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/muU.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/muU/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.