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Comparison of metformin plus myoinositol vs metformin alone in PCOS women undergoing ovulation induction cycles: randomized controlled trial.
Agrawal, A, Mahey, R, Kachhawa, G, Khadgawat, R, Vanamail, P, Kriplani, A
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(6):511-514
Abstract
The present study was planned to evaluate the benefit of synergetic effect of Metformin plus Myo-inositol versus Metformin alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction. One hundred and twenty infertile PCOS women were randomized: Group I (n = 60) received Metformin (500 mg) plus Myoinositol(600 mg) three times a day; Group II received Metformin 500 mg three times a day. Subjects were advised to try for spontaneous conception. Those who did not conceive after 3 months, were given three cycles of ovulation induction + intrauterine insemination. Hormonal and biochemical profile parameters were done at baseline and after 3 months of therapy. Primary outcome measure was live birth rate. Secondary outcomes were improvement in menstrual cycle, hormonal and biochemical parameters, spontaneous conception, abortions, multiple pregnancy, and ovarian hyperstimulation syndrome. Baseline demographic, hormonal and biochemical parameters were comparable in two groups. There was a significant improvement in menstrual cycles (cycle length and bleeding days) in Group I as compared to Group II. The improvement in biochemical and hormonal parameters were comparable in the two groups after 3 months. Live birth rate was significantly higher in the Group I as compared to Group II [55% (33/60); 26.67% (16/60); p = .002]. The study concluded significantly higher live birth rate in women receiving the combination as compared to metformin alone.
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Current and future aspects of several adjunctive treatment strategies in polycystic ovary syndrome.
Banaszewska, B, Pawelczyk, L, Spaczynski, R
Reproductive biology. 2019;(4):309-315
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age. PCOS is characterized by hyperandrogenism, menstrual disorders, and polycystic ovarian morphology. PCOS patients have an increased risk of type 2 diabetes, cardiovascular disease, and infertility. The mechanism of PCOS is not yet fully understood, but insulin resistance and genetic factors may play distinct roles in the pathomechanism. There is ongoing research on new therapeutic modalities for women with PCOS. In this minireview, we assessed the evidence for the effectiveness and safety of selected adjunctive agents (metformin, statins, resveratrol, melatonin, and inositols) for the treatment of women with PCOS. Metformin is a safe medication used in PCOS for 25 years that is currently recommended in select PCOS subpopulations, such as adolescents, women with metabolic disorders, and infertility infertile women undergoing ovarian hyperstimulation. Statins are also suggested in PCOS therapy, as these compounds decrease testosterone concentrations, improve lipid profiles, and ameliorate inflammatory reactions. Despite promising results, the role of statins in PCOS management needs to be further validated. Dietary supplements have also been tested in PCOS patients. Resveratrol was shown to decrease total testosterone production and improve fasting insulin but, until recently, only in one randomized study. Data on the therapeutic efficacy of melatonin and inositols on endocrine and metabolic abnormalities are limited and inconclusive. The multifactorial etiology of PCOS makes tailoring of its treatment more demanding, and there is a constant need for causative and effective modes of PCOS therapy.
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The effect of myo-inositol/di-chiro-inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta-analysis.
Bhide, P, Pundir, J, Gudi, A, Shah, A, Homburg, R, Acharya, G
Acta obstetricia et gynecologica Scandinavica. 2019;(10):1235-1244
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Abstract
INTRODUCTION High levels of anti-Mullerian hormone and a high antral follicle count in women with polycystic ovary syndrome, reflecting increased ovarian antral follicles, predisposes them to have a high number of retrieved oocytes with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and an increased risk of ovarian hyperstimulation syndrome. Inositols, which act as insulin sensitizers, have the potential to alter folliculogenesis and the functional ovarian reserve, with subsequent benefits to reproductive outcomes following IVF/ICSI treatment. Published literature is, however, unable to provide definitive evidence of its efficacy. The objective of our review was to evaluate the effect of inositols on anti-Mullerian hormone, antral follicle count and reproductive outcomes in women with polycystic ovary syndrome undergoing IVF/ICSI. MATERIAL AND METHODS We performed a literature search using standard methodology recommended by Cochrane. Randomized controlled trials and non-randomized studies comparing inositols with no treatment, placebo or other treatment were included in the review. Using standard methodology recommended by Cochrane we pooled results using the random effects model; our findings were reported as relative risk or mean differences. PROSPERO registration: CRD42017082275. RESULTS We included 18 trials. The primary outcome was a change in anti-Mullerian hormone and antral follicle count before and after treatment, for which data were unsuitable for meta-analysis. A narrative review showed no consistent direction or size of effect. A meta-analysis for the secondary outcomes showed no evidence of a significant difference between inositol and control groups for any outcome: number of oocytes (mean difference -0.39, 95% confidence interval [CI] -1.11 to 0.33), number of metaphase II oocytes (mean difference 0.29, 95% CI -0.83 to 1.40), number of top grade embryos (risk ratio [RR] 1.02, 95% CI 0.93-1.12), clinical pregnancy rate (RR 1.16, 95% CI 0.87-1.53), and risk of ovarian hyperstimulation syndrome (RR 0.73, 95% CI 0.39-1.37). The quality of evidence was assessed as very low. CONCLUSIONS There is insufficient evidence for an effect of inositols on ovarian reserve markers and to support their use as pretreatment before IVF/ICSI in women with polycystic ovary syndrome.
