Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.
Objective
Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.
Methods
The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).
Results
Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).
Conclusion
Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.
PMID 36703143 36703143 DOI 10.1186/s12958-023-01055-z 10.1186/s12958-023-01055-z
Cite this article
Greff, D., Juhász, A. E., Váncsa, S., Váradi, A., Sipos, Z., Szinte, J., Park, S., Hegyi, P., Nyirády, P., Ács, N., Várbíró, S., & Horváth, E. M. (2023). Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reproductive biology and endocrinology : RB&E, 21(1), 10. https://doi.org/10.1186/s12958-023-01055-z
Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10. doi:10.1186/s12958-023-01055-z
Greff, D., et al. "Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials." Reproductive biology and endocrinology : RB&E, vol. 21, no. 1, 2023, pp. 10.
Is there a difference in live birth rates at 24 months between infertile women with polycystic ovary syndrome (PCOS) who have normal versus abnormal glucose metabolism? Abnormal glucose metabolism did not significantly reduce live birth rates but was associated with increased obstetric complications. Women with PCOS are often at increased risk of glucose metabolism disorders. However, evidence about the impact of these disorders on pregnancy outcomes remains limited, particularly in Asian populations. This prospective cohort study was conducted at a reproductive care centre in Vietnam from June 2020 to August 2024. A total of 1208 women were enrolled. PARTICIPANTS/MATERIALS Eligible participants were infertile women aged 18-40 years diagnosed with PCOS (Rotterdam criteria). Comprehensive assessments included medical history, anthropometric measurements, endocrine evaluations, fasting plasma glucose (FPG), glycosylated haemoglobin (HbAlc), and oral glucose tolerance tests (OGTT). Participants were categorized into normal or abnormal glucose metabolism groups and monitored for live birth outcomes at 24 months from the first visit. MAIN Live birth rates at 24 months were comparable between women with normal versus abnormal glucose metabolism (52.7% vs 48.2%, P = 0.12). However, obstetric complications, including gestational diabetes mellitus (15.2% vs 28.0%, P < 0.001) and hypertensive disorders of pregnancy (2.3% vs 9.0%, P < 0.001), were more common in the group with abnormal glucose metabolism. In women who conceived naturally, greater waist circumference and higher Homeostatic Model Assessment of Insulin Resistance index were significantly associated with lower odds of live birth, whereas the presence of hyperandrogenism was associated with higher odds of live birth. No factors were significantly associated with live birth in the group that conceived via ovulation induction plus IUI. In the group that conceived through IVF or IVM, a higher BMI was significantly associated with a lower live birth rate. LIMITATIONS This single-centre study was conducted exclusively on infertile women from South-East Asia who had PCOS, potentially limiting generalizability to other populations. Additionally, metabolic assessments were only performed at baseline, preventing evaluation of longitudinal changes and their dynamic effects on reproductive outcomes. While no significant difference in live birth rates was observed between PCOS women with normal and abnormal glucose metabolism, the abnormal glucose metabolism group experienced higher rates of gestational complications. These findings underscore the importance of preconception metabolic screening and tailored fertility strategies that include targeted interventions to optimize reproductive and maternal outcomes in women with PCOS. This study was supported by My Duc Hospital. Lan N. Vuong reports funding from the Vietnam National Foundation for Science and Technology Development (NAFOSTED; grant number FWO.108-2022.01); Speaker and conference fees; speaker and conference fees as well as a grant; speaker, conference, and scientific board fees outside the submitted work. All other authors declare no conflicts of interest. NCT04364087.
