PCOS Development May Begin With Insulin Resistance


INDIAN WELLS, CALIF. — Insulin resistance precedes and may set the stage for hyperandrogenism in peripubertal girls at risk for polycystic ovary syndrome, researchers concluded in what is believed to be the first prospective, longitudinal study of PCOS development.

Dr. Marc J. Kalan and his associates at the University of Southern California, Los Angeles, enrolled 57 prepubescent Hispanic girls aged 8–13 years who were at high risk for polycystic ovary syndrome (PCOS) because they were obese (defined by the investigators as a body mass index greater than or equal to the 85th percentile for age and sex), and had a first-degree family member with diabetes.

At yearly intervals for a mean of 4 years, the girls underwent interviews, physical examinations, dual-energy x-ray absorptiometry, and MRI studies to assess body composition and visceral fat accumulation, fasting serum hormone measurements, and oral and intravenous glucose tolerance testing. Dr. Kalan reported the results at the annual meeting of the Pacific Coast Reproductive Society.

Of the 57 girls, 15 (26%) developed what investigators termed a “PCOS-like” condition, in that their menses became irregular at least 2 years after menarche and they had clinical evidence of androgen excess.

No differences were seen between these girls and study subjects who did not develop PCOS-like findings in terms of adiposity, prepubertal insulin and sex hormone levels, or the age at menarche (average, 12 years).

However, within a year of menarche, they were significantly more insulin resistant than their peers (mean insulin sensitivity index [ISI]), 1.2 M/mU per liter, compared with 1.6 M/mU per liter), reported Dr. Kalan of the division of reproductive endocrinology and infertility at USC.

The girls' testosterone levels were similar to those of girls who did not develop PCOS-like findings at 1 year post menarche.

However, at 2 years post menarche, they had significantly higher mean testosterone levels (47.5 ng/dL, compared with 22.5 ng/dL).

The insulin resistance disparity widened during the second year post menarche (mean ISI, 1.2 M/mU per liter vs.1.8 M/mU per liter).

All differences in study parameters persisted after statistical adjustment for adiposity, the researcher reported.

The study results offer important evidence suggesting that testosterone is not the driver of events leading to PCOS. “Insulin resistance came first,” Dr. Kalan commented in an interview.

Assessing insulin values, specifically, insulin resistance, “may be clinically useful to predict PCOS in an overweight, high-risk [Hispanic] population,” the study investigators concluded.

Dr. Kalan said the group is still following the girls and evaluating other factors such as leptin.

Future research may be aimed at early prevention.

“Obviously, the next thing to do is to intervene earlier. Maybe you could head this off,” he said.

Dr. Kalan's research was supported by the National Institutes of Health.

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