Metformin during pregnancy in polycystic ovary syndrome: another vitamin bites the dust.
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ABSTRACT:
SUBMITTER: Legro RS
PROVIDER: S-EPMC2999976 | biostudies-literature | 2010 Dec
REPOSITORIES: biostudies-literature
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Metformin during pregnancy in polycystic ovary syndrome: another vitamin bites the dust.
The Journal of clinical endocrinology and metabolism 20101201 12
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Project description:ObjectivePolycystic ovary syndrome (PCOS) and hypothyroidism are related conditions, and both are associated with adverse pregnancy outcomes. Knowledge is lacking about the complex interaction between thyroid status and PCOS during pregnancy. We investigated the thyroid status and its association with pregnancy complications in PCOS, and in relation to metformin treatment.DesignPost-hoc analyses of two randomized, double-blind, placebo-controlled trials.Methods288 pregnant women with PCOS were randomized to treatment with metformin or placebo from first trimester to delivery. We measured serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) at gestational week (gw) 5-12, 19, 32 and 36 and related to metformin treatment and pregnancy complications. Thyroid peroxidase antibodies (TPO-ab) were analyzed at inclusion and at gw 36.ResultsThe overall prevalence of subclinical and overt hypothyroidism was 1.5% and 0%, respectively. The TSH level was not affected by metformin, whereas fT4 was significantly higher in the metformin group with less decrease throughout pregnancy compared to placebo, p<0.001. A lower decrease in fT4 during pregnancy correlated to less weight gain (r= -0.17, p=0.020) and tended to be associated with reduced odds ratio for gestational diabetes (OR 0.85 per 1 pmol/L, 95% CI 0.71;1.02).ConclusionsIn women with PCOS, metformin treatment during pregnancy was associated with less decrease in fT4 compared to placebo, while it did not affect TSH. A smaller decrease in fT4 correlated to less weight gain and tended to be associated with a lower risk of gestational diabetes.Clinical trial registrationClinicalTrials.gov, identifier NCT00159536 (The PregMet study); identifier NCT03259919 (The pilot study).
| S-EPMC8898827 | biostudies-literature
Project description:Maintenance of gestation implicates complex function of multiple endocrine mechanisms, and disruptions of the global metabolic environment prompt profound consequences on fetomaternal well-being during pregnancy and postpartum. Polycystic Ovary Syndrome (PCOS) and gestational diabetes mellitus (GDM) are very frequent conditions which increase risk for pregnancy complications, including early pregnancy loss, pregnancy-induced hypertensive disorders, and preterm labor, among many others. Insulin resistance (IR) plays a pivotal role in the pathogenesis of both PCOS and GDM, representing an important therapeutic target, with metformin being the most widely prescribed insulin-sensitizing antidiabetic drug. Although traditional views neglect use of oral antidiabetic agents during pregnancy, increasing evidence of safety during gestation has led to metformin now being recognized as a valuable tool in prevention of IR-related pregnancy complications and management of GDM. Metformin has been demonstrated to reduce rates of early pregnancy loss and onset of GDM in women with PCOS, and it appears to offer better metabolic control than insulin and other oral antidiabetic drugs during pregnancy. This review aims to summarize key aspects of current evidence concerning molecular and epidemiological knowledge on metformin use during pregnancy in the setting of PCOS and GDM.
| S-EPMC4334060 | biostudies-other
Project description:Background and objectivesMetformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy-related changes in metformin pharmacokinetics and the return to the non-pregnant state.MethodA subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time-points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four-parameter logistic model.FindingsThe mean steady-state serum concentration of metformin during pregnancy was 9.39 μmoL/L, whereas the post partum concentration was 12.36 μmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum.ConclusionClinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.
