Clinical Utilization of Alkaline Phosphatase Measurements

Hormones and the liver. The effect of estrogens, progestins, and pregnancy on hepatic function.

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.

Hepatobiliary complications of oral contraceptives

Hepatic dysfunction induced by contraceptive agents is reviewed and the possible pathogenesis of the distrubance and its clinical implications are discussed. About 40 cases of jaundice attributed to 5 different oral contraceptives have been reported from a variety of countries. Symptoms are generally noticeable within a few weeks of contraceptive use. Cessation of contraceptive therapy usually results in a complete clinical and chemical remisssion within a few weeks to a few months. 13 of the women in whom jaundice due to oral contraceptives was reported to have developed had previously experienced recurrent jaundice or severe pruritus of pregnancy. Abnormalities of other liver functions are more common than the reversible noninflammatory intrahepatic cholestasis. Evidence suggests that postmenopausal women are more frequently and severely affected than premenopausal women. It has recently been demonstrated that norethynodrel and menstranol impair excretion but not conjugation of sulfobromophthalein (BSP) in normal women. A similar effect using high doses of estriol and estradiol has been shown. The available clinical evidence also suggests that the estrogen may be primarily responsible for contraceptive-induced dysfunction. Progestational steroids have been shown to affect liver function; but they usually alter conjugation rather than excretion. It is recommended that women with a history of acute liver disease in the past should be given the contraceptive agents only if there is no evidence of activity. It is concluded that in all women using these agents the onset of pruritus or upper-gastrointentinal-tract symptoms after the first few cycles should suggest the possibility of hepatic dysfunction and appropriate tests should be carried out.

Hepatic Effects of Oral Contraceptives

Two patients had jaundice during treatment with oral contraceptives. One of them had a history of idiopathic jaundice of pregnancy. The laboratory data included elevated levels of serum transaminase and alkaline phosphatase, and increased sulfobromophthalein (Bromsulphthalein) retention. Optical microscopy of the livers revealed intrahepatic cholestasis and slight hepatocellular damage. Electron microscopy showed cholestasis and hepato-cellular damage. Similar cases have been reported in the literature.

Jaundice during treatment with oral contraceptive agents: report of two cases.

The effects of oral contraceptives (OCs) on liver function were stud ied in 243 women over a period of 6-18 months. The subjects received a combined regimen of 2 mg norethindrone and .075 mg mestranol. Liver function tests revealed abnormally elevated levels of bromosulphthalein retention in 42% of the cases of thymol turbidity in 11% of SGPT in 7% of SGOT in 6% and of alkaline phosphatase in 2% of the cases. 1 patient developed jaundice after 11 months of use though the condition subsided within 4 days even though medication was continued. The results suggest that the compound used in this study may be hepatotoxic.

https://www.bmj.com/content/bmj/1/5447/1414.full.pdf

Ulf Larsson-Cohn

Papers

Oral contraception and liver-function tests.