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Hormonal Contraceptives: Adverse Effects, P4


Anticonceptivos hormonales; Contraceptifs Hormonaux; Hormonale Kontrazeptiva

Effects on the ears. In the Royal College of General Practitioners study of oral contraception in the UK, by 1981 there had been 13 cases of newly occurring otosclerosis in each of the groups of oral contraceptive users (101 985 woman-years) and controls (146 534 woman-years) this showed a non-significant relative risk of 1.29. Although, by analogy with pregnancy, it may be prudent to suppose that oral contraceptives could exacerbate pre-existing otosclerosis, the data do not support the view that the condition is associated with their use. Similarly, the Oxford Family Planning Association contraceptive study of 17 032 women followed for up to 26 years found no association between oral contraceptive use and the development of a range of ear diseases, including otosclerosis.

Effects on the eyes. Analysis of data from 2 large UK cohort studies suggested that oral contraceptive use does not increase the risk of eye disease, with the possible exception of retinal vascular lesions. Retinal vein thrombosis has also been reported after the use of emergency contraception. The patient presented with a 10-day history of blurred vision that started the day after taking a regimen of ethinylestradiol with norgestrel the condition resolved after 2 months of treatment with low-dose aspirin.

Effects on fertility. After stopping hormonal contraceptives some patients may experience amenorrhoea, anovulation, and infertility. This infertility, however, has been shown by most studies to be only temporary.

Data from the Oxford Family Planning Association study have indicated that impairment of fertility after oral contraceptives was only very slight and short-lived in women who had previously had a baby. In nulliparous women aged 25 to 29 years impairment of fertility was more pronounced but the effect had almost entirely disappeared after 48 months. In nulliparous women aged 30 to 34 years the duration of impairment was longer but, again, this was not permanent as by 72 months after stopping oral contraceptive use the numbers of women who had not conceived were similar to a group who had previously used non-hormonal methods of contraception. In contrast to women using intra-uterine devices, in whom long-term use was associated with greater impairment of fertility than short-term (less than 42 months) use, there appears to be no association between fertility and duration of oral contraceptive use. However, a later survey, although concurring that the effects were transient, did find a relationship between duration of use of combined oral contraceptives and subsequent time to pregnancy.

Oral progestogen-only preparations do not appear to have a significant effect on fertility. Smaller studies have also indicated that injectable progestogen-only contraceptives have no long-lasting effects on fertility but it has been suggested that a return to ovulation occurs significantly earlier in prior norethister-one enantate users than in medroxyprogesterone users.

Infertility may also be related to the presence of pelvic inflammatory disease for further details concerning the role of oral contraceptives in this disorder, see Pelvic Inflammatory Disease, below.

Effects on the gallbladder. Data from the Royal College of General Practitioners’ (RCGP) oral contraception study accumulated up to December 1979 revealed no overall increased risk of gallbladder disease in the long-term, despite the indications of earlier data and other studies relating to short-term use. Further studies’ have identified an increased risk of gallbladder disease in oral contraceptive users under the age of 30 or 20, respectively. A systematic review also found that oral contraceptives were associated with a slightly and transiently increased risk of gallbladder disease. However, the results of separate studies varied considerably and the reviewers highlighted a number of possible confounding factors and biases, nonetheless, it was concluded that newer low-dose contraceptives (less than 50 micrograms of oestrogen) were less likely to cause problems than older formulations. Later data from the RCGP study showed an increase in risk of mild hepatitis during the first 4years of oral contraceptive use, possibly reflecting gallstone-associated cholestasis. This risk then decreased to less than that seen in women who had never used oral contraceptives.

Effects on the gastrointestinal tract. Several studies, ep-idemiological data, and a meta-analysis, have shown a weak association between oral contraceptive use and the onset of Crohn’s disease or ulcerative colitis. However, the suggestion that oral contraceptives have an aetiological role in chronic inflammatory bowel disease cannot be regarded as established.

The rate of relapse of Crohn’s disease in women taking oral contraceptives has also been studied. Although one study reported an increased risk of relapse in women who had taken oral contraceptives in the past, both this study and another prospective cohort study found no increase in risk in current users. These results may have been influenced by smoking, or changes in oestrogen dose and progestogen content.

Women with inflammatory bowel disease may be offered the same contraceptive choices as other women, although oral contraceptive absorption, and hence efficacy, may be reduced when there is small bowel involvement or malabsorption.

Effects on lipids. Combined oral contraceptives have been reported to be associated with an excess risk of various adverse cardiovascular events (see above). Because other epidemiologi-cal evidence suggests that the composition of blood lipids may be one of several factors involved in the aetiology of some of these disorders, many workers have investigated the biochemical profiles of women taking various formulations of oral contraceptives. Results have often been conflicting as the net effect is the result of opposing actions of the oestrogen and the progestogen components, and depends on the ratio between these. In general, the oestrogen component increases triglycerides, but decreases low-density lipoproteins, whereas the progestogen component tends to decrease high-density lipoproteins and increase low-density lipoproteins, particularly if it is androgenic (19-nortestosterone-derived progestogens). Newer non-androgenic pro-gestogens such as desogestrel and gestodene appear to have a less detrimental effect on serum lipids. However, the contribution of these lipid changes to the incidence of cardiovascular disease in oral contraceptive users is uncertain. In particular, contrary to expectations, desogestrel and gestodene appear to be associated with a higher risk of venous thromboembolism than older progestogens (see above).

Some references to the effects of various oral contraceptives on serum lipid profiles are given below.

For further details concerning the proposed role of the various serum lipids and subfractions in the aetiology of cardiovascular disease, see Hyperlipidaemias.

For reports of pancreatitis secondary to hyperlipidaemia associated with the use of combined oral contraceptives, see below.

Effects on the liver. The use of combined oral contraceptives has been rarely associated with the benign liver tumours, hepatic adenoma and focal nodular hyperplasia (see under Carcinogenicity, above).

Hepatitis possibly associated with gallstones has also been reported (see Effects on the Gallbladder, above).

Effects on mental state. Changes in mood and affect have been reported with oral contraceptives, and the onset of depression is a common reason given for stopping use. Nonetheless, a review concluded that most women taking oral contraceptives actually experienced beneficial effects, with less variability in affect across the menstrual cycle and less negative affect during the menstrual phase compared with non-users. However, there may be a subgroup of women predisposed to negative changes in mood and affect because of factors such as a history of depression, premenstrual mood symptoms before oral contraceptive use, a history of mood symptoms related to pregnancy, or a family history of mood complaints related to oral contraceptives. A lower ratio of progestogen to oestrogen was associated with more negative mood changes in women with a history of premenstrual emotional symptoms, while a higher ratio was associated with negative changes in women without such a history. In addition, monophasic regimens appeared to have a greater stabilising effect than triphasic preparations. A number of possible mechanisms have been suggested to explain how combined hormonal contraceptives might influence mood.

Cohort studies of injectable and implantable progestogen-only contraceptives found no overall change in depressive symptom score. A small increase in depressive score noted at the 2-year follow-up of implant users was found to occur in women who also had a decrease in relationship satisfaction, which the authors concluded was independent of contraceptive use. Another study found an association between injectable medroxyprogesterone acetate and depressive symptoms, but other factors that might have influenced this result were also identified and another explanation could not be ruled out.

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