7/31/2019 Lipids in Polycystic Ovary Syndrome
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Lipids in polycystic ovarysyndrome: Role of
hyperinsulinemia andeffects of metformin
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Polycystic ovary syndrome (PCOS) isone of the most commonendocrinopathes, affecting
approximately 4% to 7% of women ofreproductive age
hirsutism, menstrual irregularities,
and infertility, hyperandrogenemia,elevated luteinizing hormone (LH),and normal or decreased follicle-
stimulating hormone (FSH).
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PCOS is characterized by insulinresistance and compensatoryhyperinsulinemia.
Dyslipidemia in PCOS is prevalentand characterized by elevatedplasma levels of cholesterol, low-
density lipoproteins (LDL), very-low-density lipoproteins (VLDL), andtriglycerides, with concomitantly
reduced concentration of high-
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Women with a history of PCOS haveincreased systolic blood pressure andincreased thickness of arterial intima-
media. Longterm complications ofPCOS include increased risk of type 2diabetes mellitus, atherosclerosis,
coronary artery disease, andmyocardial infarction
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Metformin use in PCOS led to anincrease in insulin sensitivityaccompanied by decreased insulin
and androgen levels and frequentlyresulted in restoration of menstrualfunction.
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Material and methods
Women with PCOS were identified onthe basis of Oligo or amenorrhea inconjunction with hyperandrogenism
(acne, hirsutism) and/orhyperandrogenemia (serum totaltestosterone > 0.8 ng/mL)
excluded: androgen secretingtumors, congenital adrenalhyperplasia (tested by evaluation of
17-hydroxyprogesterone),
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The subjects were not engaged inintensive aerobic exercise and didnot take medications which may
affect lipid profile, carbohydratemetabolism, or reproductivefunctions, such as oral contraceptive
pills for at least 2 months before thestudy
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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 potid).
After 3 months and again after 6months of therapy, evaluations wererepeated
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insulin was determined by enzyme-linked immunosorbent assay (ELISA)
Testosterone, LH, FSH, and prolactinwere measured with specificchemiluminescence assays
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Levels of total cholesterol andtriglycerides were determined usingenzymatic colorimetric assays.
HDL was separated by precipitatingapolipoprotein-B.
LDL was calculated using theFriedwald formula.
Plasma glucose was determined by a
chemiluminescence assay
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Comparison of the means wasperformed using the paired ornonpaired t test, as appropriate. In
the absence of normality,nonparametric testing wasperformed.
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Result
The study evaluated 88 womendiagnosed with PCOS; 43 of thesewomen were hyperinsulinemic
(fasting insulin>17 U/mL) and 45were normoinsulinemic (fastinginsulin
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All hyperinsulinemic women receivedmetformin; 7 subjects experiencednausea during the first 2 weeks of
treatment but did not discontinue themedication.
After 3 months of metformin, 41
subjects were evaluated; theremaining 2 subjects were pregnant.
After 6 months, 24 subjects were
evaluated; the remaining subjects
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Hyperinsulinemic women hadsignificantly lower HDL (by 11%),higher total cholesterol to HDL ratio
(by 23%), and greater triglycerides(by 57%) than the normoinsulinemicgroup
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Hyperinsulinemic women receivedmetformin and subsequentlyexperienced an improvement of lipid
profile at 3 months of therapy. Totalcholesterol declined by 6%, LDL by9%, and triglycerides by 17%.
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Continuation of metformin foradditional 3 months resulted infurther improvement of lipid profile:
when compared with thepretreatment levels, total cholesteroldeclined by 11%, LDL by 12%, and
triglycerides by 33%.
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Weight loss on metformin wasobserved in 33% of subjects. Aftermetformin treatment a significant
decline of fasting insulin wasobserved 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
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when accounting for change of BMI,change of the total cholesterol wasthe greatest in women with the
highest baseline cholesterol and thehighest IGF-I.
The greatest improvement of
triglycerides was noted in womenwith the highest baselinetriglycerides
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Comment
1) hyperinsulinemic subjects have aless favorable lipid profile thannormoinsulinemic subjects;
2) use of metformin in treatment ofhyperinsulinemic subjects results in aprogressive improvement of lipid
profile to the levels comparable tothose found in normoinsulinemicwomen; and
3) the effect of metformin on lipid
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metformin reduced cholesterol butnot triglycerides. Recent studies ofmetformin use in women with PCOS
have demonstrated an improvementof HDL but no significant effect ontotal cholesterol or triglycerides.
In the present study, metformin usewas effective in reducing totalcholesterol, LDL and, especially,
triglycerides. The divergence of the
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The lipid profile in thehyperinsulinemic group wassignificantly worse than in the
normoinsulinemic group
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Metformin has been shown toimprove menstrual regularity,ameliorate hirsutism, and be useful
as a primary or adjuvant therapy ofinfertility However, the role ofmetformin in protection from long-
term cardiovascular complications ofPCOS is unclear.
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the use of metformin is associatedwith a decline in insulin levels and adecrease of BMI.
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It should be noted that this studyrepresents a prospective evaluationof a cohort and evaluates only
hyperinsulinemic subjects using asingle dose of metformin.
Ideally, further studies would involve
subject randomization, testing ofbroader populations of women withPCOS, and identification of optimal
doses of metformin. Such studies
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In conclusion, use of metformin inhyperinsulinemic women with PCOSis associated with a
significantimprovement of lipidprofile;
these findings support the notion
that metformin use may beconsidered as prophylactic therapyaimed at lowering cardiovascular risk
factors.
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