follow-up. Our fracture prevention care pathway for patients with PCa at the time of ADT initiation was designed to promote a patient-centered, multidisciplinary approach to facilitate the implementation of early fracture prevention measures. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic prostate cancer (mPCa) is a leading cause of death primarily due to its resistance to treatments like enzalutamide. This study investigates how the protein HMGA2 contributes to this resistance. We found that cancer cells with high levels of HMGA2 became less sensitive to enzalutamide but not to another drug, alisertib. Interestingly, although these cells resisted enzalutamide, they did not show changes in a key prostate cancer protein called AR. Furthermore, a knockdown of HMGA2 sensitized the cells to both drugs. Clinically, 3% of patients showed changes in HMGA2, which were more common in cancers that had metastasized to bones, lymph nodes, and the liver. Our research suggests that HMGA2 could be used as a marker to predict enzalutamide resistance in mPCa cells. Additionally, alisertib may be an effective treatment for patients with high HMGA2 levels, offering a new potential therapeutic strategy for managing metastatic prostate cancer. Metastatic prostate cancer (mPCa) is a leading cause of mortality, partly due to its resistance to anti-androgens like enzalutamide. Snail can promote this resistance by increasing full-length AR and AR-V7. High Mobility Group AT-hook 2 (HMGA2), a DNA-binding protein upstream of Snail, is crucial in proliferation and epithelial–mesenchymal transition (EMT). This study examines HMGA2's role in enzalutamide resistance. LNCaP and 22Rv1 cells overexpressing wild-type HMGA2, but not truncated HMGA2, showed EMT. Both variants led to a decreased sensitivity to enzalutamide but not alisertib compared to Neo control cells. The overexpression of HMGA2 did not alter AR expression. Enzalutamide-resistant C4-2B cells (C4-2B MDVR) had higher HMGA2 and AR/AR variant expression than enzalutamide-sensitive C4-2B cells but remained sensitive to alisertib. The HMGA2 knockdown in C4-2B MDVR cells increased sensitivity to both enzalutamide and alisertib without changing AR expression. A clinical analysis via cBioPortal revealed HMGA2 alterations in 3% and AR alterations in 59% of patients. The HMGA2 changes were linked to treatments like enzalutamide, abiraterone, or alisertib, with amplifications more prevalent in bone, lymph node, and liver metastases. Conclusively, HMGA2 is a potential biomarker for enzalutamide resistance in mPCa, independent of Snail and AR signaling, and alisertib may be an effective treatment for mPCa that expresses HMGA2. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is a common and frequently undiagnosed female endocrine disorder that is associated with diverse symptoms and features, and an increased risk of long-term chronic diseases such as type 2 diabetes and cardiovascular disease. Pharmacotherapy for polycystic ovary syndrome should be directed at the key concerns of the individual patient. The combined oral contraceptive pill or metformin may be prescribed for irregular periods. The combined oral contraceptive pill is preferred over antiandrogens for treatment of hirsutism and acne. Metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m²). Inositol appears to have limited benefits for metabolic outcomes, although it is associated with fewer adverse effects than metformin. Modification of lifestyle factors is important as part of a holistic approach to managing polycystic ovary syndrome. Anti-obesity drugs may be considered for weight management in addition to lifestyle interventions. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most prevalent malignancies in men. In the United States, 1 in 8 men will be diagnosed with prostate cancer in their lifetime. Specifically, studies have delved into male subgroups that present a heightened risk for prostate cancer. Despite such high prevalence, prostate cancer can be heterogeneous and carry complexities that manifest differently between individuals. Metastatic hormone-sensitive prostate cancer (mHSPC) often has an abbreviated, aggressive disease course, and can have varying presentations with different molecular profiles that determine response/resistance to the approved treatments targeting the androgen-receptor pathway (eg, enzalutamide, apalutamide, darolutamide, and abiraterone acetate). We present a case of mHSPC quickly progressing to mCRPC, found to have microsatellite instability in mCRPC and excellent response to pembrolizumab, which raises the critical issues of early molecular testing and treatments personalized for the individual patient. [ABSTRACT FROM AUTHOR]

