Insulin resistance and clomiphene resistance—Is there any correlation?

Abstract

Objective: There is a recent trend to use insulin sensitizers in women with Polycystic Ovarian syndrome (PCOS). A debate is on as to which subset of women with PCOS benefit with this therapy. Our aim of the study was to evaluate the insulin sensitivity in PCOS women who ovulate (responders) and do not ovulate ( nonresponders) with clomiphene citrate and also normal ovulatory non PCOS women. Design The PCOS women who did not ovulate with maximum dose of clomiphene citrate (200mg/ day) were selected for the study. Their insulin status was evaluated by fasting insulin levels, fasting glucose to insulin ratio and insulin sensitivity by short insulin tolerance test. They were compared with insulin status of PCOS women who responded to clomiphene citrate 100 or 150mg/day dose schedule. The comparison was also done with the insulin status of normal ovulatory women with infertility. Material & methods This prospective study was conducted in Reproductive medicine Unit of Christian medical College with approval of the institutional review board. Sixty clomiphene resistant women with PCOS (group I) were selected for the trial. 23 responders (group II) and 21 normally ovulatory women (group III) were also evaluated. Their body mass indexes, waist to hip ratio were recorded. The fasting blood was taken for glucose and insulin levels. Insulin sensitivity was measured using the short insulin tolerance test. In brief an intravenous bolus injection of actrapid insulin (0.05 U/kg) was given. Blood samples were drawn from the contra lateral arm at 5 min before and at 3, 5, 7,9,12 and 15 min after insulin injection. Glucose was then injected i.v. at 15 min to prevent a fall in plasma glucose level. The rate of fall of blood glucose was calculated from the linear regression of all values between 3 min and 15 min; this rate of fall was taken as the index of insulin sensitivity. Results. ( Table I) Tabled 1 The body mass index and waist to hip ratio were comparable in all 3 groups. The fasting insulin was significantly higher in nonresponders as compared to responders and ovulatory women. The multivariate analysis showed that fasting insulin was significantly higher in nonresponders even after adjusting for BMI. There was trend towards lower glucose- insulin ratio in nonresponders, though this was not statistically significant. Glucose-insulin ratio of < 4.5 is considered as index of insulin resistance. 28.3% women of group I, 4.3% of group II and none in group III had glucose- insulin ratio < 4.5. There was trend towards higher insulin resistance in nonresponders as evaluated by the insulin sensitivity. Conclusions The clomiphene resistant PCOS women are more insulin resistant than clomiphene responder PCOS. The insulin sensitivity seems to be similar in clomiphene responder PCOS and normally ovulatory non PCOS women. Therefore clomiphene resistant PCOS women should benefit with insulin sensitizers.