The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

Abstract

Summary1. The effect of oestrogens and progestogens and their 17a-ethinyl derivatives on bile flow, maximum rate of bilirubin secretion, serum and liver bilirubin has been studied. 2. Both 17a-ethinyl substituted oestrogens and progestogens greatly reduced the basal bile flow. The parent compounds, oestradiol-17f3 and 19-nortestosterone had little or no effect. 3. A much larger dose of progestogens (40 mg/kg) than oestrogens (5 mg/kg) was needed. 4. Between 12 and 48 h were required for 17a-ethinyloestradiol to produce the effect. 5. Bilirubin maximum secretion rate (Tm) was little affected, the only significant reduction being produced by the 3-methyl ether of 17a-ethinyloestradiol (mestranol). 6. Rises in serum conjugated bilirubin following infusion of bilirubin were produced by 17a-ethinyloestradiol and mestranol but not by the progestogens.

Effect of Combined Oral Contraceptive Pill on Serum Bilirubin and Alkaline Phosphatase

“…21 However, many researchers found increased Alkaline phosphatase levels in OCP users. These results are compatible with Ekhator 20 , KATZ, et al 13 , Hargreaves 23 , Dickerson, et al 15 , and Larsson-Cohn et al 17 . The increased ALP level could be described by cellular degeneration of myocardial, neuronal, and liver cells.…”

“…In this study, serum total bilirubin levels are higher in OCP users in comparison to non-OCP users. This observation coincides with Osifo 13 , KATZ 14 , Dickerson, et al 15 , Rahim et al 16 , and Heikel and Lathe 17 . Larsson Cohn et al 18 observed that serum bilirubin level was within the standard limit after taking OCP.…”

“…The rise in serum bilirubin must be either increased escape from the liver cells, a diminished storage capacity, or reduced transport into bile canaliculi. 17 The effect of OCPs on liver functionality indicated via total bilirubin and direct bilirubin demonstrated that administration of low doses of synthetic OCPs may have the potential for red blood cell destruction in a dose-dependent fashion. 21 Alkaline phosphatase is another liver enzyme that is an indicator of biliary integrity.…”

Estrogen-Induced Cholestasis: Clues to Pathogenesis and Treatment

“…EE administration not only decreases bile salt transport but also decreases the secretory maxima for other organic anions which utilize separate transport pathways. For example, BSP and bilirubin transport maximum are reduced by approximately 50% (21,53,55,58). This generalized defect in organic anion transport suggests a major abnormality in the canalicular membrane; however, no studies have been published which examine hepatic uptake, i.e., sinusoidal membrane integrity.…”

Reversal of Ethinyl Estradiol-induced Bile Secretory Failure with Triton WR-1339

“…The causes(s) of bile secretorv failure (cholestasis) is unknown, but these agents have focused attentioIn oIn abnormalities in the hepatocyte. Ethinyl estradiol, a synthetic estrogen, has been extensively studiedl as a dcrug whiclh produces bile secretory failure characterized by (lecreases in the bile salt independent component of bile flow (2)(3)(4), the maximumti capacity to excrete organic anions such as bile acids (5), bilirubin (6), and bromosulfophthalein (4, 7) and decreased hepatic Na+-K+-ATPase activity (8,9). It has been suggested that this diffuse abnormality in biliary secretory processes is primarily the result of changes in membrane lipid structure (9).…”