-
JAMA Network Open Nov 2022Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.
OBJECTIVE
To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs).
DATA SOURCES
This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022.
STUDY SELECTION
Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).
DATA EXTRACTION AND SYNTHESIS
Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
MAIN OUTCOMES AND MEASURES
Overall mortality and prostate cancer-specific mortality (PCSM).
RESULTS
Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes.
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.
Topics: Male; Humans; Prostatic Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Androgens; Androgen Antagonists; Hormone Replacement Therapy
PubMed: 36449294
DOI: 10.1001/jamanetworkopen.2022.42676 -
Physical Therapy Mar 2022Men with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) experience the loss of bone mineral density (BMD) and lean body mass, which can increase...
OBJECTIVE
Men with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) experience the loss of bone mineral density (BMD) and lean body mass, which can increase their risk of falls and fractures. Physical exercise programs with appropriate components and dosage are suggested to preserve BMD and muscle strength, thereby potentially reducing accidental falls and fractures and associated morbidity and mortality. These benefits can be obtained if exercise programs are feasible and safe and if patient adherence is adequate. This systematic review investigates the feasibility and safety of exercise programs aimed at preventing the risk of accidental falls and fractures and BMD loss in men with PCa undergoing ADT.
METHODS
MEDLINE, Embase, CINAHL, and the Cochrane Library were searched from database inception to June 7, 2021. Randomized controlled trials were included when they analyzed the feasibility and safety of experimental exercise programs targeting bone health in men with PCa receiving ADT. Two reviewers independently selected the studies, assessed their methodological quality, and extracted the data. Exercise feasibility was measured through recruitment, retention, and adherence rates. Exercise safety was measured through the number, type, and severity of adverse events. Furthermore, the components, setting, intensity, frequency, and duration of exercise programs were extracted.
RESULTS
Ten studies were included, with a total of 633 participants. Exercise consisted of a combination of aerobic, resistance, and impact-loading exercise or football training. Exercise is feasible in men with PCa undergoing ADT, although football training should be prescribed with caution for safety reasons.
CONCLUSION
Multicomponent exercise programs targeting bone health seem feasible and safe in this population; however, adverse events should be systematically documented according to current guidelines.
IMPACT
The study shows that men with PCa receiving ADT can safely perform exercise programs to preserve bone health and supports that those programs should become part of lifestyle habits.
LAY SUMMARY
Men with PCa who are receiving ADT can safely perform exercise programs to preserve bone health and should make exercise an important part of their lifestyle.
Topics: Androgen Antagonists; Androgens; Bone Density; Exercise; Exercise Therapy; Feasibility Studies; Humans; Male; Prostatic Neoplasms
PubMed: 34972863
DOI: 10.1093/ptj/pzab288 -
World Journal of Urology Apr 2022Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection... (Meta-Analysis)
Meta-Analysis
PURPOSE
Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT).
METHODS
We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I statistic, respectively.
RESULTS
Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68).
CONCLUSION
We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.
Topics: Androgen Antagonists; Androgens; COVID-19; Humans; Male; Pandemics; Prostatic Neoplasms; Retrospective Studies; Risk Factors; SARS-CoV-2; Severity of Illness Index
PubMed: 34477955
DOI: 10.1007/s00345-021-03810-6 -
Current Oncology (Toronto, Ont.) May 2022Health economic evaluations are needed to assess the impact on the healthcare system of emerging treatment patterns for advanced prostate cancer. The objective of this... (Review)
Review
The Health Economics of Metastatic Hormone-Sensitive and Non-Metastatic Castration-Resistant Prostate Cancer-A Systematic Literature Review with Application to the Canadian Context.
