The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome

Yılmaz, Murat; Bırı, Aydan; Karakoç, Ayhan; Törüner, Füsun Baloş; Bingöl, Banu; Çakır, Nuri; Tıraş, Bülent; Ayvaz, Göksün; Arslan, Metin

doi:10.1007/bf03345339

Cited by 70 publications

(51 citation statements)

References 42 publications

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“…This drug also reduces appetite in many PCOS women and is thus often [133], but not always [134], associated with more weight loss. Metformin has been shown to be effective in all women with PCOS, even those without insulin resistance and hyperinsulinemia [47, [135][136][137], but tends to be more effective in lean as compared to obese PCOS women [138]. The effects of metformin in PCOS are probably mainly mediated through a reduction in insulin levels, which is observed both in insulin-sensitive and insulin-resistant PCOS women because of the reduction in hepatic glucose production.…”

Section: Insulin-sensitizing Drugsmentioning

confidence: 99%

“…Several studies have demonstrated the therapeutic benefits of one or another TZD on insulin resistance, ovulatory dysfunction and hyperandrogenism in PCOS women [141][142][143][144]. Similar to metformin, TZDs were found to improve hyperandrogenism and ovulation rates even in lean women with PCOS [47,135] and with normal insulin levels [47]. TZDs seem at least as effective as metformin for clinical improvement of PCOS [2,122].…”

Section: Insulin-sensitizing Drugsmentioning

confidence: 99%

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Insulin and hyperandrogenism in women with polycystic ovary syndrome

Baptiste

Battista

Trottier

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

261

199

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Polycystic ovary syndrome (PCOS) is a very common endocrine disorder characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and/or polycystic ovaries. But most experts consider that hyperandrogenism is the main characteristic of PCOS. Several theories propose different mechanisms to explain PCOS manifestations: (1) a primary enzymatic default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in gonadotropin releasing hormone (GnRH) secretion that promotes luteal hormone (LH) secretion; or (3) alterations in insulin actions that lead to insulin resistance with compensatory hyperinsulinemia. However, in the past 20 years there has been growing evidence supporting that defects in insulin actions or in the insulin signalling pathways are central in the pathogenesis of the syndrome. Indeed, most women with PCOS are metabolically insulin resistant, in part due to genetic predisposition and in part secondary to obesity. But some women with typical PCOS do not display insulin resistance, which supports the hypothesis of a genetic predisposition specific to PCOS that would be revealed by the development of insulin resistance and compensatory hyperinsulinemia in most, but not all, women with PCOS. However, these hypotheses are not yet appropriately confirmed, and more research is still needed to unravel the true pathogenesis underlying this syndrome. The present review thus aims at discussing new concepts and findings regarding insulin actions in PCOS women and how it is related to hyperandrogenemia.

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Section: Insulin-sensitizing Drugsmentioning

confidence: 99%

Section: Insulin-sensitizing Drugsmentioning

confidence: 99%

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Baptiste

Battista

Trottier

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

261

199

View full text Add to dashboard Cite

show abstract

“…We chose a 130 -200 nmol/l or 950-1500 ng/ml range as a two-to threefold elevated physiological range indicative of mild insulin resistance. Since that time, several papers have been published showing this two-to threefold elevation in fasting serum insulin levels and in IGF-I levels among PCOS patients (29,30). This study assumes that serum and tubal IGF-I levels are similar.…”

Section: Resultsmentioning

confidence: 97%

AMP Kinase Activation Increases Glucose Uptake, Decreases Apoptosis, and Improves Pregnancy Outcome in Embryos Exposed to High IGF-I Concentrations