Background: Several randomized controlled trials (RCTs) demonstrated a significant survival benefit of novel treatment regimens compared with androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC), especially in high-volume disease (HVD, CHAARTED defined). As an influence on poor prognosis, the treatment for patients with HVD, especially visceral metastasis (VM) needed to be distinguished from mHSPC. This study was conducted to rank the treatment options for patients with HVD and VM, respectively, according to the latest data. Methods: We synthesized current evidence based on well-designed RCTs. Only phase III trials were included. A Bayesian network meta-analysis was conducted by using R-4.2.3, and the pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) with a 95% credible interval (CI) were calculated. Note that the definitions of PFS were various. The ranking plots were generated. OR of adverse events was also calculated and presented. This study was registered in the International Prospective Register of Systematic Reviews (CRD42023416334). Results: Eleven RCTs were included through Pubmed, Embase and Cochrane. In HVD patients, all combination therapies can improve OS and PFS. Among them, The HR for Darolutamide (Daro) + Docetaxel (Doc) + androgen deprivation therapy (ADT) was most significant over ADT in both OS and PFS (hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.39–0.63; HR: 0.25; 95% CI: 0.19–0.31). In patients with visceral metastasis, adding novel hormonal agents (NHAs) to ADT showed better survival outcome. But in analysis of treatment ranking, not alike the outcome of high-volume disease, Doc + ADT seems ranked higher than other NHA + ADT. Almost all combination therapies lead to more grade ≥ 3 adverse events. Conclusion: Triplet therapy achieved the best effect on both HVD and visceral metastasis with a tolerable adverse effect. In HVD, our findings demonstrated that any NHA, Docetaxel or triplet combination therapy was superior to ADT alone. Ranking of combination therapy differs between patients with HVD and visceral metastases. In patients with visceral metastasis, chemotherapy has a higher priority than novel hormonal agents. Abiraterone's efficacy ranked better compared to other NHAs but still worse than docetaxel. The sensitivity treatments of bicalutamide versus placebo lead to diversity of results. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the role of non-coding RNAs in resistance to the antiandrogen drug darolutamide in prostate cancer. RNA sequencing identified LOC730101 as a significantly elevated lncRNA in darolutamide-resistant cancer cells. Silencing LOC730101 reduced cancer cell proliferation, in support of its role in drug-resistant cancer growth. Elevated LOC730101 levels were observed in metastatic castration-resistant prostate cancer (CRPC) tumors compared to primary prostate tumors. LOC730101 modulates the expression of cell cycle genes by suppressing microRNA miR-1-3p. Hi-C sequencing revealed that the LOC730101 gene is situated within a dynamic topologically associating domain (TAD) that is activated in resistant cells. This study indicates that LOC730101 is crucial for darolutamide resistance and a potential target to overcome antiandrogen resistance in CRPC. Antiandrogen is part of the standard-of-care treatment option for metastatic prostate cancer. However, prostate cancers frequently relapse, and the underlying resistance mechanism remains incompletely understood. This study seeks to investigate whether long non-coding RNAs (lncRNAs) contribute to the resistance against the latest antiandrogen drug, darolutamide. Our RNA sequencing analysis revealed significant overexpression of LOC730101 in darolutamide-resistant cancer cells compared to the parental cells. Elevated LOC730101 levels were also observed in clinical samples of metastatic castration-resistant prostate cancer (CRPC) compared to primary prostate cancer samples. Silencing LOC730101 with siRNA significantly impaired the growth of darolutamide-resistant cells. Additional RNA sequencing analysis identified a set of genes regulated by LOC730101, including key players in the cell cycle regulatory pathway. We further demonstrated that LOC730101 promotes darolutamide resistance by competitively inhibiting microRNA miR-1-3p. Moreover, by Hi-C sequencing, we found that LOC730101 is located in a topologically associating domain (TAD) that undergoes specific gene induction in darolutamide-resistant cells. Collectively, our study demonstrates the crucial role of the lncRNA LOC730101 in darolutamide resistance and its potential as a target for overcoming antiandrogen resistance in CRPC. [ABSTRACT FROM AUTHOR]

