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Dermatology (Basel, Switzerland) 2021Over-the-counter antiaging formulations aim to prevent or minimize the signs of aging skin, and to maintain the benefits obtained from different cosmetic procedures....
Over-the-counter antiaging formulations aim to prevent or minimize the signs of aging skin, and to maintain the benefits obtained from different cosmetic procedures. Even though a huge selection of such products is available on the market, evidence and good clinical practice of the data supporting their use are oftentimes lacking. In this systematic review, the authors reviewed scientific data available in the published literature on the most common ingredients used in antiaging cosmetics, with a particular focus on in vivo studies.
Topics: Administration, Cutaneous; Antioxidants; Humans; Hyaluronic Acid; Nonprescription Drugs; Peptides; Phenols; Phytochemicals; Retinoids; Skin Aging; Ubiquinone
PubMed: 32882685
DOI: 10.1159/000509296 -
JAMA Jan 2019The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk.
OBJECTIVE
To assess the association of aspirin use for primary prevention with cardiovascular events and bleeding.
DATA SOURCES
PubMed and Embase were searched on Cochrane Library Central Register of Controlled Trials from the earliest available date through November 1, 2018.
STUDY SELECTION
Randomized clinical trials enrolling at least 1000 participants with no known cardiovascular disease and a follow-up of at least 12 months were included. Included studies compared aspirin use with no aspirin (placebo or no treatment).
DATA EXTRACTION AND SYNTHESIS
Data were screened and extracted independently by both investigators. Bayesian and frequentist meta-analyses were performed.
MAIN OUTCOMES AND MEASURES
The primary cardiovascular outcome was a composite of cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. The primary bleeding outcome was any major bleeding (defined by the individual studies).
RESULTS
A total of 13 trials randomizing 164 225 participants with 1 050 511 participant-years of follow-up were included. The median age of trial participants was 62 years (range, 53-74), 77 501 (47%) were men, 30 361 (19%) had diabetes, and the median baseline risk of the primary cardiovascular outcome was 9.2% (range, 2.6%-15.9%). Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).
CONCLUSIONS AND RELEVANCE
The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.
Topics: Aspirin; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Primary Prevention; Risk
PubMed: 30667501
DOI: 10.1001/jama.2018.20578 -
Environmental Health Perspectives Jul 2015Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer... (Review)
Review
BACKGROUND
Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled "BPA-free." Some of the chemical replacements, however, are also bisphenols and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes.
OBJECTIVES
This review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA.
METHODS
We conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol.
RESULTS
We identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive end points, and enzyme expression.
CONCLUSIONS
Based on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects.
CITATION
Rochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes.
Topics: Animals; Benzhydryl Compounds; Endocrine Disruptors; Humans; Phenols; Sulfones
PubMed: 25775505
DOI: 10.1289/ehp.1408989 -
Journal of Cosmetic Dermatology Dec 2022Bakuchiol (BAK), a meroterpene phenol abundant in the plant Psoralea corylifolia, is an emerging cosmeceutical agent with promising anti-aging, anti-inflammatory, and... (Review)
Review
BACKGROUND
Bakuchiol (BAK), a meroterpene phenol abundant in the plant Psoralea corylifolia, is an emerging cosmeceutical agent with promising anti-aging, anti-inflammatory, and antibacterial properties. The trend for "clean" skincare products and search for anti-aging retinoid alternatives have poised BAK as a "must-have" ingredient in skincare.
AIMS
Our aim was to review the data for the applications of BAK in dermatology.
METHODS
This is a systematic review of PubMed.
