To evaluate the in vivo effect of Δ1-testololactone on peripheral aromatization, studies were performed on seven postmenopausal women with metastatic breast cancer. Analysis of variance indicated that there were significant increases of circulating androstenedione (p < 0.05) and estradiol (p < 0.001) during administration of different doses of testololactone. Androstenedione levels were increased with all doses of testololactone tested (50, 100, 250, and 500 mg every 6 hr for 14 days each), while estradiol rose with only the 250- and 500- mg dosages. With administration, there was a significant decrease of estrone (p < 0.001) with the mean level falling from 26 ± 3 (S.E.) to 11 ± 2 pg/ml. The addition of adrenal suppression (dexamethasone, 1 mg nightly at 11 p.m.) significantly lowered androstenedione (p < 0.05) but had no effect on estrone or estradiol levels. Long-term therapy (up to 6 months) with the 250-mg dosage showed continual suppression of estrone with no escape being observed. Studies to determine the reason for the increase of estradiol with testololactone suggested cross-reactivity of the antibody with it in vivo metabolites of the drug. However, these possible metabolites did not bind to uterine cytosol estrogen receptors. The decrease in estrone with testololactone administration presumably explains its antitumor properties.


Presented at the Conference “Aromatase: New Perspectives for Breast Cancer,” December 6 to 9, 1981, Key Biscayne, Fla. This work was supported by USPHS Grant CA23093.

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