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Journal of Clinical Medicine Mar 2024(1) : Paraphilic disorders, marked by intense sexual fantasies and behaviors, present formidable challenges. This review addresses concerns fueled by scandals and child... (Review)
Review
(1) : Paraphilic disorders, marked by intense sexual fantasies and behaviors, present formidable challenges. This review addresses concerns fueled by scandals and child abuse. Emphasizing paraphilias' complexity, it systematically reviews the pharmacotherapy literature, aiming to enhance understanding and guide future research. (2) : A comprehensive search from 1990 to 2023 across major databases identified 28 relevant English-language studies. Inclusion criteria focused on adult pharmacotherapy for paraphilias, and results were evaluated using the Newcastle-Ottawa Scale. (3) : Synthesizing data from selected studies, diverse treatments such as SSRIs and antiandrogens were analyzed, revealing variable effectiveness and side effect profiles. Poor quality of the current literature has been reported. (4) : Highlighting the pivotal role of the serotonergic system, this review underscores the efficacy of SSRIs and androgen deprivation therapy. GnRH analog-associated side effects and the importance of a combined assessment approach are discussed. Critical insights contribute to understanding and ethical considerations in paraphilic disorders.
PubMed: 38541750
DOI: 10.3390/jcm13061524 -
Frontiers in Endocrinology 2023Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of direct comparison of the therapeutic effects and adverse events between the conventional ARI (bicalutamide) and three second-generation ARIs (enzalutamide, apalutamide and darolutamide).
METHODS
Our network meta-analysis evaluated therapeutic effects and adverse events of the conventional ARI (bicalutamide) and the second-generation ARIs in treating CRPC. We systematically searched the Pubmed, Cochrane library and Embase databases for studies published until October 2022 and only randomized clinical trials (RCTs) were included. The progression-free survival, prostate-specific antigen (PSA) progression-free survival, overall survival (PFS/PSA-PFS/OS), PSA response rate and relative adverse events (AEs) of CRPC patients were collected and synthesized. We then performed subgroup analysis. The non-metastatic and metastatic CRPC (nm/mCRPC) observations were analyzed separately. Data analyses were performed using R software (4.2.1) based on Bayesian framework.
RESULTS
6,993 subjects from seven eligible RCTs were analyzed. Enzalutamide, apalutamide and darolutamide were more effective than bicalutamide in treating CRPC, and the performance of darolutamide was slightly worse than the other two second-generation ARIs. Similar adverse events rate were observed among the second-generation ARIs and bicalutamide. Apalutamide showed a slightly higher rate of Grade 3+ AEs, percentages of AE-related drug withdrawals and AE-related mortality. Patients receiving enzalutamide had significantly higher rate of hypertension and fatigue. In subgroup analysis, enzalutamide showed better therapeutic effects compared with bicalutamide in both nmCRPC and mCRPC groups. In nmCRPC group, enzalutamide and apalutamide had more benefits on PFS and PSA-PFS compared with darolutamide. We displayed the probability ranking map of PFS, PSA-PFS, OS, time to cytotoxic chemotherapy, PSA response rate and relative AE outcomes.
CONCLUSION
The current network meta-analysis indicated that the second-generation ARIs were superior to the conventional ARI, bicalutamide. The three second-generation ARIs showed incomplete equivalence on CRPC treatment. The darolutamide was slightly less effective compared with enzalutamide and apalutamide. The adverse events of apalutamide were worse than the others, but no statistical significance was observed among these vital AEs. All ARIs were generally well-tolerated. These results may provide reference to clinical decision and further direct comparison trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022370842.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Prostate-Specific Antigen; Network Meta-Analysis; Treatment Outcome; Androgen Receptor Antagonists
PubMed: 36843606
DOI: 10.3389/fendo.2023.1131033 -
Frontiers in Pharmacology 2021Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and... (Review)
Review
Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and metastatic cancer. ADT is associated with numerous adverse effects derived from the pharmacological properties. Previous meta-analysis on fracture risk among ADT users possessed limited data without further subgroup analysis. Risk estimation of updated real-world evidence on ADT-related fracture remains unknown. To assess the risk of fracture and fracture requiring hospitalization associated with ADT among prostate cancer population on different disease conditions, treatment regimen, dosage level, fracture sites. The Cochrane Library, PubMed, and Embase databases were systematically screened for eligible cohort studies published from inception to March 2020. Two authors independently reviewed all the included studies. The risks of any fracture and of fracture requiring hospitalization were assessed using a random-effects model, following by leave-one-out, stratified, and sensitivity analyses. The Grading of Recommendations Assessments, Development and Evaluations (GRADE) system was used to grade the certainty of evidence. Sixteen eligible studies were included, and total population was 519,168 men. ADT use is associated with increasing fracture risk (OR, 1.39; 95% CI, 1.26-1.52) and fracture requiring hospitalization (OR, 1.55; 95% CI, 1.29-1.88). Stratified analysis revealed that high-dose ADT results in an elevated risk of fracture with little statistical heterogeneity, whereas sensitivity analysis restricted to adjust for additional factors indicated increased fracture risks for patients with unknown stage prostate cancer or with no restriction on age with minimal heterogeneity. The GRADE level of evidence was moderate for any fracture and low for fracture requiring hospitalization. Cumulative evidence supports the association of elevated fracture risk with ADT among patients with prostate cancer, including those with different disease conditions, treatment regimens, dose levels, and fracture sites. Further prospective trials with intact information on potential risk factors on fracture under ADT use are warranted to identify the risky population.