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Diagnosis of disorders of glucose tolerance in women with polycystic ovary syndrome (PCOS) at a tertiary care center: fasting plasma glucose or oral glucose tolerance test?
Ortiz-Flores, AE, Luque-Ramírez, M, Fernández-Durán, E, Alvarez-Blasco, F, Escobar-Morreale, HF
Metabolism: clinical and experimental. 2019;:86-92
Abstract
BACKGROUND The risk of developing prediabetes and type 2 diabetes (dysglycemia) may be increased in women with PCOS. Whether an oral glucose tolerance test (OGTT) should be performed routinely in all PCOS women at presentation or should be recommended only to a selected subset of patients is still controversial. BASIC PROCEDURES At a tertiary care center, we conducted a retrospective, observational study including 400 women with PCOS submitted to an OGTT. Our primary objective was to assess the diagnostic agreement between two algorithms commonly used for the screening of dysglycemia in these women: i) relying only on fasting plasma glucose (FPG) or ii) considering both fasting and/or 120-min plasma glucose concentrations during an OGTT. We conducted the analysis considering all patients as a whole, and also after stratifying them by body weight, androgen concentrations and age. MAIN FINDINGS The OGTT detected dysglycemia in 24.5% of patients, whereas only 14.3% women would have been diagnosed using FPG levels alone. The latter missed as many as 40% of women with dysglycemia in our series, including all cases of diabetes. Diagnostic agreement between both algorithms was only 0.55 (κ = 0.103; 95% CI: 0.05-0.16). Areas under the receiver operating characteristic curve for dysglycemia were 0.86 (95%CI: 0.81-0.91) for FPG and 0.91 (95%CI = 0.87-0.95) for 120-min plasma glucose during the OGTT. FPG was not accurate in predicting dysglycemia in women with PCOS regardless of the presence of insulin resistance, weight excess, hyperandrogenemia and age. PRINCIPAL CONCLUSIONS Relying on FPG alone is not adequate for the screening of disorders of glucose tolerance in women with PCOS; such diagnosis should rely on the results of an OGTT regardless of age, weight and/or androgen concentrations.
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Zinc status and polycystic ovarian syndrome: A systematic review and meta-analysis.
Abedini, M, Ghaedi, E, Hadi, A, Mohammadi, H, Amani, R
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2019;:216-221
Abstract
Several studies have investigated serum zinc levels in patients with polycystic ovarian syndrome (PCOS), but the results of these studies remain inconclusive. Therefore, to derive a more precise estimation, we conducted a meta-analysis to investigate serum zinc concentrations in women with PCOS in comparison with healthy subjects. Electronic search was performed in PubMed, Scopus, and Google scholar up to April; 4, 2018 without any restriction. Eligible studies that evaluated the levels of zinc status in subjects with PCOS were included. Weighted mean differences (WMDs) with corresponding 95% CIs in serum zinc levels were initially estimated using a random-effects model. Eight studies, measuring circulating zinc levels in 552 PCOS and 464 control subjects, were included. Pooled effect size suggested that serum zinc levels in women with PCOS were not statistically different than their controls (WMD = -4.43 mg/dL; 95% CI = [-10.30, 1.44]; P = 0.139). Exclusion of one study revealed that women with PCOS significantly have lower serum zinc levels compared to healthy controls (WMD: -6.60 mg/dL; 95% CI = [-12.43, -0.76], P = 0.027). Our study indicated that circulating zinc levels in women with PCOS were significantly lower than those in healthy controls when detailed analysis is conducted. Large scale studies are needed to elucidate clear relation between zinc status and etiology of PCOS.
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Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials.