Health economic evaluations are needed to assess the impact on the healthcare system of emerging treatment patterns for advanced prostate cancer. The objective of this study is to review the scientific literature identifying cost-effectiveness and cost analyses that are assessing treatments for metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). : On 29 June 2021, we searched the scientific (MEDLINE, Embase, and EBSCO) and grey literature for health economic studies targeting mHSPC and nmCRPC. We used the CHEC-extended checklist and the Welte checklist for risk-of-bias assessment and transferability analysis, respectively. : We retained 20 cost-effectiveness and 4 cost analyses in the mHSPC setting, and 14 cost-effectiveness and 6 cost analyses in the nmCRPC setting. Docetaxel in combination with androgen deprivation therapy (ADT) was the most cost-effective treatment in the mHSPC setting. Apalutamide, darolutamide, and enzalutamide presented similar results vs. ADT alone and were identified as cost-effective treatments for nmCRPC. An increase in costs as patients transitioned from nmCRPC to mCRPC was noted. : We concluded that there is an important unmet need for health economic evaluations in the mHSPC and nmCRPC setting incorporating real-world data to support healthcare decision making.
Topics: Androgen Antagonists; Canada; Docetaxel; Hormones; Humans; Male; Prostatic Neoplasms, Castration-Resistant
PubMed: 35621665
DOI: 10.3390/curroncol29050275 -
Clinical & Experimental Metastasis Dec 2022Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or...
Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3-6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2-98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0-100%). PFS was reported as a crude rate in 11 studies (range 27.3-68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0-50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach.
Topics: Humans; Male; Androgen Antagonists; Prostatic Neoplasms; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 35980556
DOI: 10.1007/s10585-022-10183-6 -
World Journal of Diabetes Mar 2020Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of...
BACKGROUND
Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of adverse cardiovascular outcomes, including myocardial infarction and stroke. This may be related to the effects of testosterone or estradiol therapy on body composition, fat distribution, and insulin resistance but the effect of gender-affirming hormone therapy on these cardiovascular risk factors has not been extensively examined.
AIM
To evaluate the impact of gender-affirming hormone therapy on body composition and insulin resistance in transgender individuals, to guide clinicians in minimising cardiovascular risk.
METHODS
We performed a review of the literature based on PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining body composition, insulin resistance or body fat distribution in transgender individuals aged over 18 years on established gender-affirming hormone therapy. Studies were selected for full-text analysis if they investigated transgender individuals on any type of gender-affirming hormone therapy and reported effects on lean mass, fat mass or insulin resistance.
RESULTS
The search strategy identified 221 studies. After exclusion of studies that did not meet inclusion criteria, 26 were included (2 cross-sectional, 21 prospective-uncontrolled and 3 prospective-controlled). Evidence in transgender men suggests that testosterone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Evidence in transgender women suggests that feminising hormone therapy (estradiol, with or without anti-androgen agents) decreases lean mass, increases fat mass, and may worsen insulin resistance. Changes to body composition were consistent across almost all studies: Transgender men on testosterone gained lean mass and lost fat mass, and transgender women on oestrogen experienced the reverse. No study directly contradicted these trends, though several small studies of short duration reported no changes. Results for insulin resistance are less consistent and uncertain. There is a paucity of prospective controlled research, and existing prospective evidence is limited by small sample sizes, short follow up periods, and young cohorts of participants.
CONCLUSION
Further research is required to further characterise the impact of gender-affirming hormone therapy on body composition and insulin resistance in the medium-long term. Until further evidence is available, clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.
PubMed: 32180895
DOI: 10.4239/wjd.v11.i3.66 -
Cureus Apr 2024Acne vulgaris, commonly called acne, is a skin condition affecting many individuals globally. It is a chronic condition characterized by developing pimples, blackheads... (Review)
Review
Acne vulgaris, commonly called acne, is a skin condition affecting many individuals globally. It is a chronic condition characterized by developing pimples, blackheads (open comedones), whiteheads (closed comedones), and other skin lesions. Acne usually appears on the face, neck, chest, and back. It is commonly associated with puberty and adolescence but can also affect adults of all ages. Acne can be very frustrating and embarrassing, leading to low self-esteem and social isolation. The condition arises from various factors, including clogged pores, excessive sebum production, bacteria, and inflammation. This systematic review assesses the effectiveness of topical antibiotics, retinoids, niacinamide, azelaic acid, and clascoterone in treating mild-to-moderate acne vulgaris. A comprehensive search across PubMed, PubMed Central, and Google Scholar yielded 10 articles focused on topical antibiotics, with findings from 198 subjects indicating the efficacy of doxycycline against inflammatory lesions. Retinoids, such as tretinoin and adapalene, significantly improved both lesion types (open and closed comedones). Niacinamide, examined in a randomized controlled trial involving 41 participants, reduced sebum production. Another study with 60 patients revealed that azelaic acid effectively reduced both inflammatory and non-inflammatory lesions. Clascoterone emerged as a promising antiandrogenic treatment, supported by a randomized controlled trial involving 4,440 patients. It is essential that individualized therapy, incorporating patient preferences and considering adverse effects, is emphasized for optimizing acne management.
