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European Urology Dec 2022Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide,... (Meta-Analysis)
Meta-Analysis Review
Androgen Receptor Signaling Inhibitors in Addition to Docetaxel with Androgen Deprivation Therapy for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Meta-analysis.
CONTEXT
Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide, darolutamide (DAR), and enzalutamide (ENZ), to docetaxel (DOC) and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
OBJECTIVE
To analyze the oncologic benefit of triplet combination therapies using ARSI + DOC + ADT, and comparing them with available treatment regimens in patients with mHSPC.
EVIDENCE ACQUISITION
Three databases and meetings abstracts were queried in April 2022 for RCTs analyzing patients treated with first-line combination systemic therapy for mHSPC. The primary interests of measure were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were conducted to assess the differential outcomes in patients with low- and high-volume disease as well as de novo and metachronous metastasis.
EVIDENCE SYNTHESIS
Overall, 11 RCTs were included for meta-analyses and network meta-analyses (NMAs). We found that the triplet combinations outperformed DOC + ADT in terms of OS (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.84) and PFS (pooled HR: 0.49, 95% CI: 0.42-0.58). There was no statistically significant difference between patients with low- and high-volume disease in terms of an OS benefit from adding an ARSI to DOC +ADT (both HR: 0.79; p = 1). Based on NMAs, triplet therapy also outperformed ARSI + ADT in terms of OS (DAR + DOC + ADT: pooled HR: 0.74, 95% CI: 0.55-0.99) and PFS (ABI + DOC + ADT: HR: 0.68, 95% CI: 0.51-0.91, and ENZ + DOC + ADT: HR: 0.70, 95% CI: 0.53-0.93). An analysis of treatment ranking among de novo mHSPC patients showed that triplet therapy had the highest likelihood of improved OS in patients with high-volume disease; however, doublet therapy using ARSI + ADT had the highest likelihood of improved OS in patients with low-volume disease.
CONCLUSIONS
We found that the triplet combination therapy improves survival endpoints in mHSPC patients compared with currently available doublet treatment regimens. Our findings need to be confirmed in further head-to-head trials with longer follow-up and among various patient populations.
PATIENT SUMMARY
Our study suggests that triplet therapy with androgen receptor signaling inhibitor, docetaxel, androgen deprivation therapy prolongs survival in patients with metastatic hormone-sensitive prostate cancer compared with the current standard doublet therapy.
Topics: Humans; Male; Docetaxel; Androgen Antagonists; Androgens; Receptors, Androgen; Antineoplastic Combined Chemotherapy Protocols; Prostatic Neoplasms
PubMed: 35995644
DOI: 10.1016/j.eururo.2022.08.002 -
Journal of Applied Physiology... Dec 2023Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher... (Meta-Analysis)
Meta-Analysis Review
Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.
Topics: Female; Humans; Contraceptives, Oral; Menstrual Cycle; Hormones; Progesterone; Hypertrophy
PubMed: 37823207
DOI: 10.1152/japplphysiol.00346.2023 -
Advances in Nutrition (Bethesda, Md.) Jun 2021Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk...
Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng and forskohlii root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made. This systematic review was registered at PROSPERO as CRD42020173623.
Topics: Humans; Male; Plant Extracts; Spices; Testosterone
PubMed: 33150931
DOI: 10.1093/advances/nmaa134 -
JAMA Oncology May 2023The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown.
OBJECTIVE
To assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups.
DATA SOURCES
For this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database's inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a "living" auto search was created with weekly updates to identify new evidence as it became available.
STUDY SELECTION
Phase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022.
MAIN OUTCOMES AND MEASURES
Outcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life.
RESULTS
This report included 10 RCTs with 11 043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO + docetaxel [D] + androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP + D + ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D + ADT) but not compared with API doublets. Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT.
CONCLUSIONS AND RELEVANCE
The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.
Topics: Aged; Humans; Male; Middle Aged; Androgen Antagonists; Androgens; Castration; Network Meta-Analysis; Prostatic Neoplasms; Quality of Life
PubMed: 36862387
DOI: 10.1001/jamaoncol.2022.7762 -
European Urology Oncology Dec 2022Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear.
OBJECTIVE
To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments.
EVIDENCE ACQUISITION
We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate.
EVIDENCE SYNTHESIS
Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (>60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (<40%) to be beneficial.
CONCLUSIONS
Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies.
PATIENT SUMMARY
We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.
