Metformin is a reasonable first-line treatment option for non-obese women with infertility related to anovulatory polycystic ovary syndrome – A meta-analysis of randomised trials

Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women in reproductive age. It is estimated that it affects about 5-10% of women aged 18-44. This disease is associated with reproductive dysfunction and metabolic disorders. According to the American Society for Reproductive Medicine (ASRM) 2018 guidelines, the first line treatment for PCOS are lifestyle adjustments, including dietary control and exercise. Hence a lot of research on the diet that is most appropriate for this group of people. Material and methods: PubMed research base was searched using the following keywords: diet, pcos, policystic ovary syndrome in 2017-2021. Results: The diet of women with PCOS is poorly composed, and dietary errors may affect the metabolic disorders occurring in these patients. Women with PCOS tend to have insufficient intakes of vitamin D, fiber, and vitamin B9, as well as excessive sodium intake. Mediterranean, ketogenic, low-carbohydrate, low-glycemic, low-AGE and pod-based diets positively affect this disease in various ways. Conclusions: PCOS is a very diverse disease that affects a large number of women around the world. Changing your lifestyle, including diet and exercise, is the first line treatment. This is why creating the best diet for these patients is extremely important. Current discoveries are very promising and give hope to create a model of nutrition that will be the best for these women. Large, multicentre randomized trials are still needed to develop diets that are appropriate for different patients because the disease picture is heterogeneous.

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Metformin in first-line treatment in sterile polycystic ovary syndrome patients with neither obesity non insulin resistance

Fertility and Sterility ◽

10.1016/j.fertnstert.2007.07.629 ◽

2007 ◽

Vol 88 ◽

pp. S183

Author(s):

M. Attie ◽

E. Lombardi ◽

L. Sicaro ◽

E. Young

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Line Treatment ◽

First Line ◽

Ovary Syndrome ◽

First Line Treatment

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Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-0110 ◽

2005 ◽

Vol 90 (7) ◽

pp. 4068-4074 ◽

Cited By ~ 176

Author(s):

Stefano Palomba ◽

Francesco Orio ◽

Angela Falbo ◽

Francesco Manguso ◽

Tiziana Russo ◽

...

Keyword(s):

Polycystic Ovary ◽

Clomiphene Citrate ◽

Controlled Clinical Trial ◽

Line Treatment ◽

First Line ◽

Ovary Syndrome ◽

Double Blind ◽

Group A ◽

Group B ◽

First Line Treatment

Abstract Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001). Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

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Comment on: Effects of Bariatric Surgery on the Menstruation and Reproductive Related Hormones of Obese Women without Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis

Surgery for Obesity and Related Diseases ◽

10.1016/j.soard.2021.11.007 ◽

2021 ◽

Author(s):

Judy Y. Chen

Keyword(s):

Systematic Review ◽

Bariatric Surgery ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Meta Analysis ◽

Obese Women ◽

Ovary Syndrome

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Update on polycystic ovary syndrome

Clinical and Experimental Reproductive Medicine ◽

10.5653/cerm.2020.04329 ◽

2021 ◽

Author(s):

Jin Ju Kim

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Meta Analysis ◽

Daily Practice ◽

Antral Follicle ◽

Reproductive Age ◽

Lifestyle Modifications ◽

First Line ◽

Ovary Syndrome ◽

Wide Range

Polycystic ovary syndrome (PCOS) is a common disorder in reproductive-age women. In 2018, an international evidence-based guideline announced recommendations spanning a wide range of issues on the assessment and management of PCOS. From the 166 recommendations, the present study reviews those that are of particular clinical relevance for daily practice and introduces other relevant studies that have been published since the global guideline. The 2018 guideline increased the antral follicle count cutoff for the diagnosis of PCOS from 12 to 20 when using a high-frequency probe. Hirsutism was defined as having a score of ≥4–6 based on a lower percentile of 85%–90% or cluster analysis, which was lower than the traditionally used 95th percentile-based cutoff. The diagnosis of PCOS in adolescents is challenging, and irregular menstruation was defined carefully according to years from menarche. The use of ultrasonography for the diagnosis of PCOS was restricted to those 8 years after menarche. As medication for non-fertility indications, combined oral contraceptives are the first-line drug. Metformin, in addition to lifestyle modifications, should be considered for adult patients with a body mass index ≥25 kg/m2 for the management of weight and metabolic outcomes. An aromatase inhibitor is the recommended first-line medication for ovulation induction, a subsequent individual patient data meta-analysis also reported the same conclusion. Whether the new global guideline will be fully adopted by many specialists and change clinical practice is open to question. Further studies are needed to better understand and manage PCOS patients well.

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Circulating resistin and follistatin levels in obese and non-obese women with polycystic ovary syndrome: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0246200 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0246200

Author(s):

Tahereh Raeisi ◽

Hossein Rezaie ◽

Mina Darand ◽

Akram Taheri ◽

Nazila Garousi ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Meta Analysis ◽

Significant Heterogeneity ◽

Obese Women ◽

Ovary Syndrome ◽

Obesity Status ◽

Significant Difference ◽

Mean Differences ◽

Stratified Analysis

This meta-analysis was performed to resolve the inconsistencies regarding resistin and follistatin levels in women with polycystic ovary syndrome (PCOS) by pooling the available evidence. A systematic literature search using PubMed and Scopus was carried out through November 2020 to obtain all pertinent studies. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between the levels of resistin and follistatin with PCOS in the overall and stratified analysis by obesity status. A total of 47 publications, 38 for resistin (2424 cases; 1906 controls) and 9 studies for follistatin (815 cases; 328 controls), were included in the meta-analysis. Resistin levels were significantly higher in PCOS women compared with non-PCOS controls (WMD = 1.96 ng/ml; 95%CI = 1.25–2.67, P≤0.001) as well as in obese PCOS women vs. obese controls, and in non-obese PCOS women compared with non-obese controls, but not in obese PCOS vs. non-obese PCOS patients,. A significantly increased circulating follistatin was found in PCOS patients compared with the controls (WMD = 0.44 ng/ml; 95%CI = 0.30–0.58, P≤0.001) and in non-obese PCOS women compared with non-obese controls and in obese PCOS women vs. obese controls, but, no significant difference in follistatin level was observed in obese PCOS compared with non-obese PCOS women. Significant heterogeneity and publication bias was evident for some analyses. Circulating levels of resistin and follistatin, independent of obesity status, are higher in women with PCOS compared with controls, showing that these adipokines may contribute to the pathology of PCOS.

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