PubMed: 38725769
DOI: 10.7759/cureus.57909 -
Asian Journal of Andrology 2020The first-line treatment options for high-risk prostate cancer (PCa) are definitive external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT)... (Comparative Study)
Comparative Study Meta-Analysis
The first-line treatment options for high-risk prostate cancer (PCa) are definitive external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT) and radical prostatectomy (RP) with or without adjuvant therapies. However, few randomized trials have compared the survival outcomes of these two treatments. To systematically evaluate the survival outcomes of high-risk PCa patients treated with EBRT- or RP-based therapy, a comprehensive and up-to-date meta-analysis was performed. A systematic online search was conducted for randomized or observational studies that investigated biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), and/or overall survival (OS), in relation to the use of RP or EBRT in patients with high-risk PCa. The summary hazard ratios (HRs) were estimated under the random effects models. We identified heterogeneity between studies using Q tests and measured it using I statistics. We evaluated publication bias using funnel plots and Egger's regression asymmetry tests. Seventeen studies (including one randomized controlled trial [RCT]) of low risk of bias were selected and up to 9504 patients were pooled. When comparing EBRT-based treatment with RP-based treatment, the pooled HRs for bRFS, CSS, and OS were 0.40 (95% confidence interval [CI]: 0.24-0.67), 1.36 (95% CI: 0.94-1.97), and 1.39 (95% CI: 1.18-1.62), respectively. Better OS for RP-based treatment and better bRFS for EBRT-based treatment have been identified, and there was no significant difference in CSS between the two treatments. RP-based treatment is recommended for high-risk PCa patients who value long-term survival, and EBRT-based treatment might be a promising alternative for elderly patients.
Topics: Androgen Antagonists; Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Male; Neoplasm Grading; Proportional Hazards Models; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy; Radiotherapy, Adjuvant; Risk; Survival Rate
PubMed: 31603140
DOI: 10.4103/aja.aja_111_19 -
Andrology May 2020Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer. Whether androgen deprivation therapy (ADT) is associated with an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer. Whether androgen deprivation therapy (ADT) is associated with an increased risk of developing cardiovascular-related disease is poorly defined.
OBJECTIVES
The aim of the present meta-analysis is to explore the relationship between ADT and the risk of cardiac events. MATERIALS AND METHODS: For this systematic review and meta-analysis, we searched databases from inception to April 2019 for randomized controlled trials (RCT) or observational studies that reported data on ADT administration and cardiac event incidence. The connection was evaluated through estimating relative risk ratio (RR) and 95% confidence intervals (CIs).
RESULTS
A significantly increased acute myocardial infarction (AMI) was detected in the ADT group compared with the control group (RR = 1.19, 95% confidence interval (CI), 1.02-1.39, P < .05). A significant difference between cardiovascular disease (CVD) and ADT was also observed, with summary RR = 1.25, 95% CI, 1.11-1.40, P < .05. Furthermore, our study also suggested ADT was not related to increased incidence of sudden cardiac death (SCD) (RR = 1.13, 95% CI, 0.92-1.38, P = .24); AMI and CVD were not connected with the duration of ADT (AMI: RR = 1.31; 95% CI, 0.66-2.63, P = .44, for > 5 year group; CVD: RR = 1.12, 95% CI, 0.97-1.30, P = .12, for > 5 year group). In addition, the RR for risk of CVD was 1.28 (95% CI, 1.01-1.62, P < .05) for men with PCa on new hormonal agents.
