Abstract
We hypothesized that megestrol acetate (MA) may work on breast carcinoma by inducing changes in serum sex steroid levels. We prospectively measured levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) in 18 postmenopausal women before and during megestrol acetate therapy. MA significantly suppressed serum FSH, LH, DHEA and E1 levels. However, this was accompanied by a marked increase in serum E2 levels as measured by radioimmunoassay performed on whole serum. MA did not cross-react with the anti-E2 antibodies used in the assay. Elevated E2 levels also occurred in oophorectomized and/or adrenalectomized patients indicating the ovary and adrenal are not the source of the elevated E2 levels. We conclude that MA may be metabolized to oestrogenic compounds that crossreact with antibodies to E2, explaining the elevated E2 levels observed. The effects of these oestrogenic metabolites on breast carcinoma are unknown.
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