| S-EPMC9304251 | biostudies-literature
Project description:BackgroundPolycystic Ovary Syndrome (PCOS) is an endocrine disorder that affects women in reproductive age and represents an unfavourable risk factor for several pregnancy and perinatal outcomes. Despite, no guidelines or pharmaceutical strategies for treating PCOS during pregnancy are available. The aim of this study is to determine the association between polycystic ovary syndrome with or without metformin and the pregnancy, perinatal outcomes as well as the risk of obesity in children born to these mothers.MethodsIn this nationwide population-based cohort study based in Swedish population, all singleton births (n = 1,016,805) from 686,847 women since 2006 up to 2016 were included. Multivariable logistic and Cox regression modelling with odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals were used to study the association between the exposure of maternal PCOS, metformin during pregnancy (or the combination of both) and: 1) Pregnancy outcomes: preeclampsia, gestational diabetes, caesarean section, and acute caesarean section, 2) Perinatal outcomes: preterm birth, stillbirth, low birth weight, macrosomia, Apgar < 7 at 5 min, small for gestational age and large for gestational age, and 3) Childhood Obesity.ResultsPCOS in women without metformin use during pregnancy was associated with higher risks of preeclampsia (OR = 1.09, 1.02-1.17), gestational diabetes (OR = 1.71, 1.53-1.91) and caesarean section (OR = 1.08, 1.04-1.12), preterm birth (OR = 1.30, 1.23-1.38), low birth weight (OR = 1.29, 1.20-1.38), low Apgar scores (OR = 1.17, 1.05-1.31) and large for gestational age (OR = 1.11, 1.03-1.20). Metformin use during pregnancy (in women without PCOS) was associated with a 29% lower risks of preeclampsia (OR = 0.71, 0.51-0.97), macrosomia and large for gestational age. Obesity was more common among children born to mothers with PCOS without metformin (HR = 1.61, 1.44-1.81); and those with metformin without PCOS (HR = 1.67, 1.05-2.65). PCOS with metformin was not associated with any adverse outcome.ConclusionPCOS was associated with increased risks of adverse pregnancy and perinatal outcomes and childhood obesity. Metformin appears to reduce these risks in mothers with polycystic ovary syndrome and their children; but may increase the risk of childhood-obesity in children form women without PCOS.
| S-EPMC8819934 | biostudies-literature
Project description:Unspent Transaction Outputs (UTXOs) are the internal mechanism used in many cryptocurrencies to represent coins. Such representation has some clear benefits, but also entails some complexities that, if not properly handled, may leave the system in an inefficient state. Specifically, inefficiencies arise when wallets (the software responsible for transferring coins between parties) do not manage UTXOs properly when performing payments. In this paper, we study three cryptocurrencies: Bitcoin, Bitcoin Cash and Litecoin, by analysing the state of their UTXO sets, that is, the status of their sets of spendable coins. These three cryptocurrencies are the top-3 UTXO-based cryptocurrencies by market capitalization. Our analysis shows that the usage of each cryptocurrency presents some differences, and led to different results. Furthermore, it also points out that the management of the transactions has not always been performed efficiently and therefore, the current state of the UTXO sets is far from ideal.
| S-EPMC6366196 | biostudies-literature
Project description: Not available
| S-EPMC8171384 | biostudies-literature
Project description:ContextPolycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The selection of first-line therapies for ovulation induction is empiric.ObjectiveThe aim of the study was to develop a clinically useful predictive model of live birth with varying ovulation induction methods.Design, setting, and participantsWe built four prognostic models from a large multicenter randomized controlled infertility trial of 626 women with PCOS performed at academic health centers in the United States to predict success of ovulation, conception, pregnancy, and live birth, evaluating the influence of patients' baseline characteristics.InterventionsOvulation was induced with clomiphene, metformin, or the combination of both for up to six cycles or conception.Main outcome measureThe primary outcome of the trial was the rate of live births.ResultsBaseline free androgen index, baseline proinsulin level, interaction of treatment arm with body mass index, and duration of attempting conception were significant predictors in all four models. History of a prior loss predicted ovulation and conception, but not pregnancy or live birth. A modified Ferriman Gallwey hirsutism score of less than 8 was predictive of conception, pregnancy, and live birth (although it did not predict ovulation success). Age was a divergent predictor based on outcome; age greater than 34 predicted ovulation, whereas age less than 35 was a predictive factor for a successful pregnancy and live birth. Smoking history had no predictive value.ConclusionsA live birth prediction chart developed from basic clinical parameters (body mass index, age, hirsutism score, and duration of attempting conception) may help physicians counsel and select infertility treatments for women with PCOS.
