Clinical features in women with polycystic ovaries: relationships to insulin sensitivity, insulin gene VNTR and birth weight

Objective: Polycystic ovaries are a common ultrasound finding, yet few of t hese women have many clinical features of polycystic ovary syndrome. Clinic al presentation may relate to degree of insulin resistance, common polymorp hism at the insulin gene VNTR, and birth weight. We therefore examined the relationship between insulin sensitivity, insulin gene VNTR genotype, birth weight and presence of polycystic ovaries/features of polycystic ovary syn drome in a normal population study. Design and Patients In 224 young women recruited as normal volunteers, ovar ian morphology was determined by transabdominal ultrasound and features of polycystic ovary syndrome were identified on clinical and biochemical exami nation. Insulin sensitivity was estimated from fasting glucose and insulin levels using the homeostasis model. Insulin gene VNTR genotypes were determ ined in women and their parents. Measurements and Results: Thirty-three per cent (74/224) had polycystic ova ries on ultrasound. These women had higher birth weights (P = 0.004), highe r insulin sensitivity (P = 0.02) and higher leptin levels for body mass ind ex (P = 0.04) than women with normal ovaries. However among women with poly cystic ovaries, increasing severity of clinical phenotype (based on number of features of: menstrual irregularity, acne, hirsuitism, serum testosteron e > 3 mmol/l and LH > 10 IU/l) was associated with decreasing insulin sensi tivity (P < 0.0001) and related to paternally transmitted insulin gene VNTR class III alleles (P = 0.03). Conclusion: Women with polycystic ovaries on ultrasound have increased insu lin sensitivity and possible leptin resistance, which could predispose to f uture weight gain. However, in these women the appearance of clinical featu res of polycystic ovary syndrome is related to insulin resistance and insul in gene VNTR class III alleles.