Free and protein-bound progesterone during normal and luteal phase defective cycles.

OBJECTIVES: New methods for the measurement of the percent free (%FreeP) and percent corticosteroid binding globulin-bound (%CBG-B) fractions of plasma progesterone (P) are described.
METHODS: Modifications of previously reported equilibrium dialysis and charcoal adsorption assays were used. P binding was analyzed in single midluteal samples of 16 infertile women with endometrial biopsy proven luteal phase defect (LPD) and 10 infertile women with a normal luteal phase.
RESULTS: %FreeP, %CBG-B, percent nonspecific protein-bound P (%NSP), total P and total plasma estradiol (E2) were measured during the normal ovulatory cycles of 5 women. The mean follicular phase %FreeP was found to be lower than in the luteal phase due to a decline in the late follicular phase. This decline correlated with the preovulatory rise in E2. The mean absolute concentration of free P (FreeP) rose significantly in the luteal phase, positively correlating with total P in both phases. Mean %CBG-B and %NSP were unchanged throughout the cycle. P was lower in LPD vs. normal cycles, but %FreeP and %CBG-B were not different. E2 highly correlated with P but not with %FreeP and %CBG-B.
CONCLUSIONS: In normal cycles a small but significant decrease in %FreeP occurs in the late follicular phase and is associated with increasing E2. Changes in total P during the ovulatory cycle reflect changes in the concentration of bioactive P. There were no data to support an association of LPD with changes in the bioactive fraction of P.