Ahsan M et al., 2025·The Indian journal of medical research
Background & objectives Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterised by menstrual irregularities, hirsutism, acne, obesity, infertility, and other features adversely affecting the quality of life of women of childbearing age. Besides lifestyle modifications, limited pharmacological treatments have been used to manage the symptoms of PCOS. This meta-analysis was conducted to evaluate a novel pharmacological approach, sodium glucose cotransporter-2 inhibitors (SGLT2i), in PCOS. Methods Electronic databases were searched systematically for literature published before November 2024. Randomised controlled trials (RCTs) evaluating SGLT2i alone or in combination in women diagnosed with PCOS, based on the Rotterdam criteria, were included in the meta-analysis. Preclinical studies, and non-randomised trials, were excluded. Quality of studies was assessed using RoB 2.0. Meta-analysis was performed for change in anthropometry, reproductive hormone levels, glycaemic and cardiometabolic indices. Adverse events (AEs) were also compared between the SGLT2i and control groups, using RevMan 5.4.1. Mean difference using the inverse-variance method and 95% confidence interval was used as a measure of effect size of continuous variables, while odds ratio (OR)using the Mantel-Haenszel method (M-H) with 95% confidence interval was calculated to analyse dichotomous variables. P value less than 0.5 was the cut-off for significance. Trial sequential analysis (TSA) was conducted to test the conventional and required information size (RIS) boundaries. The meta-analysis was registered in PROSPERO (CRD42024608736). Results Five RCTs with 'low' risk of bias, including 205 patients with PCOS, receiving SGLT2i (empagliflozin, licogliflozin, dapagliflozin, and canagliflozin alone and in combination with metformin) or control (placebo, metformin, or exenatide) were evaluated in the meta-analysis. SGLT2i significantly reduced total testosterone (mean difference=-0.10 [-0.19, -0.01], P=0.03), free androgen index (mean difference = -0.61 [-1.16, -0.05], P=0.03), and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (mean difference = -0.38 [-0.75, -0.02], P=0.04). Total cholesterol (mean difference=0.13 [0.01, 0.26], P=0.04) and low-density cholesterol (MD=0.18 [0.06, 0.31], P=0.003) increased with SGLT2i use. Genitourinary AEs were more common in the SGLT2i group (OR=10.88 [1.33, 89.14], P= 0.03). On performing TSA, the Z-curve did not cross the RIS boundary of 80 per cent power. Interpretation & conclusions The findings of this meta-analysis suggest that SGLT2i improves the hormonal and glycaemic indices in patients with PCOS. It can prove to be a safe alternative in patients not responding to or intolerant of standard pharmacological treatments.
Brand KM et al., 2025·Women's health (London, England)
Influential guidelines have supported the role of metformin in the management of polycystic ovary syndrome (PCOS) for a number of years. However, regulatory approvals for this therapeutic indication are still exceptional and exist only in a few countries, including for the originator, Glucophage®. PCOS is an insulin-resistant state, which drives hyperandrogenism and anovulatory infertility. The metabolic action of metformin involves amelioration of insulin resistance, which helps to resolve hormonal and metabolic disturbances and increases ovulation, pregnancy, and live birth rates relative to placebo. A combination of metformin with clomifene citrate (another widely used treatment for PCOS) is more effective than either alone and is a useful option in women with clomifene-resistant PCOS. Combining metformin with letrozole (1st-line agent for ovulation induction in women with PCOS and no other infertility risk factors) is not more effective than letrozole alone. Continuing metformin to the end of the 1st trimester at an effective dose (e.g. 1000-2000 mg/day) may help to reduce the rate of miscarriages. Metformin also has an adjunctive role in women with PCOS receiving assisted reproduction technology (ART) using the long gonadotrophin-releasing hormone agonist protocol, where it appears to increase the pregnancy rate and to reduce the risk of ovarian hyperstimulation syndrome. There is no role for metformin in women receiving short ART protocols. Where a successful pregnancy is achieved, metformin is generally safe for the mother and neonate. Further research is needed to define with greater precision the optimal dosage and times to initiate and discontinue metformin in women with PCOS who achieve pregnancy.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases among women of reproductive age and is associated with many metabolic manifestations, such as obesity, insulin resistance (IR) and hyperandrogenism. The underlying pathogenesis of these metabolic symptoms has not yet been fully elucidated. With the application of metabolomics techniques, a variety of metabolite changes have been observed in the serum and follicular fluid (FF) of PCOS patients and animal models. Changes in metabolites result from the daily diet and occur during uncommon physiological routines. However, some of these metabolite changes may provide evidence to explain possible mechanisms and new approaches for prevention and therapy. This article reviews the pathogenesis of PCOS metabolic symptoms and the relationship between metabolites and the pathophysiology of PCOS. Furthermore, the potential clinical application of some specific metabolites will be discussed.