Lipids in Polycystic Ovary Syndrome

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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Lipids in Polycystic Ovary Syndrome