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  • Title: The effect of Norplant on glucose metabolism under hyperglycemic hyperinsulinemic conditions.
    Author: Shamma FN, Rossi G, HajHassan L, Penzias AS, Connoly-Diamond M, Jones E, Diamond MP.
    Journal: Fertil Steril; 1995 Apr; 63(4):767-72. PubMed ID: 7890060.
    Abstract:
    OBJECTIVES: To assess the impact of a levonorgestrel-releasing implant contraceptive (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA) on glucose metabolism. DESIGN: Prospective evaluation of insulin action and secretion in women under hyperglycemic hyperinsulinemic clamp conditions in the midfollicular phase before and 8 weeks after Norplant placement. SETTING: Yale University Clinical Research Center. PARTICIPANTS: Seven previously normally cycling, nonobese, nondiabetic women participated in the study. INTERVENTIONS: Norplant insertion. MAIN OUTCOME MEASURES: Basal levels of glucose and insulin, as well as glucose-mediated insulin secretion, glucose uptake, and tissue sensitivity to insulin were assessed using the hyperglycemic hyperinsulinemic clamp technique before and after Norplant insertion. RESULTS: Norplant placement did not alter the fasting glucose or insulin levels. However, it was associated with a significant 37% increase in the first phase insulin response from a control level of 51 +/- 8 to 70 +/- 10 microU/mL (conversion factor to SI unit, 7.175), and a significant 48% increase in the second phase insulin response from 60 +/- 5 to 89 +/- 8 microU/mL. In association with this increase in insulin levels after Norplant insertion, total mean body glucose uptake (M) increased from 8.08 +/- 0.91 to 9.53 +/- 0.95 mg/kg per minute. However, when expressed as the total body glucose uptake per unit of insulin, the M:I ratio (a measure of tissue sensitivity to insulin) decreased significantly from a mean of 0.12 +/- 0.02 to 0.10 +/- 0.01 mg/kg per minute per microU/mL. CONCLUSION: Although Norplant insertion does not alter basal glucose and insulin levels, tissue sensitivity to insulin under hyperglycemic hyperinsulinemic conditions is decreased after Norplant insertion. Earlier studies on the effect of oral contraceptive (OC) use on glucose metabolism have resulted in mixed findings. OCs containing levonorgestrel have been reported as having the greatest effect on glucose metabolism and insulin response. This article reports on the effect of Norplant on glucose metabolism in 7 women. Hyperglycemic clamp studies were also performed on the study subjects in the midfollicular phase before and 8 weeks after Norplant insertion. Statistical analysis was performed using the paired t-test. Blood samples for glucose and insulin measurements were taken every 10 minutes during the 30-minute basal period, at 2-minute intervals during the initial dextrose introduction phase, and in intervals of 5-10 minutes for the remaining time. Total study time was 2 hours. There was no significant difference between measurements before and after Norplant use. However, it was associated with a significant 37% increase in the first-phase insulin response from 51 +or- 8 to 70 +or- 10 mcU/ml and a significant 48% increase in the second-phase insulin response from 60 +or- 5 to 89 +or- 8 mcU/ml. Tissue sensitivity to insulin decreased with Norplant use.
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