Estramustine phosphate (EMP), also known as estradiol normustine phosphate and sold under the brand names Emcyt and Estracyt, is a dual estrogen and chemotherapy medication which is used in the treatment of prostate cancer in men. It is taken multiple times a day by mouth or by injection into a vein.

Side effects of EMP include nausea, vomiting, gynecomastia, feminization, demasculinization, sexual dysfunction, blood clots, and cardiovascular complications. EMP is a dual cytostatic and hence chemotherapeutic agent and a hormonal anticancer agent of the estrogen type. It is a prodrug of estramustine and estromustine in terms of its cytostatic effects and a prodrug of estradiol in relation to its estrogenic effects. EMP has strong estrogenic effects at typical clinical dosages, and consequently has marked antigonadotropic and functional antiandrogenic effects.

EMP was introduced for medical use in the early 1970s. It is available in the United States, Canada, the United Kingdom, other European countries, and elsewhere in the world.

EMP is indicated, in the United States, for the palliative treatment of metastatic and/or progressive prostate cancer, whereas in the United Kingdom it is indicated for the treatment of unresponsive or relapsing prostate cancer. The medication is usually reserved for use in hormone-refractory cases of prostate cancer, although it has been used as a first-line monotherapy as well. Response rates with EMP in prostate cancer are said to be equivalent to conventional high-dose estrogen therapy.

Due to its relatively severe side effects and toxicity, EMP has rarely been used in the treatment of prostate cancer. This is especially true in Western countries today. As a result, and also due to the scarce side effects of gonadotropin-releasing hormone modulators (GnRH modulators) like leuprorelin, EMP was almost abandoned. However, encouraging clinical research findings resulted in renewed interest of EMP for the treatment of prostate cancer.

EMP has been used at doses of 140 to 1,400 mg/day orally in the treatment of prostate cancer. However, oral EMP is most commonly used at a dose of 560 to 640 mg/day (280–320 mg twice daily). The recommended dosage of oral EMP in the Food and Drug Administration (FDA) label for Emcyt is 14 mg per kg of body weight (i.e., one 140 mg oral capsule for each 10 kg or 22 lbs of body weight) given in 3 or 4 divided doses per day. The label states that most patients in studies of oral EMP in the United States have received 10 to 16 mg per kg per day. This would be about 900 to 1,440 mg/day for a 90-kg or 200-lb man. Lower doses of oral EMP, such as 280 mg/day, have been found to have comparable effectiveness as higher doses but with improved tolerability and reduced toxicity. Doses of 140 mg/day have been described as a very low dosage. EMP has been used at doses of 240 to 450 mg/day intravenously.

EMP and other estrogens such as polyestradiol phosphate and ethinylestradiol are far less costly than newer therapies such as GnRH modulators, abiraterone acetate, and enzalutamide. In addition, estrogens may offer significant benefits over other means of androgen deprivation therapy, for instance in terms of bone loss and fractures, hot flashes, cognition, and metabolic status.

EMP has been used to prevent the testosterone flare at the start of GnRH agonist therapy in men with prostate cancer.