Simple Summary: In 2021, the randomized controlled trial VISION showed that prostate-specific membrane antigen (PSMA)-based third-line radioligand therapy as monotherapy for patients with metastatic castration-resistant prostate cancer with positive lesions on PSMA PET/CT increases overall survival relative to the comparator treatment. The good results have inspired new trials. Our review provides a comprehensive update on post-VISION trials on RLT. The results are promising and may expand the role of PSMA-based RLT in patients with prostate cancer. In 2021, two randomized controlled trials (RCTs), TheraP and VISION, demonstrated that 177Lu-PSMA-617 as monotherapy was more effective for the decline of PSA than the comparator third-line treatments. Methods: Our review summarizes new RCTs that add to the use of radioligand therapy (RLT) for patients with high-risk prostate cancer (PCa). Results: Four past and present RCTs included 1081 patients. An RCT, ENZA-p, studied first-line treatment of patients with metastatic castration-resistant PCa (mCRPC). A combination of enzalutamide (ENZA) and 177Lu-PSMA-617 gave longer progression-free survival than ENZA as monotherapy. Other RCTs of patients with mCRPC, including the PSMAfore, and SPLASH trials, showed 177Lu-PSMA-617 as second-line treatment gave better progression-free survival than androgen receptor pathway inhibitors (combined p value < 6.9 × 10−6). Conclusions: Patients with PCa gain if they are given PSMA-RLT early in the treatment of PCa and as part of combination therapies. [ABSTRACT FROM AUTHOR]

A new class of pyrazolylmethylene-2-thioxoimidazolidin-4-one derivatives 3a–p were rationally designed and synthesized with the aim of exploring their potential as treatments for prostate cancer. The synthesized compounds 3a–p were biologically analyzed for their anticancer effects against AR+LNCaP, AR-PC-3, and Wi38 cell lines. The observed IC50 values against AR+LNCaP ranged between 10.27 ± 0.14 and 109.72 ± 2.06 µM after 24 h of incubation. Compounds 3i–k, 3m, and 3o–p recorded IC50 values of 05.22 ± 0.12 to 11.75 ± 0.07 µM after 48 h incubation in the presence of 1 nM DHT, with higher selectivity towards AR+LNCaP. Moreover, compounds 3i and 3k significantly induced Caspase 3 accumulation, reduced DNA content at the various stages of the cell cycle, and ultimately caused AR+LNCaP cell growth arrest, as confirmed by cell apoptosis assays. These findings suggest that these analogues of androgen receptor blockers have promising potential for further investigation as effective treatments for prostate cancer. [ABSTRACT FROM AUTHOR]

Cyproterone acetate (CPA) and spironolactone (SPL) are different antiandrogens in gender-affirming hormone therapy (GAHT) for transgender women. Few studies have evaluated their efficacy and user satisfaction, especially among East Asians. This study aimed to evaluate these aspects in Chinese transgender women. Data were collected retrospectively from transgender women visiting the Peking University Third Hospital from 2012 to 2021. From 639 people identified as transgender women, 151 of them (80 using CPA and 71 using SPL, 16 to 40-year-old) under stable GAHT ≥6 months were enrolled. Total testosterone levels and visual analogue scale (VAS)-based satisfaction scores were evaluated. No difference was observed in age between the CPA and SPL groups (median [IQR], 22 [20–24] years and 23 [20–26] years, respectively). The duration of GAHT was longer in CPA group than in SPL group (18 [10–32] months vs. 12 [8–21] months, p = 0.009). Total testosterone levels were significantly lower with CPA treatment (25 mg/d) than with SPL treatment (100 mg/d) (median [IQR]: 0.7 [0.7–2.1] nmol/L vs. 13.0 [6.0–17.8] nmol/L, p < 0.001). The proportion of total testosterone levels reaching the recommended range was significantly higher in CPA group than in SPL group (75.0% vs. 11.3%, p < 0.001). VAS-based satisfaction scores for erection decreased and figure feminization were higher in CPA group than in SPL group, which remained unchanged after adjusting for age, treatment duration, estradiol dose, and comorbid mental disorders (p < 0.05). The prolactin levels were higher in CPA group than in SPL group (18.9 [11.8–28.1] ng/ml vs. 11.8 [7.9–18.4] ng/ml, p < 0.001). No severe safety events were reported in both groups. In Chinese transgender women, CPA was more effective than SPL in lowering testosterone levels. Additionally, VAS scores indicated greater satisfaction with erection decreased and figure feminization using CPA compared to SPL. [ABSTRACT FROM AUTHOR]

