Comparison of estimates of insulin sensitivity in pre- and postmenopausal women using the insulin tolerance test and the frequently sampled intravenous glucose tolerance test.

We assessed insulin sensitivity in women comparing the insulin tolerance test (ITT) with the intravenous glucose tolerance test with frequent sampling and computer modeling (FSIVGTT) and evaluated the effects of hormonal therapy in postmenopausal women using both methods. This prospective study tested 18 premenopausal women and ten postmenopausal women randomized to receive either estrogen alone or estrogen with a sequential progestin for 6 months at a menopause research clinic. All subjects received an ITT and an FSIVGTT within 48-72 hours of each other in random sequence. Postmenopausal women were then randomized to receive either 0.625 mg conjugated equine estrogen for 6 months or 0.625 mg conjugated equine estrogen with medroxyprogesterone acetate, 10 mg, for 10 days each month for 6 months. Both the ITT and the FSIVGTT were repeated following hormonal therapy at 2 and 6 months. Plasma insulin and glucose were measured; insulin sensitivity was calculated after the ITT (Kitt) and the FSIVGTT (Si) at each visit in each group. A close correlation was found between Kitt and Si values at initial testing in both pre- and postmenopausal women and following both types of hormonal therapy (r = 0.76 for all tests, P < .001). A reduction in insulin sensitivity was observed in postmenopausal compared to premenopausal women; this occurred in five of ten postmenopausal women using the Kitt measurement and in four of ten women using Si. Estrogen replacement had a beneficial effect on insulin sensitivity. While Kitt increased by 24.2 +/- 9.6% (P < .05), the increase in Si (6.7 +/- 18%) was not significant because of the variability with this measurement. An attenuation in insulin sensitivity was seen with added progestin. Kitt values decreased by 17.7 +/- 7.7% and Si values by 31.9 +/- 12%. Similar findings were noted at 2 and 6 months. The ITT and FSIVGTT provide quantitatively similar information regarding insulin sensitivity in healthy women. A mild degree of insulin resistance appears to be present in some healthy postmenopausal women. Estrogen appears to improve insulin sensitivity, while added progestin may attenuate this beneficial effect.