PROGESTIN TREATMENT IN THE DOG .2. EFFECTS ON THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS

The effects of two synthetic progestins, medroxyprogesterone acetate ( MPA) and proligestone (PROL), on the hypothalamic-pituitary-adrenocort ical (HPA) axis were studied in two groups of eight ovariohysterectomi zed dogs each. Eight injections of long-acting progestins were adminis tered at 3-week intervals. Recovery of the HPA axis was studied in fou r dogs of each group in the following 6 months. Basal levels of adreno corticotrophin (ACTH) and cortisol in plasma and the urinary corticoid /creatinine ratio were measured. The responsiveness of the HPA axis wa s investigated by stimulation with ovine corticotrophin-releasing horm one. Both MPA and PROL caused sawtooth patterns of supression of basal ACTH and cortisol levels in plasma, synchronous with the time of admi nistration. The suppression of the adrenocortical component of the HPA axis was most pronounced. Adrenocorticotrophin production also was af fected but to a lesser extent and occurred especially in PROL-treated dogs. Soon after the cessation of progestin administration ACTH levels increased, sometimes with a rebound. In both groups basal cortisol le vels and urinary corticoid/creatinine ratios did not return to pretrea tment levels until 6 months after the last progestin injection. It is concluded that MPA and PROL act as glucocorticoid agonists and suppres s the HPA axis. The suppression at the adrenocortical level may last f or 6 months.