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Lipids in polycystic ovary syndrome: Role of hyperinsulinemia and effects of metformin

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Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathes, affecting approximately 4% to 7% of women of reproductive age hirsutism, menstrual irregularities, and infertility, hyperandrogenemia, elevated luteinizing hormone (LH), and normal or decreased folliclestimulating hormone (FSH). 6/14/12

PCOS is characterized by insulin resistance and compensatory hyperinsulinemia. Dyslipidemia in PCOS is prevalent and characterized by elevated plasma levels of cholesterol, lowdensity lipoproteins (LDL), very-lowdensity lipoproteins (VLDL), and triglycerides, with concomitantly reduced concentration of high6/14/12

Women with a history of PCOS have increased systolic blood pressure and increased thickness of arterial intimamedia. Longterm complications of PCOS include increased risk of type 2 diabetes mellitus, atherosclerosis, coronary artery disease, and myocardial infarction
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Metformin use in PCOS led to an increase in insulin sensitivity accompanied by decreased insulin and androgen levels and frequently resulted in restoration of menstrual function.

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Material and methods

Women with PCOS were identified on the basis of Oligo or amenorrhea in conjunction with hyperandrogenism (acne, hirsutism) and/or hyperandrogenemia (serum total testosterone > 0.8 ng/mL) excluded: androgen secreting tumors, congenital adrenal hyperplasia (tested by evaluation of 17-hydroxyprogesterone), 6/14/12

The subjects were not engaged in intensive aerobic exercise and did not take medications which may affect lipid profile, carbohydrate metabolism, or reproductive functions, such as oral contraceptive pills for at least 2 months before the study
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88 women with PCOS hyperinsulinemic group on the basis of a fasting insulin >17 mU/mL. Women with hyperinsulinemia (n = 43) received metformin (500 mg po tid). After 3 months and again after 6 months of therapy, evaluations were repeated
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insulin was determined by enzymelinked immunosorbent assay (ELISA) Testosterone, LH, FSH, and prolactin were measured with specific chemiluminescence assays

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Levels of total cholesterol and triglycerides were determined using enzymatic colorimetric assays. HDL was separated by precipitating apolipoprotein-B. LDL was calculated using the Friedwald formula. Plasma glucose was determined by a chemiluminescence assay

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Comparison of the means was performed using the paired or nonpaired t test, as appropriate. In the absence of normality, nonparametric testing was performed.

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Result

The study evaluated 88 women diagnosed with PCOS; 43 of these women were hyperinsulinemic (fasting insulin>17 U/mL) and 45 were normoinsulinemic (fasting insulin <17 U/mL).

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All hyperinsulinemic women received metformin; 7 subjects experienced nausea during the first 2 weeks of treatment but did not discontinue the medication. After 3 months of metformin, 41 subjects were evaluated; the remaining 2 subjects were pregnant. After 6 months, 24 subjects were 6/14/12 evaluated; the remaining subjects

Hyperinsulinemic women had significantly lower HDL (by 11%), higher total cholesterol to HDL ratio (by 23%), and greater triglycerides (by 57%) than the normoinsulinemic group

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Hyperinsulinemic women received metformin and subsequently experienced an improvement of lipid profile at 3 months of therapy. Total cholesterol declined by 6%, LDL by 9%, and triglycerides by 17%.

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Continuation of metformin for additional 3 months resulted in further improvement of lipid profile: when compared with the pretreatment levels, total cholesterol declined by 11%, LDL by 12%, and triglycerides by 33%.

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Weight loss on metformin was observed in 33% of subjects. After metformin treatment a significant decline of fasting insulin was observed in both groups of subjects: those who did not lose weight and those who lost weight. Total cholesterol declined significantly among those who did not lose and among those who lost 6/14/12

when accounting for change of BMI, change of the total cholesterol was the greatest in women with the highest baseline cholesterol and the highest IGF-I. The greatest improvement of triglycerides was noted in women with the highest baseline triglycerides
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Comment

1) hyperinsulinemic subjects have a less favorable lipid profile than normoinsulinemic subjects; 2) use of metformin in treatment of hyperinsulinemic subjects results in a progressive improvement of lipid profile to the levels comparable to those found in normoinsulinemic women; and 3) the effect of metformin on lipid

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metformin reduced cholesterol but not triglycerides. Recent studies of metformin use in women with PCOS have demonstrated an improvement of HDL but no significant effect on total cholesterol or triglycerides. In the present study, metformin use was effective in reducing total cholesterol, LDL and, especially, triglycerides. The divergence of the 6/14/12

The lipid profile in the hyperinsulinemic group was significantly worse than in the normoinsulinemic group

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Metformin has been shown to improve menstrual regularity, ameliorate hirsutism, and be useful as a primary or adjuvant therapy of infertility However, the role of metformin in protection from longterm cardiovascular complications of PCOS is unclear.
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the use of metformin is associated with a decline in insulin levels and a decrease of BMI.

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It should be noted that this study represents a prospective evaluation of a cohort and evaluates only hyperinsulinemic subjects using a single dose of metformin. Ideally, further studies would involve subject randomization, testing of broader populations of women with PCOS, and identification of optimal doses of metformin. Such studies 6/14/12

In conclusion, use of metformin in hyperinsulinemic women with PCOS is associated with a significantimprovement of lipid profile; these findings support the notion that metformin use may be considered as prophylactic therapy aimed at lowering cardiovascular risk factors. 6/14/12

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6/14/12

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