PubMed: 34421586
DOI: 10.3389/fphar.2021.652979 -
International Journal of Transgender... 2020Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone... (Review)
Review
BACKGROUND
Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy.
METHODS
We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence.
FINDINGS
We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas.
INTERPRETATION
Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.
PubMed: 34993517
DOI: 10.1080/15532739.2020.1819505 -
International Journal of Clinical... Jun 2024Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for... (Meta-Analysis)
Meta-Analysis
Impact of disease volume on survival efficacy of triplet therapy for metastatic hormone-sensitive prostate cancer: a systematic review, meta-analysis, and network meta-analysis.
BACKGROUND
Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear.
METHODS
We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist.
RESULTS
Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease.
CONCLUSIONS
Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.
Topics: Humans; Male; Androgen Antagonists; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Network Meta-Analysis; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Tumor Burden
PubMed: 38582807
DOI: 10.1007/s10147-024-02485-4 -
PloS One 2022Androgen deprivation therapy is a common treatment for prostate cancer. However, this therapy is associated with various adverse effects, such as increased body fat and... (Meta-Analysis)
Meta-Analysis
Androgen deprivation therapy is a common treatment for prostate cancer. However, this therapy is associated with various adverse effects, such as increased body fat and decreased bone mineral density. Exercise may be useful for ameliorating these adverse effects, although it is not completely effective. This review aimed to clarify how exercise interventions influenced body composition and bone mineral density and to explore the most effective exercise program among prostate cancer patients who received androgen deprivation therapy. We searched the PubMed, EMBASE, Web of Science, EBSCO, and Cochrane Library databases for reports of randomised controlled trials that were published until October 2021. All studies involved prostate cancer patients who received androgen deprivation therapy and completed aerobic exercise, resistance exercise, and/or impact exercise training. Outcomes were defined as lean body mass, body fat mass, body fat rate, regional and whole-body bone mineral density. Thirteen reports regarding 12 randomised clinical trials (715 participants) were included. Relative to the control group, exercise intervention provided a higher lean body mass (mean difference: 0.88, 95% confidence interval: 0.40 to 1.36, P<0.01), a lower body fat mass (mean difference: -0.60, 95% confidence interval: -1.10 to -0.10, P<0.05), and a lower body fat rate (mean difference: -0.93, 95% confidence interval: -1.39 to -0.47, P<0.01). Subgroup analyses revealed greater efficacy for exercise duration of ≥6 months (vs. <6 months) and exercise immediately after the therapy (vs. delayed exercise). No significant differences were observed in the bone mineral density outcomes. Exercise can help ameliorate the adverse effects of androgen deprivation therapy in body composition, with combination exercises including resistance exercise, 8-12 repetition maximum of resistance exercise intensity, prolonged exercise duration, and performing exercise immediately after therapy providing better amelioration. And the combination of resistance and impact exercise appears to be the best mode for improving the bone mineral density.
Topics: Adipose Tissue; Androgen Antagonists; Body Composition; Bone Density; Exercise Therapy; Humans; Male; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35167609
DOI: 10.1371/journal.pone.0263918 -
Asian Journal of Andrology 2021This study aimed to identify the pathological outcomes and survival benefits of neoadjuvant hormone therapy (NHT) combined with radical prostatectomy (RP) and... (Meta-Analysis)
Meta-Analysis
This study aimed to identify the pathological outcomes and survival benefits of neoadjuvant hormone therapy (NHT) combined with radical prostatectomy (RP) and radiotherapy (RT) administered to patients with high-risk prostate cancer (HRPCa). We searched PubMed, Embase, and the Cochrane Library for studies comparing NHT plus RP or RT with RP or RT alone, administered to patients with HRPCa. We used a random-effects model to compute risk estimates with 95% confidence intervals (CIs) and quantified heterogeneity using the I "2" statistic. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. We selected 16 studies. NHT before RP significantly decreased lymph node involvement (risk ratio [RR] = 0.69, 95% CI: 0.56-0.87) and increased the rates of pathological downstaging (RR = 2.62, 95% CI: 1.22-5.61) and organ-confinement (RR = 2.24, 95% CI: 1.54-3.25), but did not improve overall survival and biochemical progression-free survival (bPFS). The administration of NHT before RT to patients with HRPCa was associated with significant benefits for cancer-specific survival (hazard ratio [HR] = 0.51, 95% CI: 0.39-0.68), disease-free survival (HR = 0.51, 95% CI: 0.44-0.60), and bPFS (HR = 0.54, 95% CI: 0.46-0.64). Short-term NHT combined with RT administered to patients with HRPCa conferred significant improvements. Although the advantage of local control was observed when NHT was administered before RP, there was no significant survival benefit associated with HRPCa. Therefore, short-term NHT combined with RT is recommended for implementation in standard clinical practice but not for patients who undergo RP.
