In order to assess the androgenic activity of
synthetic progestins currently used as "
antiandrogens" for the treatment of
prostate cancer in men, the effect of a series of these compounds has been studied in mice on the growth of the
androgen-sensitive Shionogi
tumor. Female mice (DD/S strain) were inoculated subcutaneously with 10(6) viable cells and divided into groups who received, respectively, the
synthetic "progestins"
medroxyprogesterone acetate (MPA),
megestrol acetate (MEG),
cyproterone acetate (CPA) or
chlormadinone acetate (CMA), compared with the non-steroidal
antiandrogen Flutamide (Flu), each administered at the twice-daily dose of 250 micrograms. Each
synthetic "progestin" exerted a marked stimulatory effect on the growth of the
tumor. The most impressive effect on growth was observed with MPA. In fact, in MPA-treated mice,
tumor size was 17 times larger than control at 4.92 +/- 0.36 cm2/mouse 21 days after inoculation. CPA, CMA and MEG also stimulated the growth of this
androgen-sensitive
tumor, the percentages of stimulation of
tumor size being 3.1-, 3.2- and 11.0-fold above control, respectively, on day 21, while Flu had no significant stimulatory effect. The present data clearly show that all the above-mentioned
progestins have variable levels of stimulatory activity on the growth of the
androgen-sensitive Shionogi
tumor and indicate that such drugs are unlikely to be recommendable for the treatment of
prostate cancer.