Abstract
The possibility that medroxyprogesterone acetate (MPA) is clinically effective at least in part by its suppression of adrenal steroidogenesis and a resultant reduction of circulating oestrogen levels was investigated in 49 postmenopausal patients with advanced breast cancer. Thirty-one patients were treated with low dose MPA (100 mg three times daily) and 16 patients with high dose MPA (250 mg four times daily). Plasma levels of androstenedione, testosterone, oestrone and oestradiol were all significantly reduced during treatment, with the suppression being most marked for the 17 beta hydroxysteroids, testosterone and oestradiol. The fall in oestradiol levels was to about 50% of pretreatment levels, but a concomitant fall in SHBG levels to less than 25% of baseline probably resulted in the fall in free, biologically active oestradiol being only to about 70-80% of pretreatment. It is unlikely that this is a major determinant of the activity of MPA in breast cancer.
Highlights
Androstenedione (Dowsett et al, 1984a), testosterone (Sufi et al, 1986), oestradiol and oestrone (Harris et al, 1983) and dehydroepiandrosterone sulphate (Harris et al, 1982) were measured by radioimmunoassay according to previously published methods
Statistical comparisons were performed which confirmed that there were no significant differences in the mean pretreatment levels of the remaining analytes between the treated and untreated patient groups
It has been suggested that in postmenopausal women medroxypregesterone acetate (MPA) may exert at least part of its activity by suppression of adrenal androgen synthesis and the consequent reduction in circulating oestrogens which are derived from the peripheral conversion of these androgens
Summary
Androstenedione (Dowsett et al, 1984a), testosterone (Sufi et al, 1986), oestradiol and oestrone (Harris et al, 1983) and dehydroepiandrosterone sulphate (Harris et al, 1982) were measured by radioimmunoassay according to previously published methods. No significant cross-reaction was found with levels of MPA up to 1 HIg ml- 1 in any of the assays
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