Polycystic ovary syndrome and the metabolic syndrome

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Polycystic ovary syndrome and the metabolic syndrome

JoAnn Guest

Mar 16, 2006 04:21 PST

 

Polycystic ovary syndrome and the metabolic syndrome

Clinical Diabetes, Fall, 2003 by Julie L. Sharpless

 

Diabetologists have long recognized the comorbid diseases of

obesity, hypertension, and hyperlipidemia in their type 2 diabetic

patients, and the necessity of treating these conditions in order to

improve outcomes.

 

 

Cardiovascular disease (CVD) is the number-one cause of death among

patients with diabetes, and its prevention is at the forefront of

modern diabetes care.

 

The clustering of insulin resistance, obesity,

hypertension, and dyslipidemia has been termed " the metabolic

syndrome. "

 

 

As national attention is focused on the emerging epidemic of type 2

diabetes and obesity, more energy is being directed toward earlier

detection, improved therapies, and potential prevention.

 

One condition commonly detected in a younger age group and

associated with a high risk

of progression to diabetes is polycystic ovary syndrome (PCOS).

 

Interestingly, many of the features of the metabolic syndrome,

including

insulin resistance, obesity, and dyslipidemias, are also present in

PCOS. Is PCOS an early manifestation of the metabolic syndrome?

 

Recent Developments Regarding the Metabolic Syndrome

 

The metabolic syndrome is composed of abnormalities that increase

cardiovascular risk. Although each constituent condition is

associated with heart disease in its own right, the combination of

these conditions far more powerfully augments cardiovascular risk.

 

The metabolic syndrome was recently codified in the National

Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-

III) guidelines, but has long been the subject of extensive research

and debate.

 

The NCEP definition includes fasting glucose, waist circumference,

blood

pressure, and lipid criteria pertaining to triglycerides and HDL

cholesterol.

 

(1) An earlier definition by the World Health Organization

(WHO) relied more heavily on insulin resistance as a necessary

component

of the metablic syndrome (2) and was thus closer to the original

description of the " insulin resistance syndrome " or " syndrome X "

within the diabetic population. (3) Definitions of the metabolic

syndrome are summarized in Table 1.

 

A major advantage of the NCEP definition is its ease of application.

For instance, while neither sensitive nor specific as an indicator

of insulin resistance, fasting glucose testing identifies further

developed abnormalities of glucose regulation and can readily be

performed in clinical practice and large clinical trials.

 

For the WHO definition,

measurement of insulin resistance requires a cumbersome clamp study,

which has confounded its use. Thus, major epidemiological studies

such as the European Group for the Study of Insulin Resistance and

the Botnia study in Finland and Sweden used widely applicable

surrogate markers of

insulin resistance, such as fasting glucose and insulin levels, (4)

or

glucose tolerance tests. (5) Additionally, newer data have allowed

subtle refinements in cut-off criteria based on outcomes research.

 

 

Just as the blood glucose level used to define diabetes was lowered

in 1997 based on outcomes,

(6) definitions of hypertension in the metabolic syndrome have

recently been lowered. (7)

 

Finally, waist circumference

has replaced BMI as a marker of obesity because of its better

correlation with intra-abdominal visceral adipose tissue and

worsened

cardiovascular outcomes. (

 

Using data from the Kuopio Finnish cohort, the NCEP ATP-III and the

WHO modified definitions of the metabolic syndrome were both

validated in a large epidemiological study that found up to fours

times higher coronary

heart disease (CHD) mortality in patients with the metabolic

syndrome.

(9)

 

The stated purposes of the NCEP ATP-III guidelines were to maintain

the original ATP-I and -II goal of primary prevention of CHD in

people with

high LDL cholesterol with the new focus on people with multiple risk

factors, such as those with the metabolic syndrome)

 

Women with PCOS are such a group.

---

 

What is PCOS?

 

PCOS is familiar to internists and diabetologists because of its

frequent occurrence as a precursor to diabetes. PCOS is clinically

defined as oligomenorrhea associated with hyperandrogenism. It has

been

described poetically as " the thief of womanhood " (10) because women

with

PCOS seek medical attention for infertility and hirsutism.

Characteristics of PCOS are summarized in Table 2.

