Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature

Abstract

Sporadic single case reports linking glucocorticoidlike activity to megestrol acetate have been reported in the literature. These findings have important implications for patient care. Adverse drug experience reports to the US Food and Drug Administration from 1984 through 1996 and a MEDLINE search of the literature from 1984 through 1996 provided the case reports. Five cases of Cushing syndrome, 12 cases of new-onset diabetes, and 16 cases of adrenal insufficiency were identified in association with megestrol therapy. Twelve cases in which preexisting diabetes was exacerbated and 17 cases of possible adrenal insufficiency were identified. Therapy with megestrol can result in clinical manifestations of glucocorticoidlike activity, including Cushing syndrome, diabetes, and adrenal insufficiency. Clinicians need to be aware of this association as these complications can be life-threatening if not recognized.

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study

“…Megestrol acetate has glucocorticoid activity, and high doses or a prolonged treatment period with megestrol acetate reduce plasma ACTH and cortisol secretion, leading to adrenal insufficiency secondary to prolonged suppression of the hypothalamic-pituitary-adrenal axis [24][25][26][27]. In both the pilot and this study, megestrol acetate treatment was significantly associated with adrenal suppression on antiemetic dexamethasone therapy.…”

Differential diagnostics of adrenal incedentaloma

“…В частности, часто не учитывают кожные крема (включаю щие отбеливающие агенты), травяные лекар ства, "тоники", внутрисуставные и невраль ные инъекции. Мегестрол (медроксипрогес терона ацетат) является синтетическим про изводным прогестерона, у которого выраже на глюкокортикоидная активность, и в высо ких дозах препарат может вызвать ятроген ный синдром Кушинга [21]. Несоблюдение рекомендаций приводит к неоправданным исследованиям, ложным выводам, отсут ствию прагматического эффекта.…”

Unusual causes of Cushing's syndrome

“…As already discussed, increased sensitivity to glucocorticoids could be the underlying mechanism in these unusual cases. Megestrol acetate, a progestational pharmaceutical compound used in the treatment of advanced breast and endometrial cancer and for the cachexia and wasting associated with HIV infection has also been shown to cause Cushing's syndrome (55). Glucocorticoid-like effects are seen in up to 30% of patients treated for periods longer than 6 weeks.…”