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Hormonal Contraceptives: Adverse Effects, P2


Anticonceptivos hormonales; Contraceptifs Hormonaux; Hormonale Kontrazeptiva

Ectopic pregnancy. All methods of contraception effectively reduce the risk of ectopic pregnancy overall by reducing the rate of pregnancy. However, when contraception fails the proportion of pregnancies that are ectopic is higher for users of oral and in-tra-uterine progestogen-only contraceptives and levonorgestrel implants than in the general population. There is no increase in the proportion of ectopic pregnancies for methods that inhibit ovulation more reliably, such as combined oral contraceptives and medroxyprogesterone acetate depot injection.

A small number of cases of ectopic pregnancy after failure of emergency contraception, with both the Yuzpe regimen (oestrogen plus progestogen) and progestogen-only contraception, have been reported. However, data from clinical studies and postmarketing surveillance have shown that when levonorgestrel emergency contraception does rarely fail, there is no increase in the chance of ectopic pregnancy occurring.

Effects on body-weight. Weight gain has been reported as an adverse effect of combined oral contraceptives, but there is no strong evidence from clinical studies to confirm that they have a significant effect on weight. However, there is some evidence that weight gain might be associated with medroxyprogesterone acetate when given as a long-acting injectable contraceptive. There have been reports of both weight gain over 5 years, and no change in weight over 10 years, in women using medroxyprogesterone compared with those using a copper IUD. Studies in adolescents using medroxyprogesterone or an oral contraceptive for 12 or 18 months have reported more weight gain in those using medroxyprogesterone, and that significant weight gain was more likely in those who were overweight when contraception was started. The risk of weight gain, however, may be confounded by a number of factors including age, race, diet, exercise, and prior pregnancy.

For discussion of a possible association between obesity and oral contraceptive failure, see Obesity, under Precautions, below.

Effects on carbohydrate metabolism. The potential effects of oral contraceptives on carbohydrate metabolism are of concern because impaired glucose tolerance, hyperinsulinism, and insulin resistance contribute to atherogenesis and cardiovascular disease. Early studies suggested that the prevalence of abnormal glucose tolerance in oral contraceptive users was increased from about 4 to 35%. This decreased glucose tolerance was found to be related to oestrogen dose, particularly those greater than 75 micrograms daily, and to the type of progestogen. Marked hyperglycaemia has been associated with contraceptives containing high doses of oestrogen but is not seen with combined oral contraceptives used currently, which contain lower doses of oestrogen. Progestogens have little effect on glucose tolerance, but are associated with hyperinsulinaemia. This effect is dose-dependent, and levonorgestrel has the most potent effect, with desogestrel, gestodene, and norethisterone reported to have less effect. Combined oral contraceptives can also induce insulin resistance it is believed that the oestrogen is responsible and that the progestogen modifies this effect.

Despite evidence of these effects, more recent studies of lower-dose preparations containing desogestrel, levonorgestrel, or norethisterone have found little or no effect on various measurements of carbohydrate metabolism this lack of effect has also been confirmed in a meta-analysis of studies of hormonal contraceptive use in non-diabetic women although it was noted that no strong statement could be made since few studies compared the same types of contraceptives and some had large drop out rates. Also, data from the Nurses’ Health Study indicate that oral contraceptive use does not appear to increase the risk of developing type 2 diabetes mellitus. However, a study in the USA of breast-feeding women of Hispanic origin who had experienced recent gestational diabetes, suggested that the use of progestogen-only, but not combined, contraceptives was associated with an increased risk of developing type 2 diabetes mellitus in this group.

Injectable progestogen-only contraceptives have been reported in epidemiological studies to be associated with an increase in the incidence of type 2 diabetes mellitus. However, metabolic studies in lean, non-diabetic women have generally found no effect on glucose concentrations, suggesting that obesity or weight gain associated with injectable progestogen-only contraceptive use may play a role.

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