INHIBITION OF 3‐BETA‐HYDROXY STEROID DEHYDROGENASE ACTIVITY IN FIRST TRIMESTER HUMAN PREGNANCY WITH TRILOSTANE AND WIN 32729

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Abstract
SUMMARY: The effects of equivalent doses of two inhibitors of the 3‐beta‐hydroxy steroid dehydrogenase enzyme system—WIN 24540 (trilostane) and WIN 32729—on the secretion of progesterone in early human pregnancy are described. Patients and controls less than 12 weeks pregnant were given a single dose of either drug and the resultant hormonal changes monitored for 71/2 h.A consistent fall in plasma progesterone concentrations occurred at all doses and, at the highest dose, they fell to less than 50% of pre‐treatment levels. However, whilst with trilostane the associated increase in plasma concentrations of pregnenolone was always accompanied by a rise in plasma DHA concentrations, with WIN 32729 there appeared to be no adrenal effect at the lower dosage levels.These data demonstrate inhibition of progesterone secretion in human pregnancy using non‐hormonally active steroids. The pattern of steroid precursors indicates that while both drugs inhibit 3‐beta‐hydroxy steroid dehydrogenase activity, WIN 32729 is more selective and only interferes with adrenal steroid biosynthesis at high doses.