Applications of heavy isotope tracers to clinical studies: progesterone urinary production rate determination in the menstrual cycle and pregnancy.

A method for the in vivo determination of progesterone production rate using progesterone labeled with deuterium as the tracer and gas chromatography-mass spectrometry for assessing isotope dilution in a urinary metabolite is described. By measuring the ratio of labeled to unlabeled free progesterone in a 24-h urine sample, the problem of identifying a unique metabolite appears to have been avoided. Median progesterone production rates on day 7 of the follicular phase and day 7 of the luteal phase were 3.5 mumol/24 h and 72.6 mumol/24 h, respectively. Where repeated determinations were performed through the luteal phase in two nonconceptual cycles, the familiar midluteal plateau of progesterone production was noted. The MCR of progesterone calculated from luteal phase data was 2051 1/24 h (SD, 275 1/24 h). When determined in pregnancy, progesterone production varied from 250 mumol/24 h at 6 weeks in a singleton pregnancy, to 1565 mumol/24 h at 35 weeks in a triplet pregnancy. Repeated determinations before term in a twin pregnancy detected no evidence of decreasing progesterone production before labor. The value of urinary pregnanediol and plasma progesterone to indirectly monitor progesterone production were confirmed.