 

That PCOS also conveys significant risks for diabetes and

endometrial cancer is a fact that has been clinically under-

recognized.

 

PCOS may also be associated with an increased risk for CVD; several

studies have

shown increased markers of CVD, usually in relation to features of

the metabolic syndrome. Many women with PCOS have additional

features of the

metabolic syndrome, especially insulin resistance and obesity.

 

Women with PCOS have a higher prevalence and a greater degree of

hyperinsulinemia (11,12) and insulin resistance (13-15) than

weight-matched control subjects.

 

Of women who have PCOS, as many as 30%

have impaired glucose tolerance (IGT) and an additional 7.5% have

diabetes. (16) Even among nonobese women with PCOS, 10.3% have IGT.

and

1.5% have diabetes.

 

(16) In long-term follow-up, 16% of women who had

been treated for PCOS 20-30 years earlier had developed diabetes by

the

age of menopause. (17) The etiology of the insulin resistance is

unclear, but suppression of the excess androgens does not alter the

insulin resistance. (18,19)

 

Insulin resistance is worsened by the coexistence of obesity, which

is

also increased in the PCOS population. (20) More than 40% of PCOS

patients are obese. (21,22)

 

The insulin resistance is disproportionate

to the obesity, however. Obese women with PCOS have greater insulin

resistance than weight-matched control subjects or lean PCOS

subjects.

 

(13,14) This is associated with differences in fat distribution.

Even in individuals with a nonobese BMI, a higher waist-to-hip ratio

is seen in those with PCOS compared to those without PCOS. (23) This

is supported

by the higher proportion of visceral adiposity measured by

ultrasound in lean PCOS patients compared to weight-matched control

subjects. (24)

 

Obesity also exacerbates several other metabolic abnormalities in

PCOS.

 

In comparison to lean women with PCOS, obese women with PCOS have

higher levels of testosterone and lower levels of luteinizing

hormone. (25-27)

 

Obese women with PCOS also have a dyslipidemia. At least one

abnormal lipid level is seen in 70% of women with PCOS. (2

 

The pattern of dyslipidemia found in the metablic syndrome, which

features elevated

triglycerides and low HDL cholesterol, has been reported in

association with obesity in PCOS, but this has not been found to

differ from weight-matched

control subjects. (29)

 

Studies controlling for insulin resistance have

found that the low HDL cholesterol and high triglycerides are

associated

with insulin resistance rather than with the presence of PCOS. (30)

 

Abnormalities of LDL cholesterol have not been found consistently in

PCOS. (31) However, even in those with a normal LDL level, Pirwany

et al. (32) have shown increased VLDL and small, dense LDL

cholesterol in PCOS relative to control subjects, as is seen in the

metabolic syndrome.

(33)

 

The final facet of the metabolic syndrome, hypertension, is uncommon

in PCOS. (31,34) However, this may be a matter of exposure. In a

retrospective study, women treated 20-30 years for PCOS were found

to have an increased prevalence of both hypertension and diabetes

compared

to weight-matched control subjects. (17,35)

 

In addition, some studies of 24-hour ambulatory systolic blood

pressure recordings in young women with PCOS show increases that are

predictive of the development of hypertension later in life. (36)

Thus, several

features of the metabolic syndrome overlap with features of PCOS.

 

In women with obesity, there may be an adverse clinical synergy

between features of both PCOS and the metabolic syndrome. Both of

these

conditions could predispose to CVD through common pathways.

 

The risk for CVD in the metabolic syndrome is well supported by

large epidemiological studies. In PCOS, retrospective studies based

on

menstrual abnormalities (which would mostly, but not exclusively, be

caused by PCOS) show increased cardiovascular and diabetes-related

deaths). (37,3 One challenge of these studies is the time lag

between

reproductive symptoms heralding PCOS and much later development of

CVD.

 

An assessment of women undergoing coronary angiography for chest

pain

found an excess of women with polycystic ovaries seen on ultrasound.

(39)

 

While neither endpoint--the need for angiography or the presence of

polycystic-appearing ovaries--is specific, this has encouraged

others to look more closely.

 

 

 

Coronary artery calcification was increased when examined in small

studies of women with PCOS. (40,41)

 

http://www.findarticles.com/p/articles/mi_m0682/is_4_21/ai_110262475

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