Objectives: It has been suggested that normal women receiving oral contraceptives (OC) may develop a series of metabolic side-effects which relate to the risk of cardiovascular disease. These metabolic disturbances include changes in glucose and insulin metabolism, raised serum lipid and lipoprotein concentrations and elevated blood pressure. All these changes indicate that OC might cause insulin resistance. We have prospectively examined the effect of OC on insulin resistance and lipid metabolism including Lp(a) values.
Patients: The study group comprised 13 normally menstruating Chinese women.
Design: The study subjects were given a combined triphasic oral contraceptive which was administered on a 21-day on, 7-day off medication cyclic regimen, the first pill being administered on day 5 from the beginning of menses. The metabolic investigations were carried out during luteal phase before OC and again the third week of the third month of OC administration.
Measurements: Metabolic evaluation including insulin secretion and insulin-mediated glucose uptake were evaluated by oral glucose tolerance test and the modification of insulin suppression test. Fasting triglyceride, cholesterol, HDL-cholesterol and Lp(a) concentrations were also measured.
Results: The plasma glucose and insulin responses during a 75-g oral glucose challenge increased significantly (P < 0.05 and P < 0.03, respectively). The steady-state plasma glucose (SSPG) concentrations achieved during constant infusion of glucose, insulin and somatostatin increased significantly after 3 cycles of OC administration (glucose 7.5 +/- 0.8 vs 12.4 +/- 0.7 mmol/l, P < 0.001) while the steady-state plasma insulin (SSPI) concentrations were relatively similar (410 +/- 14 vs 391 +/- 7 pmol/l, NS). Plasma triglyceride levels increased significantly (0.81 +/- 0.12 vs 1.09 +/- 0.19 mmol/l, P < 0.03) following OC administration. Fasting plasma cholesterol, HDL cholesterol and calculated LDL cholesterol concentrations did not change as compared with baseline values, nor did the ratio of total cholesterol to HDL cholesterol. The Lp(a) concentrations did not change during the administration of OC (81 +/- 25 vs 71 +/- 21 mg/l, NS).
Conclusions: These data indicated that intake of OC for 3 cycles induced glucose intolerance, hyperinsulinaemia and insulin resistance in normal menstruating Chinese women. These changes occurred in association with elevated plasma triglyceride concentrations and no alteration in Lp(a) or other lipid values.
PIP: In Taipei, Taiwan, physicians started 13 normally menstruating women on an isocaloric diet (30 kcal/kg; 50% carbohydrate, 30% fat, and 20% protein) and administered a combined triphasic oral contraceptive (OC) to evaluate the effect of the OC on insulin resistance and lipid metabolism including Lp(a) values. (Lp(a) levels may be a risk factor for coronary heart disease.) After three months of taking OCs, the plasma glucose concentration increased significantly (p 0.05). The plasma insulin response to oral glucose was also significantly higher than before OC use (p 0.03). The steady state plasma glucose concentration during constant infusion of glucose, insulin, and somatostatin was much higher three months after OC administration than before OC administration (12.4 vs. 7.5 mmol/l; p 0.001). After three cycles of OC use, the only fasting plasma lipoprotein that increased significantly was triglyceride (0.81 vs. 1.09 mmol/l; p 0.03). The Lp (a) levels stayed essentially the same. OC use decreased significantly the concentration of all serum steroids except DHEAS. These findings indicate that administration of a triphasic low dose OC for three cycles caused glucose intolerance, hyperinsulinemia, and insulin resistance in normal women. It also raised plasma triglyceride concentrations, but did not affect Lp(a) and other lipid values.