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graphic measures of cardiac mechanics (20), ultrasono-

FIGURE 1 graphic measurement of carotid artery intima-media thick-


Cardiovascular (CV) risk according to level of insulinemia.
ness (21), and measurement of endothelium-dependent leg
The polycystic ovary syndrome (PCOS) itself carries more CV blood flow (22). Therefore, although unproved, it seems
risk than control, even at equivalent insulin levels. Hyperin- reasonable to suppose that risk factors predict CV outcome
sulinemic PCOS patients have even more CV risk factors. among women with PCOS.
These differences are statistically significant when corrected
for body mass index (P!.004) and differ between the PCOS BMI versus Insulin Resistance and Excess
groups as well as between each PCOS group and control Risk
(P#.05). The mean insulin levels were 52.0, 53.7, and 181.3
pmol/L for controls, normoinsulinemic PCOS women, and The aggregation of CV risk factors in PCOS patients has
hyperinsulinemic PCOS women, respectively. been previously observed (1, 3, 9, 12, 23, 24), but the relative
contributions of BMI and insulin levels remain controversial.
Studies using obesity or insulin as univariate predictors of
CV risk have found statistically significant relationships (9,
12, 25), but few studies have examined the interaction di-
rectly. After correction for BMI, our data show significant
relationships of insulin level with waist circumference and
lipid levels but not with waist-to-hip ratio, fasting glucose
level, or blood pressure. Table 4 shows that among the
hyperinsulinemic PCOS patients, CV risk factors are up to
five times as prevalent as among the normoinsulinemic
PCOS patients.
Among women with PCOS, CV risks have been reported
to vary according to degree of obesity: Lean PCOS women
are reported to have fewer lipid abnormalities (26), and
obese PCOS women have abnormalities in blood pressure
and blood glucose levels, whereas their lean counterparts
do not (12). Undiagnosed type 2 diabetes mellitus is very
prevalent, and the rate of conversion to frank type 2 dia-
betes mellitus is at least fivefold that of obese nonPCOS
women (27).
In healthy subjects, a threshold effect of obesity on insu-
lin resistance has been described, with insulin resistance
appearing at a BMI "26.8 (28). Patients with PCOS have
higher insulin levels than controls across the range of BMI
(Figure 2) (29), and both lean and obese women with PCOS
have been shown to be insulin resistant (30). This suggests
that PCOS itself confers insulin resistance, with the added
effect of obesity. Despite this interdependence, we were able
to demonstrate that insulin resistance correlated with CV risk
even after correction for BMI. This supports the argument
Mather. Hyperinsulinemia in PCOS. Fertil Steril 2000.
that insulin resistance per se is important in determining
cardiovascular risk and suggests that the role of obesity in
records for women diagnosed with PCOS at least 18 years determining risk is mediated at least in part through its
earlier and reported a standardized mortality ratio for isch- augmentation of insulin resistance.
emic heart disease of 1.4 (95% CI, 0.75–2.4, P ! not
significant) on the basis of 13 ischemic heart disease deaths Hyperinsulinemia and Metabolic
among 59 total deaths in 786 women. Nonepidemiologic Abnormalities in PCOS
data provide some evidence of an excess of vascular disease Hyperinsulinemia in PCOS has been found to correlate
in women with PCOS. Women undergoing cardiac catheter- with low HDL and high triglyceride levels (12), as was seen
ization demonstrated a correlation between the extent of in our patients. This combination is frequently associated
coronary atherosclerosis and the presence of morphologi- with small, dense LDL particles, which carry greater cardio-
cally polycystic ovaries (19). Abnormalities in preclinical vascular risk than more buoyant LDL particles (31). We also
measures of vascular disease among women with PCOS observed an increase in total and LDL cholesterol levels that
have also been demonstrated, using Doppler ultrasono- was proportional to the insulin level among the PCOS

154 Mather et al. Hyperinsulinemia and CV risk in PCOS Vol. 73, No. 1, January 2000

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