et al. 2007

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Women with polycystic ovarian syndrome are at increased risk of miscarriage. Although evidence exists that metformin reduces this risk, the mechanism is unknown. This study tests the hypothesis that AMP kinase (AMPK) activation with metformin directly improves insulin signaling within the blastocyst, leading to improved pregnancy outcomes. Murine embryos were exposed to 200 nmol/l IGF-I, similar to the concentrations that can occur during polycystic ovary syndrome (PCOS). Resulting blastocysts were compared with embryos cocultured with excess IGF-I plus metformin and embryos cultured in control medium for the following: AMPK phosphorylation, insulin-stimulated glucose uptake, and apoptosis. Study and control blastocysts were also transferred into control animals. On embryonic day (E) 14.5, resulting fetuses were examined for size and rates of fetal implantation and resorption. Compared with control blastocysts, blastocysts exposed to high concentrations of IGF-I showed a decrease in AMPK activation and insulin-stimulated glucose uptake and an increase in the number of apoptotic nuclei. Blastocysts cocultured in metformin and excess IGF-I performed as well as controls in all studies. 5-Aminoimidazole-4-carboxamide 1-␤-D-ribofuranoside, another AMPK activator, also prevented the effects of excess IGF-I on blastocysts. Implantation rates and fetal size at day 14.5 were significantly lower among IGF-I-exposed embryos transferred into control mothers compared with control embryos transferred into control mothers. Both of these parameters were reversed by coincubation with metformin and IGF-I before transfer. Activation of embryonic AMPK may be the mechanism responsible for the improved pregnancy outcomes seen in PCOS patients taking metformin. Diabetes 56:2228-2234, 2007 W omen with polycystic ovary syndrome (PCOS) experience oligomenorrhea/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovaries (1). The clinical presentation is variable, but many women with PCOS also exhibit obesity, hyperinsulinemia with insulin resistance, and infertility with recurrent pregnancy loss (2-4). The etiology of this recurrent pregnancy loss remains unclear. Both high concentrations of androgens and gonadotropins have been suggested, but only small, correlative clinical investigations have been conducted (5,6). Bioactive levels of the insulin-like growth factor, IGF-I, are also increased in PCOS patients because of an insulininduced decrease in the production of IGF binding protein-1 (IGFBP-1) (7,8).The preimplantation blastocyst stage embryo is an insulin-sensitive tissue (9,10). Prior studies have shown that the murine blastocyst responds to insulin or IGF-I by increasing glucose uptake and that this event occurs via the IGF-I receptor. IGF-I receptor signaling induces translocation of GLUT8 to the plasma membrane of the trophectoderm cells of the embryo (11). Expression of GLUT8 and translocation to the plasma membrane are critical for embryo survival (12,13). On exposure to high concentration of IGF-I or insul...

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“…Several studies have revealed that metfolmin, insulin-sensitizer, treatment for nonobese PCOS improved the metabolic characteristics involving HOMA-R, fasting glucose and insulin levels, area under the curve of insulin response in addition to hyperandrogenism, menstrual irregularities [22][23][24], and pregnancy rate [25].…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance in nonobese Japanese women with polycystic ovary syndrome is associated with poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response

Negishi

Nakao²,

Kimura

et al. 2015

Reprod Medicine & Biology

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Purpose To determine the prevalence of insulin resistance (IR) and impaired glucose tolerance (IGT) in PCOS patients, the optimal screening method, and to compare our findings between nonobese and obese Japanese women with PCOS. Methods Ninety-eight PCOS patients were included in this research from 2006 to 2013. Glucose tolerance test (OGTT) was performed. Serum glucose and insulin concentration were assayed before and 30, 60, and 120 min after taking 75 g of glucose.Results All examined metabolic parameters were significantly favorable in the nonobese subjects, below 25 kg/m 2 . HOMA-IR, fasting insulin, glucose 120 , and insulin 120 showed strong correlations with BMI. A total of 1.4 % of nonobese women had IR based on fasting insulin or HOMA-IR. However, 15.5 % (11/71) of nonobese women had IR as determined by a continuous increase of serum insulin level in OGTT. In comparison, the prevalence of IR among the obese women ranged from 41 to 59 %. AUC glucose , glucose 60 , glucose 120 , and insulin 120 in nonobese women with a continuous insulin increase were higher than those without such a continuous increase.Conclusions All examined metabolic parameters were significantly correlated with BMI. As the presence of a continuous increase of insulin level reflects to some degree poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response compared with non-continuous insulin increase, OGTT might not been excluded to determine IR and IGT for nonobese women with PCOS.

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The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome

Cited by 70 publications

References 42 publications

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Insulin and hyperandrogenism in women with polycystic ovary syndrome

AMP Kinase Activation Increases Glucose Uptake, Decreases Apoptosis, and Improves Pregnancy Outcome in Embryos Exposed to High IGF-I Concentrations

Insulin resistance in nonobese Japanese women with polycystic ovary syndrome is associated with poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response

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