Jaundice Associated with Norethindrone Acetate Therapy

Perez-Mera, Rafael A. Captain; Shields, Charles E.

doi:10.1056/nejm196211292672208

Cited by 26 publications

(5 citation statements)

References 8 publications

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“…The association between oral estrogen-containing preparations and several cholestatic syndromes has been well recognised since 1962 [1] ; and of the canalicular type with little portal inflammation. It is thought that these reactions are because of the estrogen component; hence it is widely used as an experimental model of hepatocellular cholestasis.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged cholestasis following successful removal of common bile duct stones: Beware patients on estrogen therapy

Dunn¹,

McNair²

2007

WJG

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of the fetus or drug withdrawal leads to improvement of liver function. This tends to occur over several weeks or months [3] . It has been shown in observational studies that estrogen therapy is an important risk factor for gallbladder disease [4] . A recent randomized double-blind placebocontrolled trial of otherwise healthy postmenopausal women has demonstrated that the risk of adverse biliary tract outcomes, such as cholecystitis, is substantially increased by exogenous estrogen therapy [5] . Estrogens are thought to promote gallstone formation by significantly elevating the biliary cholesterol saturation index and a reduction of the nucleation time [6] . We present two cases of prolonged cholestasis after removal of obstructing common bile duct (CBD) stones at endoscopic retrograde cholangiopancreatography (ERCP). CASE REPORTS Case 1A 25-year-old Caucasian woman presented at 6 wk post partum with pruritus and right upper quadrant pain. There was no jaundice evident, and she had been asymptomatic throughout her pregnancy. She had stopped taking Microgynon (ethinlyestradiol 30 μg and levonorgestrel 150 μg) 1 year previously. Her mother had undergone cholecystectomy aged 50 years. Physical examination was unremarkable, and liver function tests showed a total serum bilirubin level of 43 μmol/L, alanine aminotransferase (ALT) 187 IU/L, alkaline phosphatase (ALP) 81 IU/L and gamma-glutamyltranspeptidase (γ-GT) 88 IU/L (Figure 1). Liver ultrasound scan showed multiple calculi in the gall bladder and a CBD of 6 mm, with no evidence of intraductal stones.She presented again 6 wk later with worsening pruritus, biliary colic and jaundice. The patient had restarted Microgynon in the interim period. She denied exposure to alcohol or illegal drugs. There were no risk factors for viral hepatitis. Her weight had dropped by 8 kg and she had icterus. Abdominal palpation revealed a tender right upper quadrant but no hepatosplenomegaly. Retesting of liver biochemistry showed a total serum bilirubin level of 163 μmol/L and a twofold increase in serum ALP. ALT remained elevated at 163 IU/L. Abdominal ultrasound scanning showed a thick-walled edematous gallbladder with multiple small calculi, one impacted in the neck of the gallbladder. The CBD measured 3.5 mm.Endoscopic retrograde cholangiopancreatography (ERCP) was perfor med and revealed two calculi in the CBD, the larg est measuring 5 mm. A 12-mm AbstractThere are various well described forms of chronic cholestatic jaundice in adults, such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic cholestasis of pregnancy. We present two cases of prolonged cholestasis following removal of gallstones at endoscopic retrograde cholangiopancreatography (ERCP) and subsequent clear cholangiography. Both patients were taking oral estrogens at the time of presentation, which were subsequently withdrawn. The first case responded rapidly to corticosteroid treatment, and the second case had a much slower resolution with ursodeoxycholic acid. Both cases highlighted the signific...

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Section: Discussionmentioning

confidence: 99%

“…Estrogens have been a well-recognized cause of cholestatic jaundice since 1962 [1] , and are commonly used in an experimental model of hepatocellular cholestasis. The similarity between such drug reactions and the syndrome of intrahepatic cholestasis of pregnancy has been reported [2] .…”

Section: Introductionmentioning

confidence: 99%

Prolonged cholestasis following successful removal of common bile duct stones: Beware patients on estrogen therapy

Dunn¹,

McNair²

2007

WJG

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show abstract

“…In the original twelve patients of Eisalo et al (1964) lynoestrenol was inactive, and Borglin (1965) had similar results. In other studies, however, the 19norprogestagens without oestrogens have been shown to impair liver function and rarely to cause jaundice (Perez-Mera & Shields, 1962). In a recent report, remarkably prolonged and deep jaundice developed in two sisters, one treated with norethisterone alone, the other with norethisterone plus ethynyloestradiol (Somayaji et al, 1968).…”

Section: Progestagensmentioning

confidence: 92%

Developments in jaundice

Thompson¹,

Williams²

1969

Postgraduate Medical Journal

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“…There are case reports that NEA at a dose of ≥10 mg daily is associated with the development of a hepatic adenoma, 6 elevated liver transaminase concentration, 7 and jaundice. 8 If NEA 5 mg daily is not effective in controlling pelvic pain caused by endometriosis, I stop the NEA and start a GnRH analogue, most often elagolix.…”

Section: When Plan a Is Not Working Move Expeditiously To Plan Bmentioning

confidence: 99%