Facchinetti, F, Orrù, B, Grandi, G, Unfer, V
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(3):198-206
Abstract
Metformin (MET), the most commonly used insulin sensitizer, is the reference off-label drug for the treatment of polycystic ovary syndrome (PCOS), worldwide. However, its use may be limited mainly by gastrointestinal adverse effects. Myo-inositol (MI), a well-recognized food supplement, also represents an evidence-based treatment for PCOS women, popular in many countries. Our aim is to provide a systematic review of the literature and a meta-analysis which compares these two treatments, for their short-term efficacy and safety in PCOS patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). RCTs were identified from 1994 through 2017 using MEDLINE, Cochrane Library, PubMed, and ResearchGate. Included studies were limited to those one directly comparing MET to MI on several hormones changes. Standardized mean difference (SMD) or risk ratios (RRs) with 95% CIs were calculated. Changes in fasting insulin was the main outcome of measure. Six trials with a total of 355 patients were included. At the end of treatment, no difference between MET and MI was found on fasting insulin (SMD=0.08 µU/ml, 95% CI: -0.31-0.46, p=.697), HOMA index (SMD =0.17, 95% CI: -0.53-0.88, p=.635), testosterone (SMD= -0.01, 95% CI: -0.24-0.21, p=.922), SHBG levels (SMD= -0.50 nmol/l, 95% CI: -1.39-0.38, p=.263) and body mass index (BMI) (SMD= -0.22, 95% CI: -0.60-0.16, p=.265). There was strong evidence of an increased risk of adverse events among women receiving MET compared to those receiving MI (RR =5.17, 95% CI: 2.91-9.17, p<.001). No differences were found in the effect of MET and MI on short-term hormone changes. The better tolerability of MI makes it more acceptable for the recovery of androgenic and metabolic profile in PCOS women.
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Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial.
Mendoza, N, Diaz-Ropero, MP, Aragon, M, Maldonado, V, Llaneza, P, Lorente, J, Mendoza-Tesarik, R, Maldonado-Lobon, J, Olivares, M, Fonolla, J
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(8):695-700
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Abstract
The purpose of this study was to evaluate the effect of two doses of D-chiro-inositol (DCI) in combination with Myo-inositol (MYO) in women with PCOS undergoing ICSI. This was a multicenter controlled, randomized, double-blind parallel group study with two MYO-DCI formulations for 12 weeks. The study group (SG) was administered 550 mg of MYO + 150 mg of DCI twice daily; the control group (CG) was administered 550 mg of MYO + 13.8 mg of DCI twice daily. The participants comprised 60 women with PCOS undergoing ICSI. At baseline, no differences were found between the two groups regarding age, BMI, HOMA-IR or testosterone levels. The pregnancy and live birth rates were significantly higher in the SG than in the CG (65.5 vs. 25.9 and 55.2 vs. 14.8, respectively) [risk ratio (RR) = 0.4; 95%CI (0.2, 0.79); p = .003 and RR = 0.27; 95%CI (0.10, 0.70); p = .002 respectively]. The risk of ovarian hyperstimulation syndrome (OHSS) was lower in the SG (3.44 vs. 18.5%, p = .07). The combination of MYO-DCI at high doses of DCI improves the pregnancy rates and reduces the risk of OHSS in women with PCOS undergoing ICSI.
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The impact of a standardized micronutrient supplementation on PCOS-typical parameters: a randomized controlled trial.
Hager, M, Nouri, K, Imhof, M, Egarter, C, Ott, J
Archives of gynecology and obstetrics. 2019;(2):455-460
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PURPOSE To evaluate whether a micronutrient supplementation preparation that includes a high amount of omega-3 unsaturated acids, other anti-oxidants and co-enzyme Q10 would have an impact on specific serum parameters in women with polycystic ovary syndrome (PCOS). METHODS The study was designed as a monocentral, randomized, controlled, double-blinded trial, from June 2017 to March 2018 (Clinical Trials ID: NCT03306745). Sixty women with PCOS were assigned to either the "multinutrient supplementation group" (one unlabeled soft capsule containing omega-3 fatty acids and one unlabeled tablet containing folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, for 3 months) or the "control group" (two unlabeled soft capsules containing 200 μg folic acid each, for 3 months). The main outcome parameters were anti-Mullerian hormone (AMH), total testosterone, and androstenedione. In addition, the focus was on luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, sexual hormone-binding globulin (SHBG), and estradiol. RESULTS In the multinutrient supplementation group, the LH:FSH ratio (2.5 ± 1.1 versus 1.9 ± 0.5, p = 0.001), testosterone (0.50 ± 0.19 versus 0.43 ± 0.15, p = 0.001), and AMH (8.2 ± 4.2 versus 7.3 ± 3.6, p < 0.001) declined significantly, whereas the other parameters, namely estradiol, LH, FSH, androstenedione, and SHBG remained stable. CONCLUSION A micronutrient supplementation that includes omega-3 fatty acids, folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, given for a minimum of 3 months, is beneficial for women with PCOS in terms of PCOS-specific parameters (LH:FSH ratio, serum testosterone and serum AMH).
