The effect of medroxyprogesterone acetate on the pituitary-adrenal axis

Abstract

Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.

PIP: The effects of medroxyprogesterone acetate (MPA), administered im in a total weekly dose of 400, 700, or 1200 mg, on the pituitary-adrenal axis were studied in 12 cancer patients and 1 patient with diabetes mellitus. MPA reduced mean A.M. plasma cortisol concentrations by 76% and mean P.M. cortisol concentrations by 75%. The 24-hour production rate of cortisol was reduced by 67%. 41% of the individual A.M. cortisol determinations and 61% of the individual P.M. determinations were not significantly (p greater than .001) different from 0. Plasma ACTH levels were low throughout treatment, and the response to maximal ACTH stimulation was not pronounced. Evidence of adrenal insufficiency was not observed in any of the patients. The results demonstrate the corticosteroid replacement properties of MPA, and it is suggested that the suppression of adrenal function is most likely mediated by a negative feedback action on the hypothalamus or pituitary.