Steroid Receptors in Megestrol Acetate Therapy

Abstract

The role of megestrol acetate (17α-acetoxy-6-methyl-pregna-4,6-diene-3,20-dione), a synthetic progestin derived from hydroxyprogesterone, in the treatment of advanced breast cancer has long been established: generally, remission can be achieved in ca. 30% of postmenopausal patients [1–3, 12, 13, 16, 18, 19]. It is difficult to define the physiological and pharmacological effects of progesterone and synthetic progestins, since virtually none of them are due exclusively to these hormones. Nevertheless, while estrogens and androgens have mainly growth-stimulating effects, the action of progestins is directed more towards modification and differentiation [14]. Megestrol acetate has been studied in both man and animals and seems to have antiestrogenic, antiandrogenic, and glucocorticoid-like properties [4–8, 10, 15] (Fig. 1). There is little information correlating the effect of megestrol acetate treatment and receptor content in human tumor tissue. Morgan reported response to megestrol acetate in seven of 16 patients with ER+ and in two of five patients with ER- [13]. In our previous study on steroid receptors in megestrol acetate-induced regression of human breast cancer [17], it was demonstrated that megestrol and medroxyprogesterone acetates are strong competitors for steroids which bind specifically to androgen, glucocorticoid, and progesterone receptors, indicating that these progestins are able to bind to these receptors with high affinity. In contrast, they do not compete with estradiol for estrogen receptor binding. Regressions were significantly associated with tumors containing large amounts of androgen receptors, tumors which also generally contain estrogen receptors.

The authors wish to thank Mr. M. S. Henkelman and Mr. H. Portengen for performing the receptor analysis, and Mrs. A. Sugiarsi, Mr. P. van Assendelft, and Mrs. J. L. Wike-Hooley for their assistance