Tumor incidence, mammary gland alterations and body weight curves in MPA-treated mice. (a) Mammary tumor incidence. C57BL/6 mice were implanted with 40 mg MPA pellets that were replaced 6 months later; historical values of BALB/c using the same protocol were included for comparison. No mammary tumors appeared in MPA-treated or control C57BL/6 mice; control mice were implanted subcutaneously with silastic pellets. (b) Mammary gland alterations in MPA-treated BALB/c and C57BL/6 mice after one year of MPA treatment. The subpanels show the following: (a) a distorted and rotated ductal structure that appears to be forcibly stretched in areas (WM); (b) hyperplasia in the form of irregular paraductal proliferation (WM); (c) atypical ductal side branching showing areas of neoplastic growth (arrows; WM); (d) hematoxylin and eosin showing ductal hyperplasia; (e,f) WM and hematoxylin and eosin pictures showing nearly normal mammary glands of MPA-treated C57BL/6 mice; and (g,h) WM and hematoxylin and eosin pictures of C57BL/6 control mice. (c) Body weight curves of C57BL/6 mice implanted with 40 mg MPA (first arrow) or control blank silastic pellets that were replaced after 6 months (second arrow). All animals were weighed weekly and the results expressed as mean ± standard error. MPA-treated animals showed an increase in body weight that was already evident after the second week of treatment (P < 0.001; two-way ANOVA). ANOVA analysis of variance; MPA, medroxyprogesterone acetate; WM, whole mount.