Depletion of luteal phase serum progesterone during constant infusion of cortisol phosphate in the cynomolgus monkey

To study the impact of chronic infusions of cortisol phosphate on ovarian function in the cynomolgus monkey. Cortisol phosphate at doses of 5 or 15mg/d or saline were infused for periods of up to 8weeks using subcutaneously implanted osmotic pumps. Animals were maintained in the Center for Experimental Animal Resources, Northwestern University. Serum total and unbound cortisol concentrations, serum total and unbound progesterone (P) concentrations, urinary P metabolites. Mean increases in serum cortisol of 56% and 77% above control levels were achieved. Mean serum P concentrations were not decreased with low-dose cortisol phosphate infusion during the 12days preceding menses, but mean serum P levels were decreased by 69% to 2.3ng/mL during high-dose cortisol phosphate infusion. No corresponding decrease in excretion of conjugated immunoreactive P metabolites was found in daily urine samples during cortisol phosphate infusion, suggesting that production rates of P were unaltered by the cortisol phosphate treatment. Unbound serum cortisol increased by a mean of 162% above control levels during high-dose cortisol phosphate infusion, but no increase occurred in the percentage of unbound serum P. We conclude that elevation of serum cortisol in the range observed in chronically stressed individuals may severely decrease the available P to target organs by displacement of P from plasma proteins but does not inhibit ovarian steroidogenesis or ovulation.