Oral contraceptives, norethynodrel and mestranol: effects of glucose tolerance, tissue uptake of glucose-U- 14 C and insulin sensitivity.

Abstract

The study was undertaken to determine which of the 2 steroidal agents commonly used in oral contraceptives - norethynodrel or mestranol - is responsible for changes in glucose tolerance and to investigate possible roles of liver depot fat and diaphragm muscle. 11-week-old female rats were used. Experimental diets were enriched with either mestranol norethynodrel or both steroids. 1 group was fed a control (non-supplemented) diet. In the experimental groups the daily intake of steroids was about .1 mg norethynodrel and/or 1.5 mg mestranol/kg body weight. No significant differences in glucose tolerance curves appeared among the 4 groups after 2 weeks of steroid treatment. After an additional 2 weeks higher glucose levels were seen in the steroid-treat ed rats than in the control rats. Analysis of variance showed norethynodrel responsible for the overall increase in levels in the steroid-treated rats. Though mestranol alone caused no significant departure from the control pattern the addition of this compound appeared to partially reverse the effect of norethynodrel. In the combi nation and mestranol groups the rates of gastric emptying and gastrointestinal absorption of an oral glucose load were significantly lower than in the norethynodrel and control groups. Mestranol appeared to be the main factor causing the difference. No significant differences were seen in the uptake of radioactivity from glucose-U-carbon-14 by liver or diaphragm muscle between control and experimental rats. Adipose tissue however took up significantly less radioactivity in the combination and norethnodrel groups than in the control and mestranol groups norethynodrel having been the major causat ive agent. Syntheses of fatty acids and nonsaponifiable lipid were found to be significantly lower in the steroid-treated tissues. The conversion of glucose to CO2 and glycogen was significantly increased by insulin in the control and treated groups; the control tissues were more sensitive in this respect. The lower rates of gastric emptying and gastrointestinal absorption in rats treated with mestranol or its combination with norethynodrel though significant statistically apparently are too similar to the normal rates to have appreciable aeffects on blood glucose levels or rates of glucose metabolism in various tissues.