Background: Androgen blockers are an essential part of gender affirming care in post-pubertal transfeminine patients. Bicalutamide is a highly potent androgen receptor blocker that is used primarily in adults. We aimed to review our experience with the use of bicalutamide in transgender adolescents who were assigned male at birth. Methods: A retrospective review of medical records of transfeminine patients treated with bicalutamide during an 8-year period was conducted. Results: Forty patients, aged 15.5 ± 1.55 years were identified, of whom 21 (53%) were started on bicalutamide alone and 19 were started concurrently on estrogen. In patients on bicalutamide alone, 90.4% reported breast development at their first follow up visit, which occurred at a median of 7.1 months. Patients were treated for 29.4 ± 18.2 months. No episodes of liver toxicity related to bicalutamide were seen. Conclusions: Although these results are preliminary, bicalutamide appears to be a safe option for androgen blockade in transgender girls. [ABSTRACT FROM AUTHOR]

To study prostate specific membrane antigen – positron emission tomography (Ga68PSMA-PETCT) based patterns of relapse at biochemical failure (BCF) after prostate-only radiotherapy (PORT) in high-risk (HR) prostate cancer and its implications on pelvic contouring recommendations. Patients with clinico-radiological high-risk node-negative prostate cancer treated with curative PORT and androgen deprivation therapy (ADT), either within the POP-RT randomised trial or off trial, who underwent a Ga68PSMA-PETCT upon BCF were included. Patterns of regional and distant recurrence on Ga68PSMA-PETCT were studied. Pelvic nodal recurrences were mapped with reference to the superior border of pubic symphysis. Pelvic lymph nodal caudal border (PLN cb) recommendations in the published contouring guidelines (RTOG cb , GETUG cb , PIVOTAL cb , NRG cb , GFRU cb) were evaluated. Of the total 262 patients screened, 68 eligible patients were included (POP-RT trial 35 patients; off-trial 33 patients). Median follow-up was 91 months (IQR, 72–117) and median time to BCF was 65 months (IQR, 49–83). Regional and distant recurrence was seen in 31 (46%) and 31 (46%) patients, respectively. Of the nodal recurrences, nearly half (46%, 14/31) had no distant metastases and 64% (20/31) had a failure in the common iliac nodal region. The lower-most nodal recurrence was 20 mm cranial to the top of pubic symphysis (RTOG cb , GETUG cb , GFRU cb) and 10 mm cranial to the PIVOTAL cb. The PLN cb recommended by NRG guideline (NRG cb) had an inter-patient variability of 32 mm, ranging from 16 mm above to 16 mm below the top of pubic symphysis, and the lower most nodal recurrence ranged from 4 mm to 36 mm cranial to NRG cb. Pelvic failures accounted for a major proportion of recurrences after prostate-only radiotherapy, with the caudal most nodal recurrence being 20 mm cranial to the top of pubic symphysis. This could have implications in defining the caudal border of contouring recommendations. • Roughly half of men with localised HRCaP have pelvic failures post prostate-only RT. • Pelvic nodal lower-border definition lacks consensus across existing guidelines. • Caudal-most nodal failure was mapped 20 mm superior to the top of pubic symphysis. [ABSTRACT FROM AUTHOR]