Topics: Male; Humans; Docetaxel; Network Meta-Analysis; Androgens; Prostatic Neoplasms
PubMed: 35599144
DOI: 10.1016/j.euo.2022.04.007 -
Journal of Personalized Medicine Feb 2023Fenugreek extracts possess promising physiological and pharmacological properties in human and animal models. This review aims to provide a scientific and comprehensive... (Review)
Review
Fenugreek extracts possess promising physiological and pharmacological properties in human and animal models. This review aims to provide a scientific and comprehensive analysis of the literature on the effects of fenugreek extracts on muscle performance. An extensive online search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The main medical and scientific engines were searched for articles from May 1981 to May 2021 to capture all scientific studies focused on the effect of fenugreek on muscle and exercise or sport. Out of 81 studies acquired, six eligible randomized controlled trials (RCTs) were included in the qualitative analysis. Four RCTs observed that fenugreek supplementation had significantly improved muscle strength, repetitions to failure (muscle endurance), submaximal performance index, lean body mass, and reduced body fat. Among the remaining two trials, one reported the significant effect of fenugreek extracts on the rate of muscle glycogen resynthesis during post-exercise recovery; however, the other failed to do so. Those two trials were weak, with a minimal sample size (<10). Further, fenugreek glycoside supplementation with sapogenins and saponins reported substantial anabolic and androgenic activity, influencing testosterone levels and muscle performance. It was useful during eight weeks of resistance training without any clinical side effects. Fenugreek with creatine supplementation improved creatine uptake without the necessity of high carbohydrate intake. Hence, fenugreek extracts can be a helpful natural supplement and ergogenic aid for athletes. However, it is better to be aware of doping and liver and kidney damage before using the fenugreek supplement.
PubMed: 36983608
DOI: 10.3390/jpm13030427 -
JBRA Assisted Reproduction Aug 2022Infertility, defined as the inability to conceive after one year of intercourse without the use of contraception, affects 15% of couples. Many factors, such as... (Review)
Review
OBJECTIVE
Infertility, defined as the inability to conceive after one year of intercourse without the use of contraception, affects 15% of couples. Many factors, such as genitourinary tract infections, endocrine disorders, immunological factors and drug-related injuries, affect the male reproductive system and cause infertility. Due to men's fear of infertility, it is very important to pay attention to medicinal plants that are effective in male fertility. Therefore, the aim of this study was to evaluate the medicinal plants that affect sperm and testosterone production in men.
METHODS
In this review, we used the following search terms, consisting of herbal medicine, traditional medicine, traditional therapies, sperm, testosterone, testicles and Iran were used to retrieve the relevant articles published in the journals indexed in the Information Sciences Institute, Science Direct, PubMed, Scopus, PubMed Central and Scientific Information Databases. We searched and used papers published between 2000 and 2020. Then, we analyzed the eligible papers. We collected and analyzed 35 papers from the databases. We selected only the articles about herbs that affect sperm and testosterone production.
RESULTS
Based on the results, herbs Apium graveolens, Cinnamomum camphora, Cornus mas, Satureja khuzestanica, Withania somnifera, Fumaria parviflora, zingiber officinale, cinnamomum zeylanicum and Phoenix dactylifera are used in the male reproductive system.
CONCLUSIONS
Plants can probably be useful in increasing fertility due to their antioxidant power and low side effects.
Topics: Humans; Infertility; Male; Plants, Medicinal; Seeds; Spermatozoa; Testosterone
PubMed: 35234023
DOI: 10.5935/1518-0557.20210108 -
European Urology Oncology Jun 2023Androgen receptor signaling inhibitor (ARSi) agents are emerging as standard treatments for prostate cancer across the disease spectrum, but much remains unknown... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Androgen receptor signaling inhibitor (ARSi) agents are emerging as standard treatments for prostate cancer across the disease spectrum, but much remains unknown regarding how their side-effect profiles compare.
OBJECTIVE
To systematically evaluate the literature regarding adverse events (AEs) between the ARSi drugs abiraterone, apalutamide, darolutamide, and enzalutamide in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic CRPC (nmCRPC), and metastatic castration-sensitive prostate cancer (mCSPC).
EVIDENCE ACQUISITION
PubMed, Web of Science, and Embase were queried for double-blind, randomized controlled trials (RCTs) of ARSi therapy up to September 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Two teams reviewed titles and abstracts, and 14 RCTs were included for analysis.
EVIDENCE SYNTHESIS
Forest plots were used to summarize risk ratios for the most common AEs. According to surface under the cumulative ranking curve (SUCRA) values, enzalutamide was ranked as the most toxic treatment regarding hypertension outcomes (SUCRA 0%, most likely to be the bottom-ranked treatment) in both mCRPC and nmCRPC (SUCRA 0%). Enzalutamide was also ranked as the most toxic regarding headache across all prostate cancer entities (SUCRA 0%, for mCRPC, 1% for nmCRPC, and 3% for mCSPC).
