Metabolic syndrome linked to menstrual, hormonal, insulin irregularities in adolescence

Glueck CJ. J Pediatr. 2011;doi:10.1016/j.jpeds.2011.01.018.

Oligomenorrhea, polycystic ovary syndrome, sex hormones and insulin levels during adolescence may play a significant role in the genesis of metabolic syndrome and severe obesity in young adulthood, researchers report in a new study.

The prospective study of 237 white and 256 black schoolgirls compared information on menstrual cycles, insulin, sex hormone levels and metabolic syndrome gathered at age 14 years with the presence of class III obesity and metabolic syndrome at age 24 years. The researchers categorized participants as having regular menstrual cycles, oligomenorrhea or PCOS. Oligomenorrhea was defined as menstrual cycles of at least 42 days and PCOS was defined as oligomenorrhea combined with biochemical hyperandrogenism. Insulin was measured between ages 10 and 16 years.

Results revealed significant associations between metabolic syndrome at age 24 years and high childhood insulin levels, metabolic syndrome, PCOS and low sex hormone-binding globulin (SHBG) at age 14 years. A categorical model based on reports of oligomenorrhea collected from ages 14 to 19 years also identified race-specific top decile childhood insulin, race-specific bottom decile SHBG, PCOS and metabolic syndrome at age 14 years as predictors for metabolic syndrome at 24 years.

Severe obesity at age 24 years was also linked with black race, low SHBG and oligomenorrhea at age 14 years. The researchers noted no significant association between obesity and childhood insulin or metabolic syndrome at age 14 years, however. Black race, race-specific top decile childhood insulin, race-specific bottom decile SHBG, metabolic syndrome and PCOS at age 14 were implicated as predictors for class III obesity at 24 years.

These factors “may represent a critical, reversible pathway for the development of metabolic syndrome and class III obesity in young adulthood,” study researcher Charles J. Glueck, MD, medical director of the Cholesterol and Metabolism Center at The Jewish Hospital in Cincinnati, told Endocrine Today.

Glueck said there is an independent association between adolescent oligomenorrhea and adult impaired fasting glucose and type 2 diabetes, as well as a link between an increased risk for coronary heart disease among women with irregular menstrual cycles.

“Determining the degree of menstrual cycle irregularity in both adolescent and adult women is a simple clinical parameter, which is a valuable instrument to estimate the degree of metabolic and endocrine disorders,” he said.

After menarche, it is not normal in the ensuing years to have menstrual cycles 42 days or more apart, Glueck said, and menstrual irregularity and oligomenorrhea should trigger assessment of insulin, glucose, sex hormones, hyperandrogenism and PCOS early in adolescence, facilitating primary prevention of hyperinsulinemia, IFG, type 2 diabetes, metabolic syndrome, morbid obesity and full-blown phenotypic expression of PCOS.

Disclosure: Dr. Glueck reported no relevant financial disclosures.

More than 90% of girls have menarche by age 14 years, and one report by Chiazze et al indicates that only 2.5% of 15- to 19-year-old girls have oligomenorrhea, defined as menstrual cycle length longer than 40 days. The researchers evaluated the relationship between oligomenorrhea and sex steroid concentrations at age 14 years and the presence of metabolic syndrome and class III obesity at age 24 years. The presence of hyperandrogenism, assessed by measuring DHEA-sulfate and free testosterone levels, and oligomenorrhea were used to define PCOS. Insulin resistance was determined by measuring fasting insulin and fasting blood glucose concentrations. Metabolic syndrome was defined in the 14-year-old girls as three or more of the following criteria: triglycerides >111 mg/dL; HDL ≤50 mg/dL; fasting blood glucose ≥100 mg/dL; BMI ≥90th percentile for age; and BP ≥90% for age and height. Adult criteria for metabolic syndrome were used for the 24-year-old women (three or more of the following: waist circumference >88 cm; HDL <50 mg/dL; triglycerides ≥150 mg/d; fasting blood glucose ≥100 mg/dL; and systolic BP ≥130 and/or diastolic BP ≥85 mm Hg.

Not surprisingly, the researchers found higher free testosterone levels and larger waist circumferences in the 14-year-old girls with oligomenorrhea than in those with normal menstrual cycles. There was no difference between the groups in SHBG, other sex hormones, insulin, BMI or race. However, oligomenorrhea and low SHBG, the presence of metabolic syndrome, high insulin levels and PCOS diagnosis at age 14 years predicted metabolic syndrome at age 24 years. Black race was also a risk factor for morbid obesity at 24 years.

This study emphasizes the importance of diagnosing PCOS during adolescence, as PCOS in early adolescence predicts PCOS and metabolic syndrome in early adulthood. Because metabolic syndrome is a risk factor for early development of CVD and carbohydrate intolerance, it is essential that this condition is recognized and great efforts made to treat the comorbidities associated with the insulin resistance that is a key component of both PCOS and metabolic syndrome. Obesity is the most common cause of insulin resistance and, indeed, was a significant risk factor for later development of metabolic syndrome. The researchers did not discuss the outcome of adolescents who lost weight between 14 and 24 years of age, and this would be of interest. It seems logical that weight loss would decrease the risk for later development of metabolic syndrome and PCOS, and efforts should be redoubled to attempt weight loss in this cohort.

– Janet Silverstein, MD

Endocrine Today Editorial Board member

Disclosure: Dr. Silverstein reports no relevant financial disclosures.

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