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Exercise, or exercise and diet for the management of polycystic ovary syndrome: a systematic review and meta-analysis.
Kite, C, Lahart, IM, Afzal, I, Broom, DR, Randeva, H, Kyrou, I, Brown, JE
Systematic reviews. 2019;(1):51
Abstract
BACKGROUND Typically, management of PCOS focuses on lifestyle changes (exercise and diet), aiming to alleviate symptoms, and lower the associated risk of type 2 diabetes and cardiovascular disease. Our objective was to analyse evidence on the effectiveness of exercise in the management of PCOS, when compared to (i) usual care, (ii) diet alone, and (iii) exercise combined with diet, and also exercise combined with diet, compared to (i) control or usual care and (ii) diet alone. METHODS Relevant databases were searched (June 2017) with no time limit for trial inclusion. Eligible trials employed a randomised or quasi-randomised design to measure the chronic effects of exercise, or exercise and diet in women with PCOS. RESULTS Searches returned 2390 articles; of those, 27 papers from 18 trials were included. Results are presented as mean difference (MD) and 95% confidence intervals (95% CI). Compared with control, exercise had a statistical effect on change from baseline fasting insulin (MD - 2.44 μIU/mL, 95% CIs - 4.24 to - 0.64; very low-quality evidence), HOMA-IR (- 0.57, - 0.99 to - 0.14; very low-quality evidence), total cholesterol (- 5.88 mg/dL, - 9.92 to - 1.83; low-quality evidence), LDL cholesterol (- 7.39 mg/dL, - 9.83 to - 4.95; low-quality evidence), and triglycerides (- 4.78 mg/dL, - 7.52 to - 2.05; low-quality evidence). Exercise also improved VO2 max (3.84 ml/kg/min, 2.87 to 4.81), waist circumference (- 2.62 cm, - 4.13 to - 1.11), and body fat percentage (- 1.39%, - 2.61 to - 0.18) when compared with usual care. No effect was found for change value systolic/diastolic blood pressure, fasting glucose, HDL cholesterol (all low-quality evidence), or waist-to-hip ratio. Many favourable change score findings were supported by post-intervention value analyses: fasting insulin (- 2.11 μIU/mL, - 3.49 to - 0.73), total cholesterol (- 6.66 mg/dL, - 11.14 to - 2.17), LDL cholesterol (- 6.91 mg/dL, - 12.02 to - 1.80), and VO2 max (5.01 ml/kg/min, 3.48 to 6.54). Statistically lower BMI (- 1.02 kg/m2, - 1.81 to - 0.23) and resting heart rate (- 3.26 beats/min - 4.93 to - 1.59) were also revealed in post-intervention analysis. Subgroup analyses revealed the greatest improvements in overweight/obese participants, and more outcomes improved when interventions were supervised, aerobic in nature, or of a shorter duration. Based on limited data, we found no differences for any outcome between the effects of exercise and diet combined, and diet alone. It was not possible to compare exercise vs diet or exercise and diet combined vs diet. CONCLUSION Statistically beneficial effects of exercise were found for a range of metabolic, anthropometric, and cardiorespiratory fitness-related outcomes. However, caution should be adopted when interpreting these findings since many outcomes present modest effects and wide CIs, and statistical effects in many analyses are sensitive to the addition/removal of individual trials. Future work should focus on rigorously designed, well-reported trials that make comparisons involving both exercise and diet. SYSTEMATIC REVIEW REGISTRATION This systematic review was prospectively registered on the Prospero International Prospective Register of Systematic Reviews ( CRD42017062576 ).
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Nonpharmacologic Management of Symptoms in Females With Polycystic Ovary Syndrome: A Narrative Review.
Speelman, DL
The Journal of the American Osteopathic Association. 2019;(1):25-39
Abstract
Polycystic ovary syndrome is the most common hormone disorder in females of reproductive age, affecting reproductive, metabolic, and cardiovascular health. With an unknown cause and a spectrum of common signs and symptoms, diagnosis is based on consensus criteria, and treatment options often target individual symptoms, with variable effectiveness. Safe, effective complementary and alternative therapies can be used to manage symptoms. The first-line intervention is lifestyle modification, including weight loss when appropriate, with caloric restriction and exercise to maintain a healthy weight. Low-carbohydrate and/or low-glycemic index diets can provide additional benefits, and nutritional supplements may be useful adjuncts. The recommended physical activity regimen should include both aerobic and resistance exercise.