CONCLUSIONS
Our findings suggest that the ARSi side-effect profiles do not significantly differ, except that enzalutamide was ranked the most toxic regarding hypertension in mCRPC and nmCRPC, and the most toxic regarding headache across all prostate cancer settings. These results highlight the importance of close blood-pressure monitoring for enzalutamide, and future research should explore possible connections between cardiovascular and neurological risk with ARSi therapy. In addition, these comparisons rely on the validity of cross-trial comparisons.
PATIENT SUMMARY
We reviewed the side-effect profiles of second-generation antiandrogen drugs for the treatment of prostate cancer. Side effects were similar, apart from higher risk of high blood pressure and headache risk with enzalutamide.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Network Meta-Analysis; Androgen Receptor Antagonists; Headache; Randomized Controlled Trials as Topic
PubMed: 36682938
DOI: 10.1016/j.euo.2023.01.001 -
Frontiers in Pediatrics 2022Pubertal gynecomastia (PG), a benign condition with varied reported prevalence, typically appears at 13-14 years-old and is mostly idiopathic and self-limited.... (Review)
Review
BACKGROUND
Pubertal gynecomastia (PG), a benign condition with varied reported prevalence, typically appears at 13-14 years-old and is mostly idiopathic and self-limited. Psychologic impairments are common among adolescents with gynecomastia. Surgical intervention is reserved to severe cases and is offered towards the end of puberty. Pharmacological treatment is seldom given by clinicians mainly due to insufficient published data. We conducted this systematic literature review to assess the efficacy, safety, side effects, and complications of pharmacological treatments published.
METHODS
MEDLINE, Embase, and Cochrane CENTRAL were searched for the terms "gynecomastia", "pubertal", and "adolescent" in conjunction with medications from the Selective Estrogen Receptor Modulator (SERM), aromatase inhibitors (AI), and androgens groups in different combinations to optimize the search results. Exclusion criteria included: studies based on expert opinion, similar evidence-based medicine levels studies, and studies which discuss gynecomastia in adults. Selected articles were assessed by two authors. Data collected included: the level of evidence, population size, treatment regimen, follow-up, outcomes, complications, and side effects.
RESULTS
Of 1,425 published studies found and examined meticulously by the authors, only 24 publications met all the study research goals. These were divided into 16 publications of patients treated with SERM, of whom four had AI and four androgens. In general, the data regarding pharmacologic therapy for PG is partial, with insufficient evidence-based research. Tamoxifen and SERM drugs have long been used as treatments for PG. Tamoxifen was the chosen drug of treatment in most of the reviewed studies and found to be effective, safe, and with minimal side effects.
CONCLUSIONS
Pharmacological treatment as a new standard of care has an advantage in relieving behavioral and psychological distress. Although high quality publications are lacking, pharmacological intervention with tamoxifen is appropriate in select patients. Conduction large-scale high-quality studies are warranted with various drugs.
PubMed: 36389365
DOI: 10.3389/fped.2022.978311 -
Life (Basel, Switzerland) Jan 2023Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of the female reproductive system, including polycystic ovary syndrome (PCOS). The aim of... (Review)
Review
Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of the female reproductive system, including polycystic ovary syndrome (PCOS). The aim of this review was to summarize the knowledge about the association of EDCs (bisphenols, parabens, and triclosan) with PCOS. We conducted an electronic literature search using PubMed for studies published between January 2007 and October 2022 on EDCs related to PCOS, and evaluated the association of PCOS with bisphenols, parabens and triclosan in 15 articles. Most studies revealed significantly higher plasma, urinary or follicular fluid levels of bisphenol A (BPA) in women with PCOS, and some showed a positive correlation of BPA with insulin resistance, polycystic morphology on ultrasound, hepatic steatosis, bilirubin levels, as well as free androgen index, androstenedione and testosterone serum levels, and markers of low-grade chronic inflammation. There was a negative correlation of BPA with markers of ovarian reserve, sex hormone binding globulin and vitamin D-binding protein. Parabens and triclosan have been studied in only one study each, with no significant associations with PCOS observed. Our review revealed an association of BPA with PCOS and negative effects of BPA on human ovaries; more research is needed to assess the potential associations of parabens and triclosan with PCOS.
PubMed: 36676087
DOI: 10.3390/life13010138