Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Adlercreutz, Herman; Martin, Finian; Tikkanen, Matti J.; Pulkkinen, M.O.

doi:10.1530/acta.0.0800551

Cited by 41 publications

(14 citation statements)

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“…This contrasts to the patterns of the other "neutral" steroid hormones (50). Changes in metabolism of natural estrogens after application of ampicillin have been explained by interference with the enterohepatic circulation of estrogens (51). Recent animal studies (52) are supportive of this view: the antibiotic neomycin, when orally applied to rats, markedly inhibits enterohepatic recirculation of metabolites of estradiol and mestranol by directly affecting the gut microflora which is responsible for deconjugation of the biliary steroid conjugates.…”

Section: Effect Ofdrugs On Enterohepatic Circulation Of Esgensmentioning

confidence: 99%

Interactions between clinically used drugs and oral contraceptives.

Bolt

1994

Environ Health Perspect

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Metabolism of contraceptive compounds may be influenced by various drugs. Of clinical importance is induction by barbiturates, by diphenylhydantoin, and especially by rifampicin, of enzymes that are responsible for degradation of estrogens. The major target is the hepatic microsomal estrogen-2-hydroxylase (cytochrome P450 3A4). Another type of interaction of drugs with disposition and effectiveness of estrogens is impairment of their enterohepatic circulation. This may be due to absorption of biliary estrogen conjugates (e.g., by cholestyramine) or to insufficient cleavage of the conjugate by intestinal bacteria, the latter being observed after administration of antibiotics (e.g., ampicillin, neomycin). -Environ Health Perspect 102(Suppl 9): 35-38 (1994)

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Section: Effect Ofdrugs On Enterohepatic Circulation Of Esgensmentioning

confidence: 99%

Interactions between clinically used drugs and oral contraceptives.

Bolt

1994

Environ Health Perspect

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“…Antibiotics have been used by a number of investigators when studying the role of the intestinal microflora in steroid metabolism (9)(10)(11)(12)(13)(14)(15). Engel (16) showed that the administration of antibiotics to a human subject reduced the excretion of administered radioactive E 2 in urine, and, in this laboratory, it was recently shown that ampicillin administration to pregnant women, while causing reduced urinary E 3 , 16a-OHE!, 16/3-OHE l5 16-oxoE 2 and 15a-OHEi excretion (17), induced large increases in fecal concentrations of unconjugated and conjugated E 3 (15). In this study, a more exhaustive investigation of the effects of ampicillin on the fecal excretion of estrogens in pregnancy was undertaken by measuring the concentrations of 12 endogenous estrogens.…”

mentioning

confidence: 99%

Intestinal Metabolism of Estrogens1

Adlercreutz

Martin

Pulkkinen

et al. 1976

The Journal of Clinical Endocrinology & Metabolism

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147

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Estrogen metabolism in the human intestine was studied in two ways. Firstly, by measuring the excretion of 12 estrogens in pooled human late pregnancy feces before and during the administration of ampicillin (2 g/day). Secondly, by administering 5.4 and 20 mg of 16alpha-hydroxyestrone orally to two postmenopausal women and analyzing the estrogens in simultaneously drawn portal and peripheral venous blood samples at time intervals from 0 to 150 min after steroid administration. The majority of the estrogens in normal pregnancy feces were unconjugated. The amounts of estradiol, estreon and 16-epiestriol excreted, relative to the principal estrogen estriol, were greater than in pregnancy bile or urine and 16alpha-hydroxyestrone, an important biliary estrogen, was only present in trace amounts. Considerable quantities of 15alpha-hydroxyestradiol-17beta were also found. Ampicillin administration, which decreases intestinal bacterial steroid metabolism, caused a huge increase in the fecal excretion of conjugated estrogens. In particular it caused very striking increases in the excretion of both unconjugated and conjugated, estriol, 15alpha-hydroxyestrone, 15alpha-hydroxyestradiol and 2-methoxyestrone. These findings emphasize the active role played by the intestinal microflora in estrogen metabolism under normal conditions. Administration of 16alpha-hydroxyestrone resulted in increases in portal venous unconjugated and conjugated 16alpha-hydroxyestrone, 16-oxoestradiol-17beta, 15alpha-hydroxyestrone, 16-epiestriol and conjugated estriol levels. The most significant finding in both subjects was the large increase in portal venous unconjugated 15alpha-hydroxyestrone. This would suggest that the human intestine (or intestinal contents) has the ability to carry out the transformation, 16alpha-hydroxyestrone leads to 15alpha-hydroxyestrone. Increases in the same estrogens were found in peripheral plasma, with the increase in conjugated estriol occurring in peripheral blood before it was seen in portal blood. The largest elevations in peripheral plasma values were seen in unconjugated estriol and conjugated 16alpha-hydroxyestrone in the subject who received the 20 mg dose and in unconjugated 16alpha-hydroxyestrone and 16-oxoestradiol-17beta in the subject who had the 5.4 mg dose. The intestinal and enterohepatic metabolism of estrogens is discussed in relation to these findings.

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“…The NCE variable decreased significantly from 10.5 to 4.8 nmol/1 (p < 0.003). Mixed cord serum levels were for TE 2,985 (2,825) nmol/1, NCE 97.7 (75.9-125.7) nmol/1, and CA 0.70 (0.35-1.39) nmol/1.…”

Section: Resultsmentioning

confidence: 95%

“…For instance, resorp tion of cholic acid from the intestine takes place in the distal ileum [19], Estriol is taken up by cells in the colon [20]. The factors that govern these processes have not been studied in detail, but it is clear that food ingestion is a major factor in CA resorption [19], whereas ampicillin may prohibit estriol uptake from the intestine [2,5,8,17,21], A difference between maternal serum and cord arterial and venous serum concentra tions of CA were reported by Laatikainen [14] in 1977, who found higher levels in cord serum. This result is different from our find ings showing similar levels in mixed umbili cal serum and maternal serum.…”

Section: Discussionmentioning

confidence: 99%

Estriol and Cholic Acid in Maternal Serum in Induced Labor

Bremme¹,

Eneroth²,

Samuelson³

1984

Gynecol Obstet Invest

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Prostaglandin E₂ (PGE₂), but not oxytocin, treatment to induce parturition brought about an increase (p < 0.001) in maternal serum levels of total estrogens (conjugated and nonconjugated estriol). There was no increase in nonconjugated estriol. To explore if the changes were related to an altered enterohepatic circulation, cholic acid assay in maternal serum was used. There were no changes in cholic acid which parallelled those in total estrogens. It is concluded that PGE₂ does not appear to affect enterohepatic circulation of steroids, and it is suggested that the increase in total estrogens may be caused by changes in the kidney excretion of estriol.

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Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Cited by 41 publications

References 4 publications

Interactions between clinically used drugs and oral contraceptives.

Interactions between clinically used drugs and oral contraceptives.

Intestinal Metabolism of Estrogens1

Estriol and Cholic Acid in Maternal Serum in Induced Labor

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