A 59-year-old man was admitted to our hospital because of muscular pain, weakness, and anorexia. He had been treated with 600 mg/day of fosfestrol, a synthetic estrogen, for 10 years for prostatic carcinoma. Endocrinological studies demonstrated adrenocortical insufficiency due to inadequate ACTH secretion. After initiation of glucocorticoid replacement therapy, his symptoms subsided rapidly. To our knowledge, an association between estrogenic agents, including fosfestrol, and secondary adrenocortical insufficiency has not been previously reported. Physicians who treat patients with long-term and high-dose strong estrogenic agents should be cautious about the possible emergence of secondary adrenocortical insufficiency.