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BMC Gastroenterology Mar 2021There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review...
BACKGROUND/AIMS
There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review we aimed to address pharmacokinetics (PK), safety, and effects on cardiovascular (CV) outcomes of statins in cirrhosis.
METHODS
Our systematic search in several electronic databases and repositories of two regulatory bodies up to 2020-06-11 yielded 22 articles and 2 drug monographs with relevant data.
RESULTS
Rosuvastatin and pitavastatin showed minimal PK changes in Child-Pugh A cirrhosis. Only rosuvastatin was assessed in a repeated dosing PK study. Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials. There was insufficient data to assess CV effects of statins in cirrhosis. Clinical trials in cirrhosis were limited to simvastatin, atorvastatin, and pravastatin. In patients taking simvastatin 40 mg, pooled frequency of rhabdomyolysis was 2%, an incidence 40-fold higher than that reported in non-cirrhosis patients, while this was no rhabdomyolysis observed in patients on simvastatin 20 mg, atorvastatin 20 mg, or pravastatin 40 mg. Drug-induced liver injury was of difficult interpretation due to co-existence of muscle damage. No overt liver failure was reported.
CONCLUSIONS
Simvastatin 40 mg should be avoided in decompensated cirrhosis. Safety data on simvastatin 20 mg or other statins are based on small study sample size. This rarity of evidence combined with lack of data in dose adjustment methods in cirrhosis is a barrier for using statins for CV indications or for investigational use for liver indications.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Pravastatin; Simvastatin
PubMed: 33726685
DOI: 10.1186/s12876-021-01704-w -
European Journal of Preventive... Aug 2013The extent to which individual statins vary in terms of their impact on serum lipid levels has been studied mainly on the basis of placebo-controlled trials. Our... (Meta-Analysis)
Meta-Analysis Review
AIMS
The extent to which individual statins vary in terms of their impact on serum lipid levels has been studied mainly on the basis of placebo-controlled trials. Our objective was to review and quantify the dose-comparative effects of different statins on serum lipid levels using both placebo- and active-comparator trials.
METHODS
We systematically reviewed randomized trials evaluating different statins in participants with, or at risk of developing, cardiovascular disease. We performed random-effects Bayesian network meta-analyses to quantify the the relative potency of individual statins across all possible dose combinations using both direct and indirect evidence. Dose-comparative effects were determined by estimating the mean change from baseline in serum lipids as compared to control treatment. (systematic review registration: PROSPERO 2011:CRD42011001470).
RESULTS
We included 181 placebo-controlled and active-comparator trials including 256,827 individuals. There were 83 two-armed placebo-controlled trials and the remaining 98 were two- or multi-armed active-comparator trials. All statins reduced serum LDL and total cholesterol levels: higher doses resulted in higher reductions in pretreatment LDL and total cholesterol concentrations. In absolute terms, all statins significantly reduced LDL cholesterol levels as compared to control treatment from average baseline levels of approximately 150 mg/dl, except for fluvastatin at ≤20 mg/day and lovastatin at ≤10 mg/day. Atorvastatin, rosuvastatin, and simvastatin were broadly equivalent in terms of their LDL cholesterol-lowering effects. Dose-comparative effects of indivudual statins were not different between those with and without coronary heart disease at baseline. According to meta-regression analyses, LDL cholesterol-lowering effects of individual statins were not impacted by differences across trials in terms of baseline mean age and proportion of women as trial participants. Pretreatment LDL cholesterol concentrations had a marginally statistically significant effect on LDL cholesterol change from baseline. Mean differences from baseline in HDL cholesterol as compared to control treatment was not significant for any statin-dose combination.
CONCLUSIONS
The findings of this comprehensive review provide supporting evidence for the dose-response relationship of statins in reducing LDL and total cholesterol. The LDL cholesterol-reducing effects of some statins appear less pronounced than the findings of previous meta-analyses, which is particularly the case for the high-dose formulations of atorvastatin and rosuvastatin. The most consistent evidence for a combined reduction in both LDL and total cholesterol was achieved with atorvastatin at >40 mg/day, rosuvastatin at >10 mg/day, and simvastatin at >40 mg/day, which appear equivalent in terms of their LDL and total cholesterol-reducing effects.
