Following a single oral dose of 420 mg EMP in men with prostate cancer, maximal levels of estromustine were 310 to 475 ng/mL (475,000 pg/mL) and occurred after 2 to 3 hours. Estradiol levels with 280 mg/day oral EMP have been found to increase to very high concentrations within one week of therapy. In one study, levels of estradiol were over 20,000 pg/mL after 10 days, were about 30,000 pg/mL after 30 days, and peaked at about 40,000 pg/mL at 50 days. Another study found lower estradiol levels of 4,900 to 9,000 pg/mL during chronic therapy with 560 mg/day oral EMP. An additional study found estradiol levels of about 17,000 pg/mL with 140 mg/day oral EMP and 38,000 pg/mL with 280 mg/day oral EMP. The circulating levels of estradiol and estrone during EMP therapy have been reported to exceed normal levels in men by more than 100- and 1,000-fold, respectively. Levels of estramustine and estradiol in the circulation are markedly lower than those of estromustine and estrone, respectively, with a ratio of about 1:10 in both cases. Nonetheless, estradiol levels during EMP therapy appear to be similar to those that occur in mid-to-late pregnancy, which range from 5,000 to 40,000 pg/mL. No unchanged EMP is seen in the circulation with oral administration.