The effect of chlormadinone acetate on progesterone secretion and metabolism.

Abstract

ABSTRACT The effect of chlormadinone acetate (6-chloro-17α-hydroxypregna-4,6-diene-3,20-dione-17-acetate) on the secretion and metabolism of progesterone has been investigated in six healthy women. Twenty-four hour urine samples were collected daily throughout pre-treatment cycles and again throughout the second cycle of treatment with 0.5 mg/day chlormadinone acetate. In all urine specimens LH, pregnanediol, oestrone, 17β-oestradiol, and oestriol were determined. Progesterone metabolism was assessed in terms of the transformation of labelled progesterone administered intravenously nine days after the urinary LH peak and progesterone production was calculated from the conversion of labelled hormone to urinary 5β-pregnane-3α,20α-diol glucuroniside and the mass of urinary metabolite of endogenous origin. The results suggested that although the LH peak was markedly suppressed in all subjects (P 0.05 – 0.02; t test), the ovarian response could be divided into two categories. In three individuals, a low but definite premenstrual rise in LH excretion persisted and this was associated with normal or only moderately suppressed progesterone production rates. In addition, there was only a minimal decrease in the level of pregnanediol during the luteal phase of the cycle and in the cyclical excretion of urinary oestrogens. These results are consistent with the luteinisation of a developing follicle without ovulation having necessarily occurred. In the remaining three subjects, the premenstrual rise in LH was not detectable and progesterone production was markedly suppressed. There was no evidence of a rise in pregnanediol in the second half of the cycle in two patients and in the third the level was markedly reduced. In addition, in two of those cycles there was suppression of urinary oestrogen excretion. In treated cycles, there was a significantly lower incorporation of radioactivity into products liberated by solvolysis (P 0.02–0.01; t test). Furthermore, in subjects in whom the progesterone production rate was not markedly suppressed, there was a significant decrease in the conversion of administered progesterone to 5β-pregnane-3α,20α-diol (P 0.01–0.001; t test) and some increase in the conversion to 5α-pregnan-3α-ol-20-one (P 0.02–0.01;t test).