Hormone replacement therapy alters insulin sensitivity in young women with premature ovarian failure

In this study, we report the effects of cyclic hormone replacement therapy on carbohydrate metabolism in six women with premature ovarian failure. Using tolbutamide-modified iv glucose tolerance tests patients were evaluated during three different intervals of their second treatment cycle: no hormone replacement, estradiol-only (E2-only) replacement, and E2-plus-medroxyprogesterone acetate (MPA) replacement. Insulin sensitivity and glucose effectiveness were derived using insulin and glucose levels obtained from tolbutamide-modified iv glucose tolerance tests and analyzed with the minimal model computer program. The mean insulin sensitivity (x 10(-4)/min/microU.ml) significantly decreased from 4.0 +/- 0.8 during no hormone replacement and 3.8 +/- 0.8 during E2-only replacement to 2.6 +/- 0.5 (x 10(-4)/min/microU/ml) during E2-plus-MPA replacement (P < 0.005). Glucose effectiveness did not change as a function of the phase of hormone replacement therapy. These findings indicate a significant decrease in sensitivity to insulin associated with MPA treatment but no observable change in insulin sensitivity during the E2-only phase of cyclic steroid replacement therapy in young women. Our results support the hypothesis that impairment of insulin-mediated glucose uptake during the luteal phase of the menstrual cycle is due to increased progesterone secretion.