Megestrol acetate therapy and secondary adrenal suppression

Cancer. 1999 Sep 15;86(6):1044-9.


Background: Adrenal suppression has been noted in patients who are receiving medroxyprogesterone acetate (MPA). Megestrol acetate (MA) is used to treat patients with advanced breast carcinoma, cachaexia related to acquired immune deficiency syndrome, and disseminated carcinomatosis, and it is believed to have fewer side effects than MPA. The aim of this study was to test for secondary adrenal suppression in patients receiving MA therapy for advanced metastatic cancer.

Methods: Ten postmenopausal female patients receiving long term MA therapy, nine with advanced metastatic breast carcinoma and one with metastatic ovarian carcinoma, were recruited consecutively from the oncology outpatient clinic at Ninewells Hospital in Dundee, Scotland. A short synacthen test and a corticotrophin-releasing hormone (CRH) stimulation test were performed on two separate occasions. Urine collection for 24-hour urinary free cortisol was performed on 6 patients. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (T4) were measured in eight patients. An insulin stress test (IST) was performed on two patients.

Results: Nine of 10 patients had a poor cortisol response to the short synacthen test. The CRH test had abnormal results in eight of nine patients. In all patients tested, 24-hour urinary free cortisol excretion was low, indicating adrenal suppression. Basal serum FSH, LH, TSH, and free T4 values indicated normal pituitary function. Adrenocorticotrophic hormone response in the CRH test varied and is discussed in this article.

Conclusions: MA causes secondary adrenal suppression that is thought to be due to its effect at the hypothalamic level. The authors recommend a short course of steroid replacement for patients receiving MA at times of acute illness.

MeSH terms

  • Adrenal Glands / drug effects*
  • Adrenocorticotropic Hormone / blood
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Corticotropin-Releasing Hormone
  • Cosyntropin
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / urine
  • Hypoaldosteronism / chemically induced*
  • Hypothalamo-Hypophyseal System / drug effects
  • Megestrol Acetate / adverse effects*
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Pituitary-Adrenal System / drug effects


  • Antineoplastic Agents
  • Cosyntropin
  • adrenocorticotropin zinc
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Megestrol Acetate
  • Hydrocortisone