The Role of Metformin in Metabolic Disturbances during Pregnancy: Polycystic Ovary Syndrome and Gestational Diabetes Mellitus

Rojas, Joselyn; Chávez-Castillo, Mervin; Bermúdez, Valmore

doi:10.1155/2014/797681

Cited by 18 publications

(9 citation statements)

References 166 publications

(178 reference statements)

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“…In recent years, MF therapy has become widely used for correction of the metabolic and hormonal impairments in women with PCOS and for restoration of their reproductive functions [ 85 , 108 , 109 , 110 ], including the improvement of IVF/ICSI outcomes in PCOS [ 111 , 112 , 113 , 114 ]. MF is most effective in treating PCOS patients with the metabolic disorders such as T2DM, obesity, dyslipidemia, and severe IR [ 85 , 115 , 116 ]. This is majorly attributed to the alleviation of negative effects of these disorders on the female reproduction by MF, increased tissues sensitivity to insulin, improved lipid and glucose metabolism and cell metabolism, and reduced inflammation and oxidative stress in the ovaries as well as in other tissues.…”

Section: Metformin and Polycystic Ovary Syndromementioning

confidence: 99%

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

2021

Pharmaceuticals

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Metformin (MF), a first-line drug to treat type 2 diabetes mellitus (T2DM), alone and in combination with other drugs, restores the ovarian function in women with polycystic ovary syndrome (PCOS) and improves fetal development, pregnancy outcomes and offspring health in gestational diabetes mellitus (GDM) and T2DM. MF treatment is demonstrated to improve the efficiency of in vitro fertilization and is considered a supplementary drug in assisted reproductive technologies. MF administration shows positive effect on steroidogenesis and spermatogenesis in men with metabolic disorders, thus MF treatment indicates prospective use for improvement of male reproductive functions and fertility. MF lacks teratogenic effects and has positive health effect in newborns. The review is focused on use of MF therapy for restoration of female and male reproductive functions and improvement of pregnancy outcomes in metabolic and endocrine disorders. The mechanisms of MF action are discussed, including normalization of metabolic and hormonal status in PCOS, GDM, T2DM and metabolic syndrome and restoration of functional activity and hormonal regulation of the gonadal axis.

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Section: Metformin and Polycystic Ovary Syndromementioning

confidence: 99%

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

2021

Pharmaceuticals

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“…Available animal studies suggest that metformin does not have teratogenic or carcinogenic effects even at very high doses of 600–1500 mg/kg/day [ 85 ]. A Brazilian group demonstrated that metformin had the potential to cause deoxyribonucleic acid (DNA) damage in vitro in cells of Chinese Hamster ovary (CHO-K1), but not in vivo in mice [ 86 ].…”

Section: Concerns With Fetal Exposure To Metforminmentioning

confidence: 99%

Metformin in the management of diabetes during pregnancy and lactation

Priya

Kalra

2018

DIC

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This review explores the current place of metformin in the management of gestational diabetes (GDM) and type 2 diabetes during pregnancy and lactation. The rationale and basic pharmacology of metformin usage in pregnancy is discussed along with the evidence from observational and randomized controlled trials in women with GDM or overt diabetes. There seems to be adequate evidence of efficacy and short-term safety of metformin in relation to maternal and neonatal outcomes in GDM, with possible benefits related to lower maternal weight gain and lower risk of neonatal hypoglycemia and macrosomia. Additionally, metformin offers the advantages of oral administration, convenience, less cost and greater acceptability. Metformin may, therefore, be considered in milder forms of GDM where glycemic goals are not attained by lifestyle modification. However, failure rate is likely to be higher in those with an earlier diagnosis of GDM, higher blood glucose, higher body mass index (BMI) or previous history of GDM, and insulin remains the cornerstone of pharmacological treatment in such cases. The use of metformin in type 2 diabetes has been assessed in observational and small randomized trials. Metformin monotherapy in women with overt diabetes is highly unlikely to achieve glycemic targets. Hence, the use should be restricted as adjunct to insulin and may be considered in women with high insulin dose requirements or rapid weight gain. There is clearly a need for more clinical trials to assess the effect of combined insulin plus metformin therapy in pregnancy with type 2 diabetes. Additionally, there is a paucity of data on long-term effects in offspring exposed to metformin in utero. It is imperative to further explore its impact on offspring as metformin has significant transplacental transfer and has the potential to impact the programming of the epigenome. Therefore, caution must be exercised when prescribing metformin in pregnant women. More research is clearly needed before metformin can be considered as standard of care in the management of diabetes during pregnancy.

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“…In the last few years, two stereoisomers of inositol, myo-inositol (MI) and D-chiro-inositol (DCI) have attracted scientific interest and related research on them has gained momentum. MI and DCI are cyclic polyols (C 6 H 12 O 6 ) with MW 180.16, present in all living forms; they are involved in a wide array of metabolic pathways with significant therapeutic applications in pathologies (e.g., PCOS, GDM, MetSyn) where insulin sensitizing agents play a key role [ 4 , 6 , 7 ]. Obviously, they are even more useful as they do not involve significantly adverse events [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women

et al. 2018

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BackgroundMyo-inositol (MI), successfully used in polycystic ovary syndrome (PCOS), was administered with α-LA to exploit its action of favouring the passage of other molecules through biological barriers, and also considering its anti-inflammatory effect.MethodsPCOS patients, according to the Rotterdam ESHRE–ASRM criteria, with anovulation and infertility > 1 year, were included in this open and prospective study. The preliminary phase was aimed at determining a set of MI-resistant PCOS patients. This treatment involved 2 g MI, taken twice per day by oral route, for three months. The Homeostasis Model Assessment (HOMA) index and MI plasma levels were measured. In the main phase, previously selected MI-resistant patients received the same daily amount of MI plus 50 mg α-LA twice a day, for a further three months. Ovulation was assessed using ultrasound examination on days 12, 14 and 20 of the cycle. The HOMA index, lipid, hormone and MI plasma levels were detected at baseline and at the end of this phase.ResultsThirty-seven anovulatory PCOS subjects were included in the study. Following MI treatment, 23 of the 37 women (62%) ovulated, while 14 (38%) were resistant and did not ovulate. In the latter group, MI plasma levels did not increase. These MI-resistant patients underwent treatment in the main phase of the study, receiving MI and α-LA. After this combined treatment, 12 (86%) of them ovulated. Their MI plasma levels were found to be significantly higher than at baseline; also, a hormone and lipid profile improvement was recorded.ConclusionThe combination of MI with α-LA allowed us to obtain significant progress in the treatment of PCOS MI-resistant patients. Therefore, this new formulation was able to re-establish ovulation, greatly increasing the chances of desired pregnancy.Trial RegistrationClinical trial registration number: NCT03422289 (ClinicalTrials.gov registry).

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The Role of Metformin in Metabolic Disturbances during Pregnancy: Polycystic Ovary Syndrome and Gestational Diabetes Mellitus

Cited by 18 publications

References 166 publications

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

Metformin in the management of diabetes during pregnancy and lactation

Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women

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