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CHRONICLES IN CHOLESTEROLAn Insiders Guide to State of The Art Cardiovascular

Prevention Laboratory Testing Available From

Everest Clinical Laboratories

Polycystic ovarian syndrome (PCOS) is a highlyprevalent disease affecting approximately 10% ofreproductive-age women. The hallmark of PCOS isandrogen excess which is driven by an underlyinginsulin-resistant state. Patients with PCOS have ahigh prevalence of the metabolic syndrome and as aresult are at increased risk for type II diabetes as wellas increased risk for cardiovascular disease. Impairedglucose tolerance or overt type II diabetes develops

by the age of 30 in 30

50 % of obese women with PCOS

PCOS is a clinical diagnosis associated with chronicanovulation and clinical or biochemical signs ofhyperandrogenism. Some patients do not manifestovarian cysts. The complications of PCOS includeinfertility, menstrual dysfunction, hirsutism, acne andobesity.

In addition to the lipid abnormalities seen in PCOSpatients, these patients often have increasedhsCRP, increased PAI-1 and hyperhomocysteinemialevels. Structural vascular abnormalities includeincreased carotid intimal medial thickness (CIMT),endothelial dysfunction and increased coronarycalcium scores.

Young, obese women with PCOS have a highprevalence of early asymptomatic coronaryatherosclerosis compared to obese controls.Patients with PCOS have a high prevalence of themetabolic syndrome and as a result are at increasedrisk for type II diabetes as well as increased risk forcardiovascular disease. The lipid abnormalities inPCOS patients are similar to metabolic syndromepatients and type II diabetics: low HDL-C (150 mg/dL), and increased small dense LDL particleconcentration. The low HDL- C is independent of bodyweight.

February, 2013 VOL 4 ISSUE 1

In This Issue: Polycystic OvarianSyndrome and Lipids

PCOS patients are at high risk for

cardiovascular disease, even at

young age.

Most manifest the lipid

abnormalities of seen in insulin

resistance.

Lipid abnormalities such as high

triglycerides, low HDL-C, and

increased LDL-P or Apo B, all easily

evaluated in many patients by

looking first for an elevated non-

HDL-C.

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A debate arises as to where to focus treatment withregards to PCOS patients. Some clinician focus on anti-androgenizing therapies with agents such asspironolactone. This strategy does not always mitigate theinsulin resistance and lipid abnormalities of the PCOSpatient or reduce their vast cardiovascular risk.

Treatment with oral contraceptives has been anothertraditional approach that helps correct the reproductive andmenstrual abnormalities thus providing symptom relief.Unfortunately, such hormonal therapy may be associatedwith adverse metabolic consequences such as decreasedinsulin sensitivity, impaired glucose tolerance, increasedtriglycerides, and increased risk of thrombosis.

Since insulin resistance is at the core of the cardiovascularpathophysiology of this disorder, it would seem prudent toaddress this problem. Excess insulin leads to decreasedsex hormone binding globulin (SHBG) synthesis in the liverand therefore increased levels of circulating freetestosterone. It is this pathway that creates the androgenexcess.

The initial treatment of PCOS should be aimed at weightloss. Even a small reduction of body weight by 25 % canrestore ovulation, lower insulin levels, increase insulinsensitivity, increase SHBG and reduce testosterone levelsand acne. LDL-C and LDL-P will generally improve with theweight loss.

In addition to lifestyle changes, metformin orthiazolidinediones (TZDs) can be used as insulinsensitizers and to correct insulin resistance. Metformin is acategory B drug in pregnancy, so it can be used fairlysafely in young women. Metformin also effectively reduces

plasma insulin levels and reduces LDL-C. Metformin alsodramatically lowers LDL-P.

Although TZDs have fallen into some disfavor recently, allthe TZDs have shown benefit in the treatment of themetabolic abnormalities of PCOS. TZDs have also all beenshown to decrease androgen levels, improve ovulation, andreduce progression to overt type II DM in patients withPCOS and IGT. Lipids profiles also improve with TZDs,although effects vary by specific TZD. Pioglitazone is morelikely to produces a drop in triglycerides and an increase inHDL-C, whereas all TZDs shift LDL particles to largebuoyant particles. These lipid modifying differences by theTZDs may be explained by their variable effect on thePPAR-alpha transcription promoter. TZDs may however

cause weight gain. TZDs are considered category C drugsin pregnancy

By Spencer Kroll MD PhD

National Lipid Association Board Certified

Board of Directors, Northeast Lipid Association

February, 2013 VOL 4 ISSUE 1

Patients with PCOS will benefit from

cardiovascular prevention efforts.

Therapeutic lifestyle changes and/or

pharmacotherapy should be initiated

even at an early age