Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review

Palomba, Stefano; Falbo, Angela; Zullo, Fulvio; Orio, Francesco

doi:10.1210/er.2008-0030

Cited by 361 publications

(339 citation statements)

References 452 publications

(248 reference statements)

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“…Metformin also has beneficial effects on endometrial abnormalities, such as hyperplasia and cancerous lesions (Palomba et al 2009). Expression of the insulin receptor gene is regulated during the menstrual cycle, enabling insulin to inhibit stromal cell decidualization (Lockwood et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis

et al. 2013

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Adenomyosis is a finding that is associated with dysmenorrhea and heavy menstrual bleeding, associated with PI3K/AKT signaling overactivity. To investigate the effect of metformin on the growth of eutopic endometrial stromal cells (ESCs) from patients with adenomyosis and to explore the involvement of AMP-activated protein kinase (AMPK) and PI3K/AKT pathways. Primary cultures of human ESCs were derived from normal endometrium (normal endometrial stromal cells (N-ESCs)) and adenomyotic eutopic endometrium (adenomyotic endometrial stroma cells (A-ESCs)). Expression of AMPK was determined using immunocytochemistry and western blot analysis. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assays were used to determine the effects of metformin and compound C on ESCs and also to detect growth and proliferation of ESCs. AMPK and PI3K/AKT signaling was determined by western blotting. A-ECSs exhibited greater AMPK expression than N-ESCs. Metformin inhibited proliferation of ESCs in a concentration-dependent manner. The IC 50 was 2.45 mmol/l for A-ESCs and 7.87 mmol/l for N-ESCs. Metformin increased AMPK activation levels (p-AMPK/AMPK) by 2.0G0.3-fold in A-ESCs, 2.3-fold in A-ESCs from the secretory phase, and 1.6-fold in the proliferation phase. The average reduction ratio of 17b-estradiol on A-ESCs was 2.1G0.8-fold in proliferative phase and 2.5G0.5-fold in secretory phase relative to the equivalent groups not treated with 17b-estradiol. The inhibitory effects of metformin on AKT activation (p-AKT/AKT) were more pronounced in A-ESCs from the secretory phase (3.2-fold inhibition vs control) than in those from the proliferation phase (2.3-fold inhibition vs control). Compound C, a selective AMPK inhibitor, abolished the effects of metformin on cell growth and PI3K/AKT signaling. Metformin inhibits cell growth via AMPK activation and subsequent inhibition of PI3K/AKT signaling in A-ESCs, particularly during the secretory phase, suggesting a greater effect of metformin on A-ESCs from secretory phase.

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Section: Discussionmentioning

confidence: 99%

Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis

et al. 2013

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“…Treatment with metformin increases insulin sensitivity and improves ovulatory function in PCOS (61), whereas androgen levels and hirsutism scores are only mildly improved or unchanged (61,74). The first-line treatment modalities for pre-diabetes are lifestyle intervention and metformin treatment (75).…”

Section: Cardiometabolic Disease In Pcosmentioning

confidence: 99%

“…Treatment with metformin for 6 months or less had a limited effect on weight loss (74), whereas 12 months treatment induced a median weight loss of 3 kg (64). Decreased adipokine and ghrelin levels during metformin treatment could induce weight loss (74,76), but this hypothesis needs further testing.…”

Section: Cardiometabolic Disease In Pcosmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome

Glintborg

Andersen

2017

European Journal of Endocrinology

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Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long-term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin resistance. Available data from register-based and data linkage studies support that metabolic-vascular and thyroid diseases, asthma, migraine, depression and cancer are diagnosed more frequently in PCOS, whereas fracture risk is decreased. Drug prescriptions are significantly more common in PCOS than controls within all diagnose categories including antibiotics. The causal relationship between PCOS and autoimmune disease represents an interesting new area of research. PCOS is a lifelong condition and long-term morbidity could be worsened by obesity, sedentary way of life, Western-style diet and smoking, whereas lifestyle intervention including weight loss may partly or fully resolve the symptoms of PCOS and could improve the long-term prognosis. In this review, the possible implications of increased morbidity for the clinical and biochemical evaluation of patients with PCOS at diagnosis and follow-up is further discussed along with possible modifying effects of medical treatment.

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“…The heterogeneity of PCOS makes it difficult to elucidate the mechanism. However, insulin resistance has been reported to be associated with a greater risk of anovulation in women with PCOS (Palomba et al 2009a(Palomba et al , 2009b. Therefore, this metabolic abnormality might be a key to ovulatory dysfunction in a portion of women with PCOS.…”

Section: Introductionmentioning

confidence: 99%

Intake of Vinegar Beverage Is Associated with Restoration of Ovulatory Function in Women with Polycystic Ovary Syndrome

Kimura

Takashima

et al. 2013

Tohoku J. Exp. Med.

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Polycystic ovary syndrome (PCOS) is one of major causes of irregular menstruation. It is defined as a condition involving the combination of hyperandrogenism and chronic oligomenorrhea or anovulation, and is thought to have a variety of etiologies. Insulin resistance (impaired insulin sensitivity) has been suggested to be one of the etiologies of PCOS. PCOS patients often need to take medication to treat anovulation and infertility. Therefore, it would be beneficial to patients if simple non-pharmacological treatments can be developed. Recently the efficacy of vinegar to improve insulin resistance has been reported. To study the effect of vinegar on metabolic and hormonal indices and ovulatory function in PCOS, seven patients seeking a non-pharmacological treatment for PCOS took a beverage containing 15 g of apple vinegar daily for 90 to 110 days. Ovulation, the menstrual interval, fasting serum glucose level, fasting serum insulin level, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were compared before and after intake of the vinegar beverage. Intake of the vinegar beverage resulted in a decrease of the homeostasis model assessment insulin resistance index (HOMA-R) in six patients, as well as a decrease of the LH/FSH ratio in five of seven patients. Ovulatory menstruation was observed within 40 day in four of seven patients. These findings suggest the possibility of vinegar to restore ovulatory function through improving insulin sensitivity in PCOS patients, thus, avoiding pharmacological treatment. Intake of vinegar might reduce medical cost and treatment time for insulin resistance, anovulation, and infertility in patients with PCOS.

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Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review

Cited by 361 publications

References 452 publications

Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis

Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis

MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome

Intake of Vinegar Beverage Is Associated with Restoration of Ovulatory Function in Women with Polycystic Ovary Syndrome

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