Clinical Cancer Research, Vol 2, Issue 9 1515-1521, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Profound suppression of plasma estrogens by megestrol acetate in postmenopausal breast cancer patients

S Lundgren, SI Helle and PE Lonning
Department of Oncology, Trondheim University Hospital, 7006 Trondheim, and Department of Oncology, Haukeland Hospital, University of Bergen, N-5021 Bergen, Norway.

Twelve postmenopausal women suffering from advanced breast cancer had plasma estrogens, androgens, cortisol, and gonadotropins determined before therapy and during treatment with megestrol acetate (MA) in oral doses escalated from 40 to 160 mg. The plasma clearance and production rate of estrone and estrone sulfate were determined before treatment and after 4 weeks of therapy with 160 mg MA. Treatment with MA suppressed plasma levels of dehydroepiandrosterone sulfate, androstenedione, and cortisol in a dose-dependent manner to <10% of pretreatment values. Plasma testosterone, estradiol, estrone, and estrone sulfate were suppressed to 18-29% of pretreatment values, whereas the gonadotropins were suppressed to 35-52%. The plasma clearance rates of estrone and estrone sulfate were increased by a mean value of 23.7% (P < 0.01) and 23.5% (P < 0.025), whereas the production rates were reduced by 76.7% (P < 0.0005) and 76.1% (P < 0.0005), respectively. Our findings indicate that MA causes profound suppression of adrenal steroid production but in addition suppresses ovarian secretion of androgens in postmenopausal breast cancer patients. The reduction in plasma estrogens is comparable to values obtained with commonly used aromatase inhibitors and may be responsible for its antitumor effects in breast cancer.

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