Influence of hormonal contraceptives on carbohydrate and lipid metabolism in the rat

Abstract

The effect of low, physiological doses of hormonal contraceptives on carbohydrate and lipid metabolism in the female rat was investigated. Animals were treated, by subcutaneous njection, for 14 days with a combination of 5 μg/kg ethynyl estradiol + 50 μg/kg dl-norgestrel, 5 μg/kg ethynyl estradiol + 400 μg/kg norethindrone acetate and with the single components only. Blood glucose in fasted animals was not altered. There was a dose-dependent increase in glycogen deposition in liver. This effect was confined to the estrogenic component and was dependent on the presence of the adrenal gland. The sensitivity of the organism towards exogenous insulin was not changed. In an insulin sensitive system, e.g. in isolated fat cells, the conversion of glucose-1- 14C to 14CO 2 was not significantly altered, neither in the presence nor in the absence of insulin. Treatment of rats with ethynyl estradiol was associated with a highly significant increase in serum triglycerides, a transient reduction in serum total cholesterol and a decrease in total lipids in liver. Similar effects were observed after administration of the combination of ethynyl estradiol + dl-norgestrel. The estrogen-induced increase in serum triglycerides was, however, abolished by simultaneous treatment with norethindrone acetate. Liver lipids remained reduced. Neither gestagen substantially altered lipid metabolism. Free fatty acids in serum of fasted and fed rats were unaltered after ethynyl estradiol. There was no increased lipolytic rate with epinephrine, as measured in isolated fat cells. The antilipolytic effect of insulin was not significantly changed in animals treated with ethynyl estradiol and ethynyl estradiol + dl-norgestrel. The experiments demonstrate that the estrogenic component of hormonal contraceptives is mainly responsible for the metabolic changes seen in the rat. It is suggested that the gestagens may play an important role in modifying the effects of estrogens on carbohydrate and lipid metabolism.