The insulin resistant subphenotype of polycystic ovary syndrome: clinical parameters and pathogenesis☆

Abstract 

Objective

This study was undertaken to compare clinical and biochemical characteristics of the insulin resistant (IR) and non-IR subphenotypes of polycystic ovary syndrome (PCOS).

Study design

Infertile PCOS women were classified as IR (n=32) or non-IR (n=46) on the basis of fasting glucose and insulin levels. The incidence of acanthosis nigricans (AN), hirsutism, and ovulation in response to clomiphene citrate (CC) was compared between the 2 groups, along with serum levels of gonadotropins, and sex steroids. Blood samples from 28 PCOS patients and 8 controls were analyzed by enzymatic immunoassay for autophosphorylated insulin receptor (APIR) and total insulin receptor (TIR) content.

Results

Insulin resistance was associated with obesity (odds ratio [OR]=3.5, P < .05), AN (OR=6.0, P < .05), hirsutism (OR=3.1, P < .05), and resistance to CC (OR=5.0, P < .05). Mean levels of LH, LH/FSH ratios, and testosterone were lower in women with IR (11.5 ± 6.8 mIU/mL, 2.0 ± 1.0, and 56.6 ± 29.0 ng/dL, respectively) compared with women without IR (15.0 ± 13.4 mIU/mL, 2.4 ± 1.5, and 72.5 ± 29.8 ng/dL, respectively) (P < .05). Mean APIR/TIR ratios in IR women were lower than in non-IR women (P < .05 at 100 nmol/L of insulin) and controls (P < .01 at 1, 10 and 100 nmol/L insulin).

Conclusion

Patients with IR are more likely to be obese and have AN, hirsutism, resistance to CC, and lower LH, LH/FSH ratios, and testosterone levels. Furthermore, IR patients appear to have defective autophosphorylation of the insulin receptor, a key element in insulin action, and a possible mechanism for IR in PCOS.

Keywords:  Polycystic ovary syndrome, Insulin resistance, Hyperinsulinemia, Insulin receptor, Autophosphorylation