Introduction: Combination of abiraterone with androgen deprivation therapy (ADT) has better survival outcomes than ADT alone in metastatic Hormone-sensitive prostate cancer (mHSPC) in the Western population. In this prospective (Clinical Trials Registry-India [CTRI] registered) observational study, we present the comparative oncological outcomes of ADT alone and ADT + abiraterone in Indian patients, which is not available currently. Methods: This study (CTRI-number-CTRI/2020/07/026545) included newly diagnosed mHSPC patients from January 2020 to June 2023 in a tertiary care hospital, urology department. Patients fulfilling inclusion criteria were advised ADT with abiraterone (A + ADT), and those not affording received ADT monotherapy (ADT). The primary endpoint was overall survival (OS). Secondary outcomes included prostate-specific antigen (PSA) decline >90%, radiographic progression-free survival (rPFS), and PSA progression-free survival (pPFS). Results: Out of278 patients with mHSPC, 163 patients were excluded and 115 were analyzed (ADT = 40 vs. A + ADT = 75). After a median follow-up of 20.3 months, 11 of 40 (27.5%) in ADT-only arm and 15 of 75 (20%) in ADT + abiraterone arm had died (Hazard-ratio of death 0.72; 95% confidence interval 0.68-0.88; P < 0.001). A PSA decline of >90% was seen in 85% in the ADT alone group and 93.3% in the ADT + abiraterone group. Significantly better outcomes of the ADT + abiraterone were seen in the secondary endpoints of rPFS (P < 0.001) and pPFS (P < 0.001). The OS benefit was 28% reduction in risk of death in our study versus 37% and 38% in STAMPEDE and LATITUDE, respectively. pPFS and rPFS were also poorer in Indian subsets. Conclusions: Abiraterone with ADT improves OS, PSA response, rPFS, and pPFS in the Indian population akin to the Western data but with poorer OS, rPFS, and PSA progression-free survival on comparison. [ABSTRACT FROM AUTHOR]

Antiandrogens have been used for the treatment of prostate cancer as a single agent or in combination with hormone deprivation therapy. New generation antiandrogens act like androgen receptor inhibitors (ARIs). Their binding complex blocks the pathways of cellular proliferation and differentiation of the prostate. Enzalutamide, apalutamide and darolutamide are the new ARIs that demonstrated acceptable tolerability and toxicity, both active in hormone-sensitive and castration-resistant prostate cancer (CRPC). There is no evidence of superiority of one drug over the other, therefore the therapeutic choice depends on the safety profile in relation to the individual patient, their comorbidities and clinical condition. ARIs have also shown promising results in association with new drugs that are active on patients with metastatic CRPC carrying the mutated breast cancer gene (BRCA). Before undergoing new antiandrogenic therapies, patients should be evaluated for cardiological and metabolic risk and possible drug interactions.

The UK prison system offers a medical treatment pathway for people suffering from problematic sexual arousal (PSA) who have committed a sexual offence(s). The two main medications are Anti-androgens (AAs) and Selective-Serotonin Reuptake Inhibitors (SSRIs). Currently, evidence of the effectiveness of SSRIs is not sufficiently robust for them to be licensed in the UK for that purpose. Instead, SSRIs are prescribed 'off-label', and physicians must adhere to additional obligations in prescribing them. Yet SSRIs have fewer side effects than AAs and may be a better treatment option for many patients. The present study examined the effectiveness of AAs and SSRIs in incarcerated individuals with PSA (n = 77); the unmedicated comparison group (n = 58) resided at the same prison which houses people convicted of a sexual offence. Both medicated groups demonstrated reduced levels of PSA 3 months post-baseline; the comparison group did not. The findings provide evidence for the effectiveness of SSRIs in reducing PSA. The authors argue a randomised control trial is required to underpin the use of SSRIs in treating PSA and (potentially) its subsequent licensing. The latter would enable wider prescription in prison and community and make a substantive contribution to the prevention of sexual abuse. [ABSTRACT FROM AUTHOR]

The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol. [ABSTRACT FROM AUTHOR]

The article focuses on the screening and management practices of specialists treating prostate cancer patients undergoing androgen deprivation therapy (ADT) regarding cardiac, bone, and metabolic health issues. The study reveals that specialized physicians generally feel unlikely to screen and manage metabolic and cardiac health but are more comfortable addressing bone health, suggesting a need for comprehensive management strategies to enhance patient care.

