Fig. 4.

DOX suppresses exogenous 17β-estradiol- and progesterone-induced estrous cycle stimulation in ovariectomized SHRs. a Representative line graph depiction of the estrous cycle before any treatment for 3 days, after implantation at days 3 to 6 prior to DOX treatment, and post DOX treatment at days 3 to 8. Animals were implanted with time-release pellets that contain a control matrix (vehicle), 17β-estradiol (E2), progesterone (P4), tamoxifen (Tam), and combination treatments of E2 + Tam, and E2+ P4. DOX was administered 6 days following implantation. The estrous stages were determined by vaginal cytology in at least three animals per stage and treatment. Red arrow indicates implantation date and DOX treatment, respectively. b, c SST-2 tumor volume and weight of ovariectomized SHRs implanted with the time-release pellets at day 12 of a single saline, or DOX treatment (n = 6–7 per implant group per treatment). The bars represent the mean ± SEM. Two-way ANOVA results are displayed in Additional file 2: Table S3. *p < 0.05 according to Tukey’s multiple comparison between implants and treatment