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

Objective: To study the impact of chronic infusions of cortisol phosphate on ovarian function in the cynomolgus monkey. Design: Cortisol phosphate at doses of 5 or 15 mg/d or saline were infused for periods of up to 8 weeks using subcutaneously implanted osmotic pumps. Setting: Animals were maintained in the Center for Experimental Animal Resources, Northwestern University. Main Outcome Measures: Serum total and unbound cortisol concentrations, serum total and unbound progesterone (P) concentrations, urinary P metabolites. Results: 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 12 days preceding menses, but mean serum P levels were decreased by 69% to 2.3 ng/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. Conclusions: 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.