Progestin treatment in the dog. II. Effects on the hypothalamic-pituitary-adrenocortical axis

The effects of two synthetic progestins, medroxyprogesterone acetate (MPA) and proligestone (PROL), on the hypothalamic-pituitary-adrenocortical (HPA) axis were studied in two groups of eight ovariohysterectomized dogs each. Eight injections of long-acting progestins were administered at 3-week intervals. Recovery of the HPA axis was studied in four dogs of each group in the following 6 months. Basal levels of adrenocorticotrophin (ACTH) and cortisol in plasma and the urinary corticoid/creatinine ratio were measured. The responsiveness of the HPA axis was investigated by stimulation with ovine corticotrophin-releasing hormone. Both MPA and PROL caused sawtooth patterns of suppression of basal ACTH and cortisol levels in plasma, synchronous with the time of administration. The suppression of the adrenocortical component of the HPA axis was most pronounced. Adrenocorticotrophin production also was affected 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 levels and urinary corticoid/creatinine ratios did not return to pretreatment levels until 6 months after the last progestin injection. It is concluded that MPA and PROL act as glucocorticoid agonists and suppress the HPA axis. The suppression at the adrenocortical level may last for 6 months.