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      Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials

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          Abstract

          Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with complex etiology and pathophysiology, which remains poorly understood. It affects about 5–10% of women of reproductive age who typically suffer from obesity, hyperandrogenism, ovarian dysfunction, and menstrual irregularity. Indeed, PCOS is the most common cause of anovulatory infertility in industrialized nations, and it is associated with insulin resistance, type 2 diabetes mellitus, and increased cardiovascular risk. Although insulin resistance is not included as a criterion for diagnosis, it is a critical pathological condition of PCOS. The purpose of this systematic review is the analysis of recent randomized clinical trials of inositol(s) in PCOS, in particular myo- and D-chiro-inositol, in order to better elucidate their physiological involvement in PCOS and potential therapeutic use, alone and in conjunction with assisted reproductive technologies, in the clinical treatment of women with PCOS.

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          Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome.

          A Dunaif, K R Segal, W Futterweit … (1989)
          Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of the polycystic ovary syndrome (PCO). However, controversy exists as to whether insulin resistance results from PCO or the obesity that is frequently associated with it. Thus, we determined in vivo insulin action on peripheral glucose utilization (M) and hepatic glucose production (HGP) with the euglycemic glucose-clamp technique in obese (n = 19) and nonobese (n = 10) PCO women and age- and body-composition-matched normal ovulatory women (n = 11 obese and n = 8 nonobese women). None had fasting hyperglycemia. Two obese PCO women had diabetes mellitus, established with an oral glucose tolerance test; no other women had impairment of glucose tolerance. However, the obese PCO women had significantly increased fasting and 2-h glucose levels after an oral glucose load and increased basal HGP compared with their body-composition-matched control group. There were statistically significant interactions between obesity and PCO in fasting glucose levels and basal HGP (P less than .05). Steady-state insulin levels of approximately 100 microU/ml were achieved during the clamp. Insulin-stimulated glucose utilization was significantly decreased in both PCO groups whether expressed per kilogram total weight (P less than .001) or per kilogram fat free mass (P less than .001) or when divided by the steady-state plasma insulin (l) level (M/l, P less than .001). There was residual HGP in 4 of 15 obese PCO, 0 of 11 obese normal, 2 of 10 nonobese PCO, and 0 of 8 nonobese normal women. The metabolic clearance rate of insulin did not differ in the four groups. We conclude that 1) PCO women have significant insulin resistance that is independent of obesity, changes in body composition, and impairment of glucose tolerance, 2) PCO and obesity have a synergistic deleterious effect on glucose tolerance, 3) hyperinsulinemia in PCO is not the result of decreased insulin clearance, and 4) PCO is associated with a unique disorder of insulin action.
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            Metformin in polycystic ovary syndrome: systematic review and meta-analysis.

            Christopher J. Lord, J. Norman, Ingrid Flight (2003)
            To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome. Systematic review and meta-analysis. Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent. 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence. Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome. Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance. Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.
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              Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials.

              G Carlomagno, F Facchinetti, G Dante … (2012)
              Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re-establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS.
              Article 0 comments Cited 48 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Endocrinol
                Journal ID (iso-abbrev): Int J Endocrinol
                Journal ID (publisher-id): IJE
                Title: International Journal of Endocrinology
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1687-8337
                ISSN (Electronic): 1687-8345
                Publication date (Print): 2016
                Publication date (Electronic): 23 October 2016
                Volume: 2016
                Electronic Location Identifier: 1849162
                Affiliations
                1Department of Medical Sciences, IPUS-Institute of Higher Education, Chiasso, Switzerland
                2Department of Medicine and Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA
                3Clinic of Endocrinology, Alexandrovska University Hospital, Medical University, Sofia, Bulgaria
                4IAKENTRO, Infertility Treatment Center, Thessaloniki, Greece
                5Mother-Infant Department, University of Modena and Reggio Emilia, Modena, Italy
                Author notes
                *Vittorio Unfer: vunfer@ 123456gmail.com

                Academic Editor: Michael Horowitz

                Author information
                http://orcid.org/0000-0002-1805-3181
                Article
                DOI: 10.1155/2016/1849162
                PMC ID: 5097808
                PubMed ID: 27843451
                SO-VID: 2ca9cfa5-867c-457c-b9bb-d105d4caf41e
                Copyright © Copyright © 2016 Vittorio Unfer et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 6 July 2016
                Date accepted : 22 September 2016
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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