Topics: Androgen Antagonists; Hormone Replacement Therapy; Humans; Male; Neoadjuvant Therapy; Outcome Assessment, Health Care; Prostatectomy; Prostatic Neoplasms
PubMed: 33586699
DOI: 10.4103/aja.aja_96_20 -
International Journal of Clinical... Nov 2020Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However,... (Meta-Analysis)
Meta-Analysis
Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77-0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78-0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69-0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74-0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.
Topics: Androgen Receptor Antagonists; Antineoplastic Agents; Benzamides; Humans; Kallikreins; Male; Network Meta-Analysis; Nitriles; Phenylthiohydantoin; Progression-Free Survival; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Pyrazoles; Thiohydantoins; Treatment Outcome
PubMed: 32924096
DOI: 10.1007/s10147-020-01777-9 -
Current Oncology (Toronto, Ont.) Dec 2022In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway... (Meta-Analysis)
Meta-Analysis
Addition of New Androgen Receptor Pathway Inhibitors to Docetaxel and Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Metanalysis.
In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway inhibitors (ARPI) have been shown to improve overall survival (OS) compared to androgen deprivation therapy (ADT). Recent data could once again radically change mHSPC treatment. PEACE-1 and ARASENS trials demonstrated a survival benefit of the addition of ARPI to docetaxel and ADT combination (triplet therapy), compared to docetaxel and ADT. With multiple options to choose from, it is crucial to identify the patients who would benefit most from triplet therapy. In this meta-analysis, we evaluated the activity of the triplet therapy versus docetaxel plus ADT in mHSPC. A systematic review of PubMed/Medline, Embase, and the proceedings of major international meetings was performed. Five RCTs fulfilled the inclusion criteria. PEACE-1 and ARASENS studies reported disease-free survival (DFS) and OS. Post hoc analysis of three other trials evaluated the combination of ARPI, docetaxel and ADT. Globally, 2538 patients were included (1270 triplet therapy; 1268 docetaxel + ADT). Triplet therapy was associated with improved OS (hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.66-0.83, < 0.00001). A statistically significant benefit was shown in high-volume mHSPC patients (HR 0.76; 95% CI 0.59-0.97, = 0.03) and in patients with de novo metastatic disease (HR 0.73; 95% CI, 0.64-0.82, < 0.00001). The addition of ARPI to standard therapy was associated with DFS improvement (HR 0.41; 95% CI, 0.35-0.49, < 0.00001). This metanalysis shows a significant OS benefit from concomitant administration of ARPI, docetaxel and ADT in high volume and de novo mHSPC.
Topics: Humans; Male; Androgens; Docetaxel; Prostatic Neoplasms; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36547161
DOI: 10.3390/curroncol29120747 -
American Journal of Men's Health 2021Several studies reported the application of androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. (Meta-Analysis)
Meta-Analysis
CONTEXT
Several studies reported the application of androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation.
OBJECTIVE
To perform a systematic review and meta-analysis evaluating of endocrine therapy and radiotherapy in patients with biochemical recurrence after prostate cancer surgery. The primary end point was biochemical progression-free survival (bPFS). Secondary end point was overall survival (OS).
METHODS
A systematic review of PubMed/Medline, Embase, and Cochrane databases to identify relevant studies published in English up to March 2020. Twelve studies were selected for inclusion.
RESULTS
There were 11 studies included in the present study. Including two randomized controlled trials and nine cohort studies. The meta-analysis shows a significant bPFS benefit from androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. (hazard ratio [HR]: 0.57; 95% confidence interval CI, 0.52-0.63; .001). For patients with GS < 7 and low-risk patients, combined treatment can have a benefit for BPFs (HR: 0.53; 95% CI, 0.37-0.76; HR: 0.58; 95% CI, 0.36-0.93). Androgen deprivation therapy and radiotherapy in patients with biochemical recurrence was associated with a slightly OS improvement (HR: 0.73; 95% CI, 0.57-0.93; = 0.01).
CONCLUSIONS
Compared with salvage radiotherapy alone, This meta-analysis shows a significant bPFS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence after prostate cancer operation. And benefit more for high-risk groups. However, there was no significant benefit in group GS ≥ 8. It shows a slightly OS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence.
Topics: Androgen Antagonists; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy
PubMed: 34189987
DOI: 10.1177/15579883211024881