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Hepatobiliary complications of oral contraceptives.

Complications secondary to the use of oral contraceptive agents are rare. Hepatobiliary complications, while often dramatic in presentation, occur infrequently. In a patient without predisposing conditions to complications, the benefits achieved with estrogen/progesterone products outweigh the risks. Those conditions that would absolutely and relatively contraindicate the use of oral contraceptives are listed in Table 4. Patients with a past history of liver disease in whom liver function tests have returned to normal may tolerate the introduction of oral contraceptives. They need to be monitored closely for adverse reactions. Patients who have experienced cholestatic jaundice of pregnancy should avoid all contraceptives because of a high risk of disease recurrence. Women whose first-degree relatives have experienced cholestasis of pregnancy or oral contraceptive-induced cholestasis may be at increased risk and should be closely monitored while taking birth-control pills. Women with current or previous benign or malignant hepatic tumors should not take oral contraceptives. Active hepatitis is an absolute contraindication to using birth control pills, although patients with a past history of hepatitis and no evidence of active disease can have a trial of these drugs with close follow-up. A final group of women who should avoid oral contraceptives is those with familial defects of biliary excretion, including the Dubin-Johnson syndrome, Rotor's syndrome, and benign intrahepatic recurrent cholestasis. Dubin-Johnson syndrome is often asymptomatic and may manifest only during pregnancy or during the use of oral contraceptives. The reduction in hepatic excretory function induced by the sex steroids can transform the mild hyperbilirubinemia into frank jaundice. Oral contraceptive agents are the most widely used reversible means of birth control currently available. Fortunately, the complications associated with these drugs are infrequent and may be decreasing due to lower-dose products. Complications still occur, however, and need to be recognized by the general internist as medication-induced problems so the offending drugs can be discontinued and appropriate treatment and follow-up initiated. In addition, patients at risk for the development of complications need to be recognized and advised prior to the introduction of oral contraceptives.

Adolescent

[Oral contraceptives: undesirable effects in internal medicine].

Eight instructive clinical case reports on younger women demonstrate the actual problem of severe adverse reactions (ADR) associated with oral contraceptives. Complications consisted of cerebral arterial thrombosis, peripheral arterial thrombosis, cerebral embolism, pelvic vein thrombosis, pulmonary embolism, thrombosis of the sinus sagittalis, recurrent pancreatitis and focal nodular hyperplasia of the liver. Contraindications of hormonal contraception (i.e. heavy smoking) were not always taken seriously by the prescribing physician. The data bank of the Medicines Commission of the German Medical Association contributed 648 cases to draw an ADR frequency profile, according to age, doses, duration of prescription and deaths. 25 deaths in close connection to oral contraception intake were reported, mostly caused by arterial or venous thromboembolism. Deaths predominantly were reported in women less than or equal to 30 years old, mostly following exposition to low-dose-preparations and after relatively short duration of intake (less than or equal to 3 years). These non-representative observations call for strict consideration of contraindications and use of low-dose-preparations, even in younger women.

Adult

Effect of pregnancy on liver tumor associated with oral contraceptives.

Four cases of liver adenoma associated with oral contraceptives complicating pregnancy are reported. All patients were symptomatic during pregnancy and 2 were admitted with rupture of the adenoma. One subsequently died. Increased growth and vascularity of adenomas during pregnancy is highly likely. The potential for development of lethal complications is considerable.

Adenoma

Cardiovascular death among women under 40 years of age using low-estrogen oral contraceptives and intrauterine devices in Finland from 1975 to 1984.

From 1975 to 1984, there were 1,585,000 women-years of oral contraceptive use and 1,975,000 women-years of copper-bearing intrauterine device use in Finland. During this 10-year period, 20 women between 15 and 39 years of age died of pulmonary embolism, 41 of coronary heart disease, and 311 of intracranial hemorrhage. The diagnoses were confirmed in 89% at necropsy examination. The contraceptive method used by patients was determined in 84% by means of inquiry sent to family planning clinics. Among the 20 patients who died of pulmonary embolism, four died while taking the pill, which gives a relative risk of 1.2 (95% confidence limits, 0.37 to 3.62; p = 0.78). The corresponding values for death from myocardial infarction and intracranial hemorrhage were 0.19 (95% confidence limits, 0.05 to 0.70; p = 0.01) and 0.36 (95% confidence limits, 0.18 to 0.70; p = 0.03), respectively. None among the copper intrauterine device users under the age of 40 years died of pulmonary embolism during 1,383,000 women-years of intrauterine device use. The relative risk of death from intracranial hemorrhage among intrauterine device users was 1.18 (95% confidence limits, 0.70 to 1.99, p = 0.25).

Adolescent

Oral contraceptives and skin neoplasia.

A possible association between oral contraception and the development of cutaneous melanoma has been raised largely because of the hyperpigmentation of pregnancy and the effect pregnancy may have on the outcome of established disease. Present evidence suggests there is no causal link between oral contraceptive (OC) use and melanoma (or with benign melanocytic nevi), nor has a specific subgroup of women or subtype of melanoma been consistently implicated as being at increased risk of this disease due to use of OCs.

Age Factors

Use of echosonography to monitor uterine placement of intrauterine devices after immediate postpartum insertions.

