Phase II study of low dose and high dose conjugated estrogen for androgen independent prostate cancer

J Urol. 2007 Jun;177(6):2146-50. doi: 10.1016/j.juro.2007.01.119.


Purpose: Although estrogens have known antitumor activity in androgen independent prostate cancer, the best studied agent, diethylstilbestrol, is no longer commercially available in the United States. We tested 2 doses of the conjugated estrogen Premarin(R) in patients with androgen independent prostate cancer to determine the efficacy and safety of this widely available medication.

Materials and methods: A total of 45 patients with progressive androgen independent prostate cancer were randomly assigned to receive Premarin 1.25 mg once (17) or 3 times (28) daily. Warfarin 1 mg daily was administered to all patients to minimize risk of thromboembolism. Low dose prophylactic breast irradiation was administered to most patients.

Results: Of the patients receiving high dose Premarin 25% achieved a 50% or greater reduction in prostate specific antigen. No patients treated with low dose Premarin reached a 50% reduction in prostate specific antigen. After 3 months of treatment, 11 patients (39.3%) on the high dose arm and 6 patients (35.3%) on the low dose arm showed no signs of progression. Three patients (6.7%) had a thromboembolic event. No significant gynecomastia was noted. A significant difference in dehydroepiandrosterone sulfate levels was detected between those who did and did not respond to Premarin (p = 0.03).

Conclusions: High dose Premarin resulted in prostate specific antigen decreases of 50% or greater in 25% of patients with androgen independent prostate cancer. More than a third of patients receiving high or low dose Premarin maintained stable disease for at least 3 months. With concurrent warfarin 1 mg treatment, 6.7% experienced thromboembolic complications. Premarin 1.25 mg 3 times