Simple Summary: This reassessment of the findings from our phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate–high-risk prostate cancer in the absence of androgen deprivation therapy due to patient refusal, with a median follow-up of 6.5 years. Our primary focus is on analyzing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade ≥ 2, both genitourinary and gastrointestinal. Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate–high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25–74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17–76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate–high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the most common cancer in American men, aside from skin cancer, and it is the second deadliest. For patients with advanced or metastatic disease, systemic therapies are warranted. The backbone of these systemic therapies is androgen deprivation therapy (ADT). While providing effective tumor control, ADT can have significant side effects, especially problematic for the many overweight or obese men who are at higher risk for aggressive cancer. Our review investigates how lifestyle changes, particularly a low- carbohydrate diet, might reduce the unwanted metabolic effects of ADT. We specifically discuss two clinical trials, Carbohydrate and Prostate Study 1 (CAPS1) and Carbohydrate and Prostate Study 2 (CAPS2), examining this diet's impact on metabolic issues and cancer progression. Additionally, we explore how ADT might influence metabolism, aiming to improve patient outcomes by balancing treatment efficacy with quality of life. Prostate cancer (PC) stands as the most frequently diagnosed non-skin cancer and ranks as the second highest cause of cancer-related deaths among men in the United States. For those facing non-metastatic PC necessitating intervention, solely local treatments may not suffice, leading to a possible transition toward systemic therapies, including androgen deprivation therapy (ADT), chemotherapy, and therapies targeting androgen. Yet, these systemic treatments often bring about considerable adverse effects. Additionally, it is observed that overweight men are at a higher risk of developing aggressive forms of PC, advancing to metastatic stages, and succumbing to the disease. Consequently, there is a pressing demand for new treatment options that carry fewer side effects and enhance the current standard treatments, particularly for the majority of American men who are overweight or obese. In this article, we will review the metabolic response to ADT and how lifestyle modulation can mitigate these ADT-associated metabolic responses with a particular focus on the two clinical trials, Carbohydrate and Prostate Study 1 (CAPS1) and Carbohydrate and Prostate Study 2 (CAPS2), which tested the effects of low-carbohydrate diets on the metabolic side effects of ADT and PC progression, respectively. Furthermore, we will summarize the findings of serum metabolomic studies to elucidate the potential mechanisms by which ADT and low-carbohydrate diets can affect the metabolic response to mitigate the metabolic side effects while maximizing therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) is standard, first-line therapy for many aspects of prostate cancer treatment. Although ADT can be an effective treatment to inhibit androgen-fueled cell growth in prostate cancer, suppression has significant side effects, including the development or exacerbation of underlying osteoporosis. Patients may be unaware of the adverse effects on bone health and muscle strength commonly associated with ADT. Practice standards require consistent screening of all patients with prostate cancer before ADT initiation to facilitate optimal baseline and subsequent osteoporosis management. [ABSTRACT FROM AUTHOR]

Adult acne is a chronic inflammatory disease of the pilosebaceous unit characterized by the excessive production of abnormal sebum favoring an imbalance of the skin microbiota and the hyperproliferation of Cutibacterium acnes and other virulent microbial strains, leading to an inflammatory environment, innate immunity overactivation, and keratinocyte hyperproliferation in hair follicles pores. Degraded keratinocytes plug the pores, consequently forming microcomedons, which can later evolve to papules, nodules, pustules and scars. Distinct from juvenile acne, in adult female acne (AFA) the symptomatology occurs or persists in postadolescence (after age 25). Although hyperandrogenism or the excessive sensitivity of androgen receptors are the main causes, AFA can be triggered by multiple factors, either including or not including androgen disturbances. The prevalence in adult women is 15–20%. Hyperandrogenism is present in 50% of cases; 70% of hyperandrogenism cases feature polycystic ovary syndrome (PCOS), a complex endocrine and metabolic condition. Genetic susceptibility occurs in 80% of acne cases, often with familial inheritance. Beyond classical stepwise therapeutic protocols (topical agents, isotretinoin, antibiotics, hormonal therapy with estrogens, progestins, spironolactone), novel approaches include the highly effective topical antiandrogen clascoterone, the management of insulin resistance by diet, exercise, stress avoidance, and adjuvant therapies such as berberine. Vaccines against the pathogenic proinflammatory C. acnes hyaluronidase A are in development. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, effective treatment for metastatic prostate cancer (PCa) remains a clinical challenge. Our previous study demonstrated that tumor suppressive miR-99b-5p negatively regulates the expression of androgen receptor (AR) and mTOR, potentially serving as a therapeutic agent for aggressive PCa. In this study, we show for the first time that combination of miR-99b-5p mimic and second-generation AR antagonist (such as enzalutamide or abiraterone) simultaneously targets AR and mTOR signaling, consequently inhibiting epithelial-mesenchymal transition (EMT) in PCa. This novel combination therapy may provide a unique opportunity for effectively suppressing EMT-mediated metastasis in aggressive PC, especially African American PCa and castration-resistant prostate cancer (CRPC). Prostate cancer (PCa) is the most frequently diagnosed cancer and second leading cause of cancer deaths among American men. Androgen deprivation therapy (ADT) has been systemically applied as a first-line therapy for PCa patients. Despite the initial responses, the majority of patients under ADT eventually experienced tumor progression to castration-resistant prostate cancer (CRPC), further leading to tumor metastasis to distant organs. Therefore, identifying the key molecular mechanisms underlying PCa progression remains crucial for the development of novel therapies for metastatic PCa. Previously, we identified that tumor-suppressive miR-99b-5p is frequently downregulated in aggressive African American (AA) PCa and European American (EA) CRPC, leading to upregulation of mTOR, androgen receptor (AR), and HIF-1α signaling. Given the fact that mTOR and HIF-1α signaling are critical upstream pathways that trigger the activation of epithelial–mesenchymal transition (EMT), we hypothesized that miR-99b-5p may play a critical functional role in regulating EMT-mediated PCa metastasis. To test this hypothesis, a series of cell biology, biochemical, and in vitro functional assays (wound healing, transwell migration, cell/ECM adhesion, and capillary-like tube formation assays) were performed to examine the effects of miR-99b-5p mimic on regulating EMT-mediated PCa metastasis processes. Our results have demonstrated that miR-99b-5p simultaneously targets MTOR and AR signaling, leading to upregulation of E-cadherin, downregulation of Snail/N-cadherin/Vimentin, and suppression of EMT-mediated PCa metastasis. MiR-99b-5p alone and in combination with enzalutamide or abiraterone significantly inhibits the EMT-mediated metastasis of AA PCa and EA CRPC. [ABSTRACT FROM AUTHOR]

