Adverse effects on carbohydrate and lipid metabolism

It is widely known that hormonal contraceptives(  HCs)  use can lead to an impairment of carbohydrate and lipid metabolism which are important risk factors for cardiovascular diseases.

These effects occur with progestin-only contraceptives as well as with contraceptives containing estrogens.  HCs may interfere with glucose metabolism, in part by creating an effect of peripheral insulin resistance and in part by diminishing the insulin-secreting capacities of the islets of Langerhans. It is shown that deterioration of glucose tolerance in the 1st trimester of oral contraceptives use is due to the synthetic estrogen, while hyperinsulinism after 6th month of use is due to the progestin component.

The early deterioration of glucose tolerance could be due to a direct action of estrogen on the pancreas, where specific estrogen receptors have been identified. The reduction of glucose levels by estrogen is due to reduction of glucogenolysis with an increase of hepatic gluconeogenesis. 

These effects may be explained by the action of estrogens on insulin and glucagon: estrogen inhibit the secretion of glucagon On the other hand,  progestins augment insulin and glucagon secretion without modifying their ratio in the portal vein (1,2). Hyperinsulinism is observed in women using combined hormonal contraceptives(COC)  or progestins only, whether or not there is a deterioration of glucose tolerance.

This effect which can appear after 3 months of use,  continues as long as HCs are used.  The determinations of insulin secretion are more reliable if peptide C in plasma is determined, as it is released by the pancreas in an equimolar amount with insulin and is not retained by the liver.  The hyperinsulinism is due to a hypersecretion and not to a diminution in degradation of insulin. So, probable pill-induced insulin resistance is comparable to that of pregnancy(1,2,3).

Although all progestins used in contraception, potentially,  induce insulin resistance with hyperinsulinism, the effect seems to be largely dependent on the type of progestin used and are more marked with 19 nortestosterone derivatives than with 17 alpha hydroxy proge sterone, because of the structural similarity of 19 norsteroids (4). The most notable changes seem are seen with Levonorgestrel (LNG),  mono or triphasic,  and are minimal   with   the   low-dose   COC   containing   third-generation   progestins (desogestrel and gestodene)  (5,6,7)

In fact,  was reported that women taking triphasic combined oral contraceptives develop, after three months from the start of the treatment ,a significant increase of the plasma glucose concentration and the plasma insulin response to oral glucose. While,  fasting plasma cholesterol ,HDL-cholesterol   and   LDL-  cholesterol   concentrations   did   not   change   as compared with baseline values,  nor did the ratio of total cholesterol to HDL-cholesterol. While plasma triglyceride levels increased significantly. (3) The effects of HCs on serum lipid levels depend on the dose of estrogen and dose and type of progestin.

Generally, ethinylestradiol (EE)causes an increase in triglycerides and HDL-cholesterol, while progestins tend to increase total cholesterol and decrease HDL-cholesterol. The evaluation of impact on lipid and carbohydrate profiles of two combined oral contraceptives containing 20 mcg EE/ 100 mcg LNG and 30 mcg EE/  150 mcg LNG showed similar effects for both preparations.  Although the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant(8,9).

So, low-dose combined HCs seem to have slight or no effect on cholesterol, HDL-cholesterol and triglycerides but there are only minimal differences with the higher doses pill. Low-dose progestin-only pill, may have deleterious effects.

Insulin-dependent diabetes in adolescents is a relative contraindication.  Were investigated the eventual different effects of non hormonal contraception(NHC), combination oral contraception (COC),  and depo-medroxyprogesterone acetate (DMPA) on lipids, in women with recent gestational diabetes mellitus(GDM).

This observational cohort study of 972 nondiabetic, normotensive, postpartum women showed that DMPA users gained significantly more weight compared with NHC and combined HC users(P < 0.0001). Patterns of change in LDL cholesterol,  and triglycerides were not significantly different among groups.  HDL cholesterol change differed only between COC and NHC groups (10).

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