Inactivation of contraceptive steroid hormones by human intestinal clostridia

Abstract

Steroid hormones reduced in ring-A are devoid of hormonal activity. In metabolic experiments we found that human fecal flora reduced the Δ4-3-keto structure of natural progestins to 3α-hydroxy, 5β-steroid metabolites (3α,5β) and of synthetic progestins to a mixture of 3α,5β and 3β,5β compounds. 3α,5β-Reductase was synthesized by Clostridium paraputrificum and had a strong affinity for natural progestins such as progesterone. 3β,5β-Reductase was synthesized by Clostridium innocuum and had a stronger affinity for synthetic progestins. A third enzyme, 3β,5α-reductase, was synthesized by St. Luke's strain 209 (Clostridium species 'J-1') but was only observed when pure cultures were used. Ring-A reduction of synthetic progestins was 3 to 10 times slower than that of natural progestins, thus explaining the pharmacological superiority of synthetic progestins over naturally occurring analogs.