Possible Interaction: Ethinyl Estradiol and S-Adenosylmethionine

“ S-Adenosylmethionine (SAMe) proved to be effective in antagonizing bile secretion impairment induced by a wide range of hepatotoxins, including ethynylestradiol , taurolithocholate, chlorpromazine and alpha-naphthyl-isothiocyanate.”

“In the rechallenge with EE plus SAMe , liver function tests did not differ from basal levels and were significantly lower than the values obtained after EE.”

“Previous investigations have shown that S-adenosyl-L-methionine antagonizes both cholestasis and bile lipid alterations induced by ethynylestradiol in the rat.”

“Since it is still unknown whether S-adenosyl-L-methionine prevents ethynylestradiol-induced cholesterol supersaturation of bile in humans also and how methynation interferes with plasma ethynylestradiol disappearance, the present study has been carried out.”

“These findings indicate that S-adenosyl-L-methionine prevents ethynylestradiol-induced bile lipid changes without interfering with ethynylestradiol kinetics in humans.”

“Prevention by S-adenosyl-L-methionine (SAMe) of the bile flow reduction induced by ethynylestradiol (EE) is demonstrated by comparing the flow rate and the bile salt concentration of bile in EE-treated animals with that in animals given both EE and SAMe.”

“ S-AdenosylL-methionine (SAMe) had no effect on taurocholate uptake or release, but was able to reverse the competitive inhibition induced by ethinylestradiol.”

“The presence of SAMe greatly increased the catabolism of ethinylestradiol by hepatocytes and reduced its covalent binding to hepatocyte macromolecules.”

“This suggests that SAMe may revert the effects of ethinylestradiol of taurocholate uptake by increasing its catabolic rate by hepatocytes.”

“However, EE treatment increased the hepatic contents of SAM and restored the SAM:SAH levels to normal in rats fed diet 2 or 2M.”

“Hepatic Mg2+‐ATPase and y‐glutamyl transpeptidase activities were not affected by SAMe alone but increased when SAMe was given together with EE.”

“Previous investigations demonstrated that S-adenosyl-L-methionine suppresses the cholestatic effect of ethynylestradiol and reduces the irreversible binding of the estrogen to rat liver microsomes, probably favoring ethynylestradiol transformation into its methyl-derivatives.”