DISCUSSION
Various ADT modalities have different impact on cardiovascular disease risk in different level. Long-term application of ADT is not associated with increased risk of AMI and CVD. Both abiraterone and enzalutamide could significantly increase the incidence of cardiac events in patients who suffered from prostate cancer. Cautions and periodic cardiovascular elevation are necessary for patients before the ADT starting.
CONCLUSIONS
Androgen deprivation therapy is associated with increased risk of AMI, CHD, in contrast, this association is not detected in SCD.
Topics: Androgen Antagonists; Cardiovascular Diseases; Humans; Male; Prostatic Neoplasms
PubMed: 31743594
DOI: 10.1111/andr.12731 -
The Cochrane Database of Systematic... Nov 2020Gender dysphoria is described as a mismatch between an individual's experienced or expressed gender and their assigned gender, based on primary or secondary sexual...
BACKGROUND
Gender dysphoria is described as a mismatch between an individual's experienced or expressed gender and their assigned gender, based on primary or secondary sexual characteristics. Gender dysphoria can be associated with clinically significant psychological distress and may result in a desire to change sexual characteristics. The process of adapting a person's sexual characteristics to their desired sex is called 'transition.' Current guidelines suggest hormonal and, if needed, surgical intervention to aid transition in transgender women, i.e. persons who aim to transition from male to female. In adults, hormone therapy aims to reverse the body's male attributes and to support the development of female attributes. It usually includes estradiol, antiandrogens, or a combination of both. Many individuals first receive hormone therapy alone, without surgical interventions. However, this is not always sufficient to change such attributes as facial bone structure, breasts, and genitalia, as desired. For these transgender women, surgery may then be used to support transition.
OBJECTIVES
We aimed to assess the efficacy and safety of hormone therapy with antiandrogens, estradiol, or both, compared to each other or placebo, in transgender women in transition.
SEARCH METHODS
We searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Biosis Preview, PsycINFO, and PSYNDEX. We carried out our final searches on 19 December 2019.
SELECTION CRITERIA
We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cohort studies that enrolled transgender women, age 16 years and over, in transition from male to female. Eligible studies investigated antiandrogen and estradiol hormone therapies alone or in combination, in comparison to another form of the active intervention, or placebo control.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane to establish study eligibility.
MAIN RESULTS
Our database searches identified 1057 references, and after removing duplicates we screened 787 of these. We checked 13 studies for eligibility at the full text screening stage. We excluded 12 studies and identified one as an ongoing study. We did not identify any completed studies that met our inclusion criteria. The single ongoing study is an RCT conducted in Thailand, comparing estradiol valerate plus cyproterone treatment with estradiol valerate plus spironolactone treatment. The primary outcome will be testosterone level at three month follow-up.
AUTHORS' CONCLUSIONS
We found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition. This lack of studies shows a gap between current clinical practice and clinical research. Robust RCTs and controlled cohort studies are needed to assess the benefits and harms of hormone therapy (used alone or in combination) for transgender women in transition. Studies should specifically focus on short-, medium-, and long-term adverse effects, quality of life, and participant satisfaction with the change in male to female body characteristics of antiandrogen and estradiol therapy alone, and in combination. They should also focus on the relative effects of these hormones when administered orally, transdermally, and intramuscularly. We will include non-controlled cohort studies in the next iteration of this review, as our review has shown that such studies provide the highest quality evidence currently available in the field. We will take into account methodological limitations when doing so.
Topics: Androgen Antagonists; Drug Therapy, Combination; Estradiol; Estrogens; Female; Humans; Male; Placebos; Sex Reassignment Procedures; Transgender Persons
PubMed: 33251587
DOI: 10.1002/14651858.CD013138.pub2