| S-EPMC2741722 | biostudies-literature
Project description:Background and objectivePCOS is a common metabolic disorder in women of reproductive age, which pathogenesis is very complex. The role of ferroptosis in PCOS is a novel finding, and the mechanistic studies are not clear. Metformin is a commonly used drug of PCOS but few studies on whether metformin can improve the follicle development and ovarian function in PCOS. We aims to use PCOS mouse model to study the effect of metformin on PCOS based on the ovarian function and explored the regulation of metformin in PCOS mice by intervening in ferroptosis pathway.Materials and methodsC57 BL/6J female mice aged 4-5 weeks were purchased and gavaged with letrozole (1 mg/kg/day) combined with high-fat diet for 21days to establish PCOS model, and control group was set up. After modeling, the mice were divided into PCOS model group and metformin treatment group (Met) (n=6).The Met group were gavaged metformin (200 mg/kg/day) for 28 days. The body weight, estrous cycle, glucose tolerance test (OGTT)and insulin resistance test (ITT) were monitored. Then, The mice were euthanized to collect serum and ovaries. Elisa was used to detect changes in related serum hormones (E2, LH, FSH, TP). Ovaries used for molecular biology experiments to detect changes in GPX4, SIRT3, AMPK/p-AMPK, and mTOR/p-mTOR by Western blot and qPCR.ResultsCompared with the model group mice, body weight was significantly reduced, and their estrous cycle was restored in Met group. The results of OGTT and ITT showed an improvment of glucose tolerance and insulin resistance. Morphological results showed that after metformin treatment, polycystic lesions in ovaries were reduced, the ovarian function was restored, and the expressions of SIRT3 and GPX4 were elevated. WB results demonstrated that the expressions of p-mTOR and p-AMPK in ovaries were significantly reduced in Model group, but reversed in MET group.ConclusionOur study confirmed metformin could not only improve body weight and metabolism disorders, but also improve ovarian dysfunction in PCOS mice.In addition, we explored metformin could regulate ferroptosis to improve PCOS via the SIRT3/AMPK/mTOR pathway. Our study complements the mechanisms by which metformin improves PCOS.
| S-EPMC9900736 | biostudies-literature
Project description:ObjectiveTo investigate the factors that are associated with the effect of metformin on endothelial dysfunction in polycystic ovary syndrome (PCOS).Patients and methodsFrom March 24, 2014, to November 18, 2016, 48 women with PCOS were randomly assigned to 1500 mg/d of metformin (N=29) or no treatment (N=13) for 3 months; 42 patients (29 in the initial treatment group and 13 in the no treatment group) completed the study. Study variables were measured at baseline and after 3 months. Participants who did not receive metformin initially were then treated with metformin for another 3 months, and study variables were measured again. Endothelial function was measured as reactive hyperemia-peripheral arterial tonometry (RH-PAT) from the index finger.ResultsThe age and baseline endothelial function (mean ± SD) of the participants were 32.7±6.9 years and 1.8±0.5, respectively. No notable change was observed in endothelial function after 3 months with metformin compared with no treatment. However, after stratifying participants who received metformin based on baseline endothelial function, there was a significant improvement following metformin treatment in participants with abnormal baseline endothelial function (1.3±0.3 vs 1.7±0.3; P<.001) but not in those with normal baseline endothelial function (2.1±0.4 vs 2.0±0.5; P=.11).ConclusionMetformin improves endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism, dyslipidemia, or presence of prediabetes. Metformin has a direct effect on endothelial function in PCOS, and measurement of endothelial function can stratify and follow response to metformin treatment in PCOS.Trial registrationclinicaltrials.gov Identifier: NCT02086526.
| S-EPMC8050832 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. This study was designed to investigate the associations of vitamin D receptor (VDR) gene variants with PCOS risk and the severity of the disease phenotype among Egyptian women.MethodsIn this study, 185 women with PCOS and 207 fertile women as controls were recruited. Cases were divided into phenotype groups based on their clinical and paraclinical features. Clinical and laboratory data were measured in the patient and control groups. All individuals were genotyped for nine single-nucleotide polymorphisms (SNPs) located across the VDR gene using TaqMan allelic discrimination real-time polymerase chain reaction.ResultsWomen with PCOS were significantly (P ≤ 0.001) higher body mass index (BMI) (22.77 ± 2.5) than controls (21.68 ± 1.85 kg/m2). Women with PCOS had significantly higher anti-Mullerian hormone, prolactin, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate levels than the control group (P ≤ 0.001). The level of FSH was significantly lower in women with PCOS than in the control group (P ≤ 0.001). Analysis of the VDR rs4516035, rs2107301, rs1544410 (BsmI), and rs731236 (TaqI) SNPs showed a significant association with PCOS phenotype A. Furthermore, rs2228570 (FokI), rs3782905, rs7975232 (ApaI), and rs739837 SNPs showed a significant association with PCOS phenotype C. Furthermore, rs11568820 SNP showed a significant association with PCOS phenotype D (P < 0.05).ConclusionsThe findings of this study indicate that variations in the VDR gene were associated with an increased risk of PCOS in Egyptian women.
| S-EPMC10197246 | biostudies-literature