RESULTS
Thirty articles matched our search terms ["Bakuchiol" and "Dermatology"] or ["Bakuchiol" and "Skin"] of which one did not meet inclusion criteria, 16 were pre-clinical studies, seven clinical studies, three commentaries, two narrative reviews, and one report on adverse events. BAK has been mostly studied for its effects on photoaging, acne, and post-inflammatory hyperpigmentation (PIH), showing beneficial results comparable to those achieved by topical retinoids. While having no structural resemblance to retinoids, BAK can function as a retinol analog, through retinol-like regulation of gene expression. In in vivo studies, BAK was used alone or in combination with other products resulting in a significant reduction in photodamage, hyperpigmentation, wrinkle scores, and acne severity. Additionally, in vitro studies hinted at its anti-cancer properties by inhibiting epidermal growth factor induced neoplastic cell transformation. Also, demonstrated potential applications in psoriasis by normalizing keratinocyte activity and in pigmentary disorders through inhibition of melanogenesis. There was one adverse event case reported of contact dermatitis in the literature.
CONCLUSIONS
Bakuchiol is a retinol alternative with anti-aging, antibacterial, and anti-inflammatory properties. Additional studies are warranted to better understand its applications in dermatology.
Topics: Humans; Vitamin A; Retinoids; Phenols; Acne Vulgaris; Anti-Bacterial Agents
PubMed: 36176207
DOI: 10.1111/jocd.15420 -
Journal of Critical Care Aug 2021Compare outcomes of adult patients admitted to ICU- length of ICU stay, length of mechanical ventilation (MV), and time until extubation- according to the use of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Compare outcomes of adult patients admitted to ICU- length of ICU stay, length of mechanical ventilation (MV), and time until extubation- according to the use of propofol versus midazolam.
METHODS
We searched MEDLINE, EMBASE, LILACS, and Cochrane databases to retrieve RCTs that compared propofol and midazolam used as sedatives in adult ICU patients. We applied a random-effects, meta-analytic model in all calculations. We applied the Cochrane collaboration tool and GRADE. We separated patients into two groups: acute surgical patients (hospitalization up to 24 h) and critically-ill patients (hospitalization over 24 h and whose articles mostly mix surgical, medical and trauma patients).
RESULTS
Globally, propofol was associated with a reduced MV time of 4.46 h (MD: -4.46 [95% CI -7.51 to -1.42] p = 0.004, I2 = 63%, 6 studies) and extubation time of 7.95 h (MD: -7.95 [95% CI -9.86 to -6.03] p < 0.00001, I2 = 98%, 16 studies). Acute surgical patients sedation with propofol compared to midazolam was associated with a reduced ICU stay of 5.07 h (MD: -5.07 [95% CI -8.68 to -1.45] p = 0.006, I2 = 41%, 5 studies), MV time of 4.28 h (MD: -4.28; [95% CI -4.62 to -3.94] p < 0.0001, I2 = 0%, 3 studies), extubation time of 1.92 h (MD: -1.92; [95% CI -2.71 to -1.13] p = 0.00001, I2 = 89%, 9 studies). In critically-ill patients sedation with propofol compared to midazolam was associated with a reduced extubation time of 32.68 h (MD: -32.68 [95% CI -48.37 to -16.98] p = 0.0001, I2 = 97%, 9 studies). GRADE was very low for all outcomes.
CONCLUSIONS
Sedation with propofol compared to midazolam is associated with improved clinical outcomes in ICU, with reduced ICU stay MV time and extubation time in acute surgical patients and reduced extubation time in critically-ill patients.
Topics: Adult; Critical Care; Humans; Hypnotics and Sedatives; Intensive Care Units; Midazolam; Propofol; Respiration, Artificial
PubMed: 33838522
DOI: 10.1016/j.jcrc.2021.04.001 -
Phytotherapy Research : PTR Jun 2022Endometriosis, a gynecological disease that affects reproductive age women is difficultly controlled in the long term by currently available treatments, prompting... (Review)
Review
Endometriosis, a gynecological disease that affects reproductive age women is difficultly controlled in the long term by currently available treatments, prompting patients to adopt self-controlled interventions including dietary changes. The aim of this review is to provide evidence of how curcumin, quercetin, and resveratrol can act as natural interventions to control endometriosis. The review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was carried out in PubMed, Scopus, and Web of Science to gather together all the articles that study the specific actions of curcumin, resveratrol, or quercetin in endometriosis pathophysiology. All types of study designs including experimental data were considered. Thirty articles, including a clinical trial, were included. For the assessment of the quality of the selected studies that globally have "good quality", the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and the SYRCLE ROB tool criteria were used. By acting on mechanisms of inflammation, oxidative stress, cell proliferation, invasion and adhesion, apoptosis, angiogenesis and glucose and lipid metabolism, curcumin, quercetin, and resveratrol showed to have beneficial effects, evidencing their potential application in the endometriosis treatment. However, future clinical studies are necessary to determine the real efficacy of these compounds in human endometriosis.
Topics: Antioxidants; Curcumin; Endometriosis; Female; Humans; Quercetin; Resveratrol
PubMed: 35583746
DOI: 10.1002/ptr.7464 -
Critical Reviews in Food Science and... 2021Curcumin is the main phenolic compound in turmeric. It has been investigated recently due to its numerous medicinal properties and health benefits. However, few studies...
Curcumin is the main phenolic compound in turmeric. It has been investigated recently due to its numerous medicinal properties and health benefits. However, few studies assessed the effects of curcumin supplementation on physical activity practice. Therefore, the purpose of this review is to assess the available evidences with human beings about the potential effects of curcumin supplementation on sport and physical exercise. This systematic review was conducted within the period from January to February, 2019, following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. The LILACS, Medline, SciELO and PubMed databases were used for the search, with no publication date limit. The following terms, with the respective Boolean operators, were searched: "curcumin" AND sports; "curcumin" AND exercise; curcumin AND "aerobic exercise"; "curcumin" AND "resistance exercise"; "curcumin" AND "endurance exercise"; "curcumin" AND "strength exercise". Eleven papers were selected for this review. Most of the studies displayed positive effects of the curcumin supplementation for athletes and physical exercise practitioners, and no side effects were reported. Participants supplemented with curcumin displayed reduced inflammation and oxidative stress, decreased pain and muscle damage, superior recovery and muscle performance, better psychological and physiological responses (thermal and cardiovascular) during training and improved gastrointestinal function. Curcumin supplementation appears to be safe and beneficial for sport and physical exercise in human beings. PROSPERO (CRD42019126763).
Topics: Curcumin; Dietary Supplements; Exercise; Humans; Sports
PubMed: 32282223
DOI: 10.1080/10408398.2020.1749025 -
The Cochrane Database of Systematic... Jul 2017Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their... (Review)
Review
BACKGROUND
Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol.
OBJECTIVES
To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use.
METHODS
We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events.
MAIN RESULTS
We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes.Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both.Reviews on buprenorphine, codeine with or without paracetamol, hydromorphone, methadone, tramadol with or without paracetamol, tapentadol, and oxycodone did not have information about the primary outcome of mild or no pain at 14 days, although that on oxycodone indicated that average pain scores were within that range. Two reviews, on oral morphine and transdermal fentanyl, reported that 96% of 850 participants achieved that goal.Adverse event withdrawal was reported by five reviews, at rates of between 6% and 19%. Participants with at least one adverse event were reported by three reviews, at rates of between 11% and 77%.Our GRADE assessment of evidence quality was very low for all outcomes, because many studies in the reviews were at high risk of bias from several sources, including small study size.
AUTHORS' CONCLUSIONS
The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.
Topics: Acetaminophen; Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Cancer Pain; Codeine; Fentanyl; Humans; Hydromorphone; Methadone; Oxycodone; Phenols; Review Literature as Topic; Tapentadol; Tramadol
PubMed: 28683172
DOI: 10.1002/14651858.CD012592.pub2 -
The Cochrane Database of Systematic... Jul 2016Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in these patients.
OBJECTIVES
To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease.
SEARCH METHODS
We searched PubMed, EMBASE, MEDLINE and the Cochrane Central Library from inception to June 2015 to identify relevant studies. There were no language restrictions. We also searched reference lists from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2015) of the American Gastroenterological Association and American College of Gastroenterology.
SELECTION CRITERIA
Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included.
DATA COLLECTION AND ANALYSIS
Data extraction and assessment of methodological quality was independently performed by the investigators and any disagreement was resolved by discussion and consensus. We assessed methodological quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Secondary outcomes included mean Crohn's disease activity index (CDAI) scores, adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes we calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (CI) using a random-effects model. For continuous outcomes we calculated the mean difference (MD) and 95% CI using a random-effects model. Sensitivity analyses based on a fixed-effect model and duration of therapy were conducted where appropriate.
MAIN RESULTS
Twenty studies (2367 patients) were included. Two studies were judged to be at high risk of bias due to lack of blinding. Eight studies were judged to be at high risk of bias due to incomplete outcomes data (high drop-out rates) and potential selective reporting. The other 10 studies were judged to be at low risk of bias. A non-significant trend in favour of sulfasalazine over placebo for inducing remission was observed, with benefit confined mainly to patients with Crohn's colitis. Forty-five per cent (63/141) of sulfasalazine patients entered remission at 17-18 weeks compared to 29% (43/148) of placebo patients (RR 1.38, 95% CI 1.00 to 1.89, 2 studies). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (106 events). There was no difference between sulfasalazine and placebo in adverse event outcomes. Sulfasalazine was significantly less effective than corticosteroids and inferior to combination therapy with corticosteroids (RR 0.64, 95% CI 0.47 to 0.86, 1 study, 110 patients). Forty-three per cent (55/128) of sulfasalazine patients entered remission at 17 to 18 weeks compared to 60% (79/132) of corticosteroid patients (RR 0.68, 95% CI 0.51 to 0.91; 2 studies, 260 patients). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (134 events). Sulfasalazine patients experienced significantly fewer adverse events than corticosteroid patients (RR 0.43, 95% CI 0.22 to 0.82; 1 study, 159 patients). There was no difference between sulfasalazine and corticosteroids in serious adverse events or withdrawal due to adverse events. Olsalazine was less effective than placebo in a single trial (RR 0.36, 95% CI 0.18 to 0.71; 91 patients). Low dose mesalamine (1 to 2 g/day) was not superior to placebo for induction of remission. Twenty-three per cent (43/185) of low dose mesalamine patients entered remission at week 6 compared to 15% (18/117) of placebo patients (RR = 1.46, 95% CI 0.89 to 2.40; n = 302). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to risk of bias (incomplete outcome data) and sparse data (61 events). There was no difference between low dose mesalamine and placebo in the proportion of patients who had adverse events (RR 1.33, 95% CI 0.91 to 1.96; 3 studies, 342 patients) or withdrew due to adverse events (RR 1.21, 95% CI 0.75 to 1.95; 3 studies, 342 patients). High dose controlled-release mesalamine (4 g/day) was not superior to placebo, inducing a clinically non significant reduction in CDAI (MD -19.8 points, 95% CI -46.2 to 6.7; 3 studies, 615 patients), and was also inferior to budesonide (RR 0.56, 95% CI 0.40 to 0.78; 1 study, 182 patients, GRADE = low). While high dose delayed-release mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02, 95% CI 0.75 to 5.45; 1 study, 38 patients, GRADE = very low), no significant difference in efficacy was found when compared to conventional corticosteroids (RR 1.04, 95% CI 0.79 to 1.36; 3 studies, 178 patients, GRADE = moderate) or budesonide (RR 0.89, 95% CI 0.76 to 1.05; 1 study, 307 patients, GRADE = moderate). However, these trials were limited by risk of bias (incomplete outcome data) and sparse data (small numbers of events). There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. Adverse events that were commonly reported included headache, nausea, vomiting, abdominal pain and diarrhea.
AUTHORS' CONCLUSIONS
Sulfasalazine is only modestly effective with a trend towards benefit over placebo and is inferior to corticosteroids for the treatment of mildly to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3.2 to 4 g/day) is not more effective than placebo for inducing response or remission. However, trials assessing the efficacy of high dose mesalamine (4 to 4.5 g/day) compared to budesonide yielded conflicting results and firm conclusions cannot be made. Future large randomized controlled trials are needed to provide definitive evidence on the efficacy of aminosalicylates in active Crohn's disease.
Topics: Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Delayed-Action Preparations; Gastrointestinal Agents; Humans; Induction Chemotherapy; Mesalamine; Randomized Controlled Trials as Topic; Sulfasalazine
PubMed: 27372735
DOI: 10.1002/14651858.CD008870.pub2 -
Menopause (New York, N.Y.) Jan 2024The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared... (Meta-Analysis)
Meta-Analysis
Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause.
IMPORTANCE
The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared with placebo in two phase 3 randomized controlled trials. Its efficacy relative to available therapies is unknown.
OBJECTIVE
We conducted a systematic review and Bayesian network meta-analysis to compare efficacy with fezolinetant 45 mg and hormone therapy (HT) and non-HT for VMS in postmenopausal women.
EVIDENCE REVIEW
Using OvidSP, we systematically searched multiple databases for phase 3 or 4 randomized controlled trials in postmenopausal women with ≥7 moderate to severe VMS per day or ≥50 VMS per week published/presented in English through June 25, 2021. Mean change in frequency and severity of moderate to severe VMS from baseline to week 12 and proportion of women with ≥75% reduction in VMS frequency at week 12 were assessed using fixed-effect models.
FINDINGS
The network meta-analysis included data from the pooled phase 3 fezolinetant trials plus 23 comparator publications across the outcomes analyzed (frequency, 19 [34 regimens]; severity, 6 [7 regimens]; ≥75% response, 9 [15 regimens]). Changes in VMS frequency did not differ significantly between fezolinetant 45 mg and any of the 27 HT regimens studied. Fezolinetant 45 mg reduced the frequency of moderate to severe VMS events per day significantly more than all non-HTs evaluated: paroxetine 7.5 mg (mean difference [95% credible interval {CrI}], 1.66 [0.63-2.71]), desvenlafaxine 50 to 200 mg (mean differences [95% CrI], 1.12 [0.10-2.13] to 2.16 [0.90-3.40]), and gabapentin ER 1800 mg (mean difference [95% CrI], 1.63 [0.48-2.81]), and significantly more than placebo (mean difference, 2.78 [95% CrI], 1.93-3.62]). Tibolone 2.5 mg (the only HT regimen evaluable for severity) significantly reduced VMS severity compared with fezolinetant 45 mg. Fezolinetant 45 mg significantly reduced VMS severity compared with desvenlafaxine 50 mg and placebo and did not differ significantly from higher desvenlafaxine doses or gabapentin ER 1800 mg. For ≥75% responder rates, fezolinetant 45 mg was less effective than tibolone 2.5 mg (not available in the United States) and conjugated estrogens 0.625 mg/bazedoxifene 20 mg (available only as 0.45 mg/20 mg in the United States), did not differ significantly from other non-HT regimens studied and was superior to desvenlafaxine 50 mg and placebo.
CONCLUSIONS
The only HT regimens that showed significantly greater efficacy than fezolinetant 45 mg on any of the outcomes analyzed are not available in the United States. Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS.
RELEVANCE
These findings may inform decision making with regard to the individualized management of bothersome VMS due to menopause.
Topics: Female; Humans; Hot Flashes; Desvenlafaxine Succinate; Network Meta-Analysis; Gabapentin; Bayes Theorem; Menopause; Estrogens, Conjugated (USP)
PubMed: 38016166
DOI: 10.1097/GME.0000000000002281