Simple Summary: In this paper, we look at the role of artificial intelligence (AI) advancements in prostate cancer diagnosis and management. Specifically, we focus on magnetic resonance prostate reconstruction, prostate cancer detection/stratification/reconstruction, positron emission tomography/computed tomography, androgen deprivation therapy, and prostate biopsy. A total of 64 studies were included. Our results showed that deep learning AI models in prostate cancer diagnosis show promise but are not yet ready for clinical use due to variability in methods, labels, and evaluation criteria. Conducting additional research while acknowledging the limitations is crucial for reinforcing the utility and effectiveness of AI-based models in clinical settings. Background: The aim was to analyze the current state of deep learning (DL)-based prostate cancer (PCa) diagnosis with a focus on magnetic resonance (MR) prostate reconstruction; PCa detection/stratification/reconstruction; positron emission tomography/computed tomography (PET/CT); androgen deprivation therapy (ADT); prostate biopsy; associated challenges and their clinical implications. Methods: A search of the PubMed database was conducted based on the inclusion and exclusion criteria for the use of DL methods within the abovementioned areas. Results: A total of 784 articles were found, of which, 64 were included. Reconstruction of the prostate, the detection and stratification of prostate cancer, the reconstruction of prostate cancer, and diagnosis on PET/CT, ADT, and biopsy were analyzed in 21, 22, 6, 7, 2, and 6 studies, respectively. Among studies describing DL use for MR-based purposes, datasets with magnetic field power of 3 T, 1.5 T, and 3/1.5 T were used in 18/19/5, 0/1/0, and 3/2/1 studies, respectively, of 6/7 studies analyzing DL for PET/CT diagnosis which used data from a single institution. Among the radiotracers, [68Ga]Ga-PSMA-11, [18F]DCFPyl, and [18F]PSMA-1007 were used in 5, 1, and 1 study, respectively. Only two studies that analyzed DL in the context of DT met the inclusion criteria. Both were performed with a single-institution dataset with only manual labeling of training data. Three studies, each analyzing DL for prostate biopsy, were performed with single- and multi-institutional datasets. TeUS, TRUS, and MRI were used as input modalities in two, three, and one study, respectively. Conclusion: DL models in prostate cancer diagnosis show promise but are not yet ready for clinical use due to variability in methods, labels, and evaluation criteria. Conducting additional research while acknowledging all the limitations outlined is crucial for reinforcing the utility and effectiveness of DL-based models in clinical settings. [ABSTRACT FROM AUTHOR]