A study designed to monitor uterine placement of IUDs inserted immediately postpartum using echosonography was conducted at the Hospital de Gineco Obstetricia No. 23, "Dr. Ignacio Morones Prieto" in Monterrey, Mexico. TCu220 and Delta T IUDs were randomly assigned to, and inserted in women immediately following a normal vaginal delivery. Ultrasound examinations were to be performed within 60 min postinsertion, at 24 h postinsertion and at 1- and 3-month follow-up visits. There were no differences in the expulsion rates of the two device groups. Data are presented on the readings taken at the ultrasound examinations of the distance between the fundus and the upper part of the stem of the T. These differences differed significantly between the two device groups at the first ultrasound reading only (P less than or equal to 0.01). No relationship was found between the incidence of expulsion and the distance between the IUD and the fundus at any of the readings.

Female

Is persistent pelvic pain and pelvic joint instability associated with early menarche and with oral contraceptives?

A study of 153 women with persistent pelvic pain and pelvic joint instability (PPPJI) following parturition, revealed that the women differed from the controls by a significantly lower age at menarche. Precocious puberty is associated with a fibrous dysplasia which resembles that seen in some PPPJI women patients at operations. Precocious puberty is known to be associated with hypothalamic dysfunction. Following cessation of lactation, 70 of 153 women did suffer galactorrhea and breast discomfort, suggesting a possible affection of the hypothalamic-pituitary system. Age at menarche was higher in users of oral contraceptives (OC) than in non-users, but onset of PPPJI was significantly earlier by gestation, and galactorrhea, and breast discomfort more frequent (60% affected as compared to 30% of non-users), suggesting that use of OC affects the hypothalamus in a manner similar to that associated with very early puberty. The widespread use of contraceptives is important if it truly leads to an increased proportion of PPPJI among reproducing women. Onset of puberty, controlled by the hypothalamus, coincides with the final step in brain development--elimination of some 40% of neuronal synapses. Age at puberty has declined by some 4 years in 100 years, and it is still falling. It cannot be excluded that in some very early maturers, redundancy of neuronal synapses persists, and that this is associated with hypothalamic dysfunction.

Adult

Geographic tongue during a year of oral contraceptive cycles.

The geographic tongue of a 23-year-old female student was examined daily for one year. The size, number and location of the lesions were recorded using transparent films. The phase of the oral contraceptive cycle appeared to have a marked effect on the initiation and duration of the circinate lesions, the tongue changes being severest on the 17th day of the cycle. There was a positive correlation between the subjective complaint and the clinical picture of the tongue.

Adult

Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases.

The role of antiethinyl estradiol antibodies (anti EE Ab) and associated risk factors was evaluated in 1318 cases of venous or arterial thrombosis in oral contraceptives (OC) users, and compared to 61 non-users and 124 healthy current users. Anti EE Ab were absent in non-users and present in 33% of healthy users and 72% of those with thrombosis, either arterial or venous. Age, duration of use, hyperlipidaemia and smoking were factors associated with thrombosis only in women with an arterial disease. While the two predominant factors, anti EE Ab and smoking may be risk factors in their own right, the combination of both was found in 47.7% of women with thrombosis. It is proposed that thrombosis associated with OC use may be explained by an immunological disease in which anti EE Ab and their complexes with the circulating synthetic hormones may be harmful to the vessels, as also suggested by the type of lesions already described in OC users. The determination of anti EE Ab in healthy users may identify a group at risk of thrombosis.

Adult

[Epidemiology and etiopathogenesis of deep venous thrombosis of the lower limbs].

Deep venous thrombosis and pulmonary embolism are frequent complications of surgery. A careful evaluation of both the thromboembolic and the haemorrhagic risks depends on the type of intervention and associated individual risk factors. Such an evaluation should allow allocating the patient to an appropriate prevention which consists of mechanical and/or pharmacological means.

Age Factors

Clinical significance of the androgenicity of progestins in hormonal therapy in women.

Optimal efficacy has been achieved in both oral contraception and postmenopausal replacement therapy. The current challenge is to minimize the side effects and metabolic impact of the administered hormones in both oral contraceptives and hormone replacement agents. When the dose of estrogen in oral contraceptives was reduced the risk of thromboembolism decreased, but the androgenic side effects of the progestin became increasingly apparent. The addition of progestins to hormone replacement therapy reduces the risk of endometrial cancer associated with unopposed estrogen, but their androgenicity offsets the favorable effects of estrogen on lipid metabolism. Androgens not only cause troublesome clinical side effects but also induce changes in blood levels of lipoproteins that have been associated with an increased risk of atherogenesis and coronary heart disease, as well as alterations in glucose and insulin levels. Both the side effects and the adverse effects on lipoprotein and glucose metabolism can be reduced by the use of less androgenic progestins.

Contraceptives, Oral

[Sudden death in venous diseases].

We have studied 286 cases of sudden death due to massive pulmonary embolism. In 155 women and 131 men, we made a statistical analysis of the average age, the presence of thrombosis, varices, atherosclerosis, and other complications, and also dietary considerations. We present a detailed observation of a thirty-two year old woman, who died following massive pulmonary embolism, the source of which was thrombosis of the ovarian and pelvic veins. We learned that this woman, who did not smoke, and whose liver was slightly affected, had, for three years, been taking an uninterrupted course of the contraceptive pill Non-Ovlon.

Adult

Contraceptive methods in the McCune-Albright syndrome.

We describe the case of a woman with McCune-Albright syndrome who had a pathological bone fracture while being treated with an oral contraceptive. In this syndrome the bone lesions contain estrogen and progesterone receptors. The possibility of progression of the bone lesions during pregnancy is well-known. We judge the use of oral contraceptives to be dangerous in this syndrome; the affected women must be orientated towards alternative contraceptive methods.

Adult