Topics: Bayes Theorem; Biomarkers; Cardiovascular Diseases; Dose-Response Relationship, Drug; Dyslipidemias; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Markov Chains; Monte Carlo Method; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 23529608
DOI: 10.1177/2047487313483600 -
Cardiovascular Drugs and Therapy Apr 2014Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI).... (Review)
Review
PURPOSE
Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI). Although the coronary intervention is undoubtedly beneficial, reperfusion itself can induce processes resulting in additional myocardial damage-a phenomenon known as ischemia-reperfusion injury (IRI). Oxidative stress is one of the major factors contributing to IRI. This systematic review focuses on the effect of antioxidant therapy on reperfusion triggered oxidative stress and myocardial IRI in patients with STEMI.
METHODS
We performed a systematic search in EMBASE and Pubmed and included eight randomised clinical trials evaluating edaravone, allopurinol, vitamin c, nicorandil, N-acetylcysteine, glucose-insulin-potassium, atorvastatin and deferoxamine.
RESULTS
Administration of edaravone, allopurinol, atorvastatin and nicorandil as a supplement to primary PCI significantly reduced oxidative stress and myocardial damage as well as improved cardiac function and clinical outcomes. Treatment with deferoxamine and N-acetylcysteine reduced the oxidative stress but an effect on the clinical outcome parameters could not be shown.
CONCLUSIONS
Preliminary studies of edaravone, allopurinol, atorvastatin and nicorandil seems promising though larger clinical trials with a wider range of clinical outcome parameters and trials of higher methodological quality should confirm the clinical benefits before a general recommendation can be given. Moreover, the included studies revealed a complex link between oxidative stress and cardiac function and/or cardiac adverse events and in order to further elucidate the detrimental role of oxidative stress in IRI in relation to primary PCI the assessment of oxidative stress and the clinical outcome parameters should be standardized.
Topics: Antioxidants; Humans; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Oxidative Stress; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24532094
DOI: 10.1007/s10557-014-6511-3 -
Thrombosis and Haemostasis Aug 2015D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors,... (Meta-Analysis)
Meta-Analysis Review
D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors, but their effect on plasma D-dimer levels is controversial. Therefore, the aim of this meta-analysis was to evaluate the association between statin therapy and plasma D-dimer levels. We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to September 25, 2014) to identify randomised controlled trials (RCTs) investigating the impact of statin therapy on plasma D-dimer levels. Two independent reviewers extracted data on study characteristics, methods and outcomes. Meta-analysis of data from nine RCTs with 1,165 participants showed a significant effect of statin therapy in reducing plasma D-dimer levels (standardised mean difference [SMD]: -0.988 µg/ml, 95 % confidence interval [CI]: -1.590 - -0.385, p=0.001). The effect size was robust in sensitivity analysis and omission of no single study significantly changed the overall estimated effect size. In the subgroup analysis, the effect of statins on plasma D-dimer levels was significant only in the subsets of studies with treatment duration ≥ 12 weeks (SMD: -0.761 µg/ml, 95 %CI: -1.163- -0.360; p< 0.001), and for lipophilic statins (atorvastatin and simvastatin) (SMD: -1.364 µg/ml, 95 % CI: -2.202- -0.526; p=0.001). Hydrophilic statins (pravastatin and rosuvastatin) did not significantly reduce plasma D-dimer levels (SMD: -0.237 µg/ml, 95 %CI: -1.140-0.665, p=0.606). This meta-analysis of RCTs suggests a decrease of plasma D-dimer levels after three months of statin therapy, and especially after treatment with lipophilic statins. Well-designed trials are required to validate these results.
Topics: Anticoagulants; Biomarkers; Blood Coagulation; Dyslipidemias; Fibrin Fibrinogen Degradation Products; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 26017749
DOI: 10.1160/TH14-11-0937 -
Frontiers in Aging Neuroscience 2021Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness...
Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness of different classes of medication. We performed a Bayesian network meta-analysis to compare and rank the efficacy and safety of five drug regimens to determine the best treatment for this group of patients. We systematically searched PubMed, Medline, clinicaltrials.gov, the Cochrane database, and Embase to identify relevant randomized clinical trials (RCTs) comparing drug treatments in adult patients with CSDH. A network meta-analysis was conducted using a Bayesian framework. Random- and fixed-effects models were used to pool the network results, and the preferred model was selected by comparing the deviance information criteria (DIC). Efficacy outcomes included recurrence requiring surgery, changes in hematoma volume, and a good recovery. The safety outcomes were treatment-related adverse events and all-cause mortality. In this Bayesian network meta-analysis, available data were obtained from 12 eligible trials, including 2,098 patients and 5 techniques. Compared to placebo, atorvastatin (RR: 0.45, 95% CrI: 0.24-0.81) and dexamethasone (RR: 0.38, 95% CrI: 0.22-0.63) were similarly effective in reducing recurrence requiring surgery by 55% and 62%, respectively. Dexamethasone (RR: 0.46, 95% CrI: 0.23-0.91) was more effective in reducing recurrence requiring surgery than goreisan. Additionally, atorvastatin reduced the hematoma volume to a greater extent than placebo (MD: -7.44, 95% CrI: -9.49 to -5.43) or goreisan (MD: -14.09, 95% CrI: -23.35 to -4.82). Moreover, tranexamic acid (MD: -12.07, 95% CrI: -21.68 to -2.29) reduced the hematoma volume to a greater extent than goreisan. No significant differences were detected between drugs and placebo with regard to a good recovery. In terms of safety, dexamethasone (RR: 1.96, 95% CrI: 1.20-3.28) increased the risk of mortality compared to placebo. These findings suggest that dexamethasone is the best treatment to reduce recurrence and atorvastatin is the best treatment to reduce hematoma volume in patients with CSDH. However, clinicians should pay close attention to the elevated risk of all-cause mortality and potential adverse events caused by dexamethasone. Future well-designed RCTs with more participants are needed to verify these findings. http://osf.io/u9hqp.
PubMed: 34276343
DOI: 10.3389/fnagi.2021.684501 -
BMC Medicine Feb 2013Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.
METHODS
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.
RESULTS
Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).
CONCLUSIONS
Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.
Topics: Adult; Aged; Anticholesteremic Agents; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Testosterone
PubMed: 23448151
DOI: 10.1186/1741-7015-11-57 -
The Cochrane Database of Systematic... Aug 2010The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD ss-amyloid protein (Ass) is deposited... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD ss-amyloid protein (Ass) is deposited in the form of extracellular plaques and previous studies have determined Ass generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction it is biologically plausible they may be efficacious in the treatment of AD and dementia.
OBJECTIVES
To assess the clinical efficacy and tolerability of statins in the treatment of dementia.
SEARCH STRATEGY
We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (27 October 2008).
SELECTION CRITERIA
Double-blind, randomized controlled trials of statins given for at least six months in people with a diagnosis of dementia.
DATA COLLECTION AND ANALYSIS
Two independent authors extracted and assessed data independently against the inclusion criteria. Data were pooled where appropriate and entered into a meta-analysis.
MAIN RESULTS
Three studies were identified (748 participants, age range 50-90 years). All patients had a diagnosis of probable or possible AD according to standard criteria and most patients were established on a cholinesterase inhibitor. Treatment in ADCLT 2005 consisted of 80mg atorvastatin compared to placebo for 52 weeks, serum low density lipoprotein (LDL) cholesterol was reduced by 54% in the atorvastatin group. Treatment in Simons 2002 consisted of 40mg simvastatin compared to placebo for 26 weeks, serum LDL cholesterol was reduced by 52% in the simvastatin group. Treatment in LEADe 2010 consisted of 80mg atorvastatin compared to placebo for 72 weeks, LDL cholesterol was reduced by 50.2% by month 3 and remained constant through month 18. Change in Alzheimer's Disease Assessment Scale- cognitive subscale (ADAS-Cog) from baseline was a primary outcome in 3 studies; when data were pooled there was considerable heterogeneity so the random effects model was used, statins did not provide any beneficial effect in this cognitive measure [mean difference -1.12, 95% CI -3.99, 1.75, p = 0.44]. All studies provided change in Mini Mental State Examination (MMSE) from baseline; again random effects model was used due to considerable heterogeneity: there was no significant benefit from statins in this cognitive measure when the data were pooled [mean difference -1.53, 95% CI -3.28, 0.21, p = 0.08]. There was some evidence that patients on statins in ADCLT 2005 maintained better cognitive function if serum cholesterol was high at baseline, MMSE was higher at baseline or if they had an apolipoprotein E4 allele present. This would need to be confirmed in larger studies however. Treatment related adverse effects were available from two studies, LEADe 2010 and Simons 2002; when data were pooled there was no significant difference between statins and placebo [odds ratio 2.45, 95% CI 0.69, 8.62, p = 0.16]. There was no significant difference in global function, behaviour or activities of daily living in the statin and placebo groups. One large randomised controlled trial (RCT) ( CLASP 2008) has not yet published its results. There were no studies identified assessing role of statins in treatment of VaD. There was no evidence that statins were detrimental to cognition.
AUTHORS' CONCLUSIONS
There is insufficient evidence to recommend statins for the treatment of dementia. Analysis from the studies available, including one large RCT, indicate statins have no benefit on the outcome measures ADAS-Cog or MMSE. We need to await full results from CLASP 2008 before we can be certain. This Cochrane review will be updated as these results become available.
Topics: Alzheimer Disease; Atorvastatin; Dementia; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 20687089
DOI: 10.1002/14651858.CD007514.pub2 -
BMC Cardiovascular Disorders Dec 2015Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI). However, the results of those studies were inconsistent. To clarify the beneficial effects of atorvastatin added to the cell therapy with MSCs in animal model of acute myocardial infarction (AMI), we performed a systematic review and meta-analysis of case-control studies.
METHODS
Searches were performed using the PubMed database, the Excerpta Medica Database (Embase), the Science Citation Index, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search term included "Atorvastatin (or Ator)", "Mesenchymal Stem Cells (or Mesenchymal Stem Cell or MSC or MSCs)" and "Acute Myocardial Infarction (or Myocardial Infarction or AMI or MI)". The endpoints were the left ventricular ejection fraction (LVEF) in animal model with AMI.
RESULTS
In total, 5 studies were included in the meta-analysis. Pooled analysis indicated a significant LVEF difference at 4 weeks follow-up between MSCs + ATOR combine group and MSCs alone group (95 % CI, 9.09-13.62 %; P < 0.01) with heterogeneity (P = 0.28; P >0.05) and inconsistency (I(2): 22 %).
CONCLUSIONS
Atorvastatin can enhance the existing effects of MSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.
Topics: Animals; Atorvastatin; Chi-Square Distribution; Combined Modality Therapy; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mesenchymal Stem Cell Transplantation; Myocardial Infarction; Myocardium; Recovery of Function; Regeneration; Stroke Volume; Time Factors; Ventricular Function, Left
PubMed: 26667804
DOI: 10.1186/s12872-015-0162-6 -
Journal of Cardiovascular Pharmacology Jun 2019Antihypertensive drugs (AHTDs) and statins are frequently administered together, but there is uncertainty on whether the presence of one affects the main effects of the... (Meta-Analysis)
Meta-Analysis
Antihypertensive drugs (AHTDs) and statins are frequently administered together, but there is uncertainty on whether the presence of one affects the main effects of the other. This systematic review and meta-analysis assessed the effects of co-administered AHTDs and statins on blood pressure (BP) and cholesterol. MEDLINE, Cochrane Central Register of Controlled Trials and drug regulatory agency websites were searched, until January 2018. Twelve double-blind randomized controlled trials that allocated adults with or without hypertension and/or hyperlipidemia (n = 4434) to fixed doses of AHTD alone, statin alone and both drugs together, for ≥4 weeks, were included. BP lowering was similar with AHTD + statin compared with AHTD alone [systolic BP -0.1 mm Hg, 95% confidence interval (CI), -1.0 to 0.8, and diastolic BP -1.0 mm Hg, 95% CI, -2.3 to -0.2]. AHTD + statin compared with statin alone resulted in small reduction in low-density lipoprotein cholesterol (-3.9 mg/dL, 95% CI, -6.1 to -1.7), and this effect was largely associated with co-administration of amlodipine and atorvastatin or rosuvastatin. There was no difference in safety outcomes. Overall, it can be concluded that there is no clinically important difference in the effects of AHTDs and statins whether used separately or together for reduction in BP and low-density lipoprotein cholesterol.
Topics: Antihypertensive Agents; Biomarkers; Blood Pressure; Cholesterol, LDL; Drug Interactions; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31162243
DOI: 10.1097/FJC.0000000000000671 -
The Cochrane Database of Systematic... Jul 2023Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary... (Review)
Review
BACKGROUND
Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary syndrome (PCOS), statins may also exert other beneficial metabolic and endocrine effects, such as reducing testosterone levels. This is an update of a Cochrane Review first published in 2011.
OBJECTIVES
To assess the efficacy and safety of statin therapy in women with PCOS who are not actively trying to conceive.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHLs, and four ongoing trials registers on 7 November 2022. We also handsearched relevant conference proceedings and the reference lists of relevant trials for any additional studies, and we contacted experts in the field for any further ongoing studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated the effects of statin therapy in women with PCOS not actively trying to conceive. Eligible comparisons were statin versus placebo or no treatment, statin plus another agent versus the other agent alone, and statin versus another agent. We performed statistical analysis using Review Manager 5, and we assessed the certainty of the evidence using GRADE methods.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. Our primary outcomes were resumption of menstrual regularity and resumption of spontaneous ovulation. Our secondary outcomes were clinical and physiological measures including hirsutism, acne severity, testosterone levels, and adverse events.
MAIN RESULTS
Six RCTs fulfilled the criteria for inclusion. They included 396 women with PCOS who received six weeks, three months, or six months of treatment; 374 women completed the studies. Three studies evaluated the effects of simvastatin and three studies evaluated the effects of atorvastatin. We summarised the results of the studies under the following comparisons. Statins versus placebo (3 RCTs) One trial measured resumption of menstrual regularity as menstrual cycle length in days. We are uncertain if statins compared with placebo shorten the mean length of the menstrual cycle (mean difference (MD) -2.00 days, 95% confidence interval (CI) -24.86 to 20.86; 37 participants; very low-certainty evidence). No studies reported resumption of spontaneous ovulation, improvement in hirsutism, or improvement in acne. We are uncertain if statins compared with placebo reduce testosterone levels after six weeks (MD 0.06, 95% CI -0.72 to 0.84; 1 RCT, 20 participants; very low-certainty evidence), after 3 months (MD -0.53, 95% CI -1.61 to 0.54; 2 RCTs, 64 participants; very low-certainty evidence), or after 6 months (MD 0.10, 95% CI -0.43 to 0.63; 1 RCT, 28 participants; very low-certainty evidence) Two studies recorded adverse events, and neither reported significant differences between the groups. Statins plus metformin versus metformin alone (1 RCT) The single RCT included in this comparison measured resumption of menstrual regularity as the number of spontaneous menses per six months. We are uncertain if statins plus metformin compared with metformin improves resumption of menstrual regularity (MD 0.60 menses, 95% CI 0.08 to 1.12; 69 participants; very low-certainty evidence). The study did not report resumption of spontaneous ovulation. We are uncertain if statins plus metformin compared with metformin alone improves hirsutism measured using the Ferriman-Gallwey score (MD -0.16, 95% CI -0.91 to 0.59; 69 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.31, 95% CI -0.67 to 0.05; 69 participants; very low-certainty evidence), or testosterone levels (MD -0.03, 95% CI -0.37 to 0.31; 69 participants; very low-certainty evidence). The study reported that no significant adverse events occurred. Statins plus oral contraceptive pill versus oral contraceptive pill alone (1 RCT) The single RCT included in this comparison did not report resumption of menstrual regularity or spontaneous ovulation. We are uncertain if statins plus the oral contraceptive pill (OCP) improves hirsutism compared with OCP alone (MD -0.12, 95% CI -0.41 to 0.17; 48 participants; very low-certainty evidence). The study did not report improvement in acne severity. We are also uncertain if statins plus OCP compared with OCP alone reduces testosterone levels, because the certainty of the evidence was very low (MD -0.82, 95% CI -1.38 to -0.26; 48 participants). The study reported that no participants experienced significant side effects. Statins versus metformin (2 RCTs) We are uncertain if statins improve menstrual regularity compared with metformin (number of spontaneous menses per six months) compared to metformin (MD 0.50 menses, 95% CI -0.05 to 1.05; 1 RCT, 61 participants, very low-certainty evidence). No studies reported resumption of spontaneous ovulation. We are uncertain if statins compared with metformin reduce hirsutism measured using the Ferriman-Gallwey score (MD -0.26, 95% CI -0.97 to 0.45; 1 RCT, 61 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.18, 95% CI -0.53 to 0.17; 1 RCT, 61 participants; very low-certainty evidence), or testosterone levels (MD -0.24, 95% CI -0.58 to 0.10; 1 RCT, 61 participants; very low-certainty evidence). Both trials reported that no significant adverse events had occurred. Statins versus oral contraceptive pill plus flutamide (1 RCT) According to the study report, no participants experienced any significant side effects. There were no available data for any other main outcomes.
AUTHORS' CONCLUSIONS
The evidence for all main outcomes of this review was of very low certainty. Due to the limited evidence, we are uncertain if statins compared with placebo, or statins plus metformin compared with metformin alone, improve resumption of menstrual regularity. The trial evaluating statin plus OCP versus OCP alone reported neither of our primary outcomes. No other studies reported resumption of spontaneous ovulation. We are uncertain if statins improve hirsutism, acne severity, or testosterone. All trials that measured adverse events reported no significant differences between the groups.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hirsutism; Metformin; Acne Vulgaris; Contraceptives, Oral; Testosterone
PubMed: 37462232
DOI: 10.1002/14651858.CD008565.pub3