Effects of antibiotics on oestrogen metabolism.

SIR,-Ampicillin,1 phenoxymethylpenicillin,2 and neomycin3 have been shown to decrease urinary oestriol output in normal human pregnancy. We have explored this matter further by employing a new gas chromatographic method4 which enables the four known urinary oestriol conjugates to be measured separately. Six healthy mothers 33-37 weeks pregnant were given 0 5 g of ampicillin orally four tines daily on three successive days. The mean urinary oestriol output decreased to an average of 69% of the pretreatment level on the second, third, and fourth days after starting the ampicillin treatment. The results indicate that the diminished excretion of one conjugate, oestriol-3-glucuronide, accounted for approximately 90% of this decrease. Oestriol-3-glucuronide is formed in the intestinal mucosal cells5 6 and its formation is dependent on the reabsorption of biliary oestriol in the intestinal tract. Thus ampicillin interferes with the enterohepatic circulation of oestrogens, impairing the synthesis of oestriol-3-glucuronide. The antibiotic probably exerts its effect by changing the composition of the intestinal microflora. It is of interest that another antibiotic, rifampicin, causes contraceptive failures when given to women taking oral contraceptives (Breuer, personal communication). Thus administration of antibiotics may cause unexpected complications through their effect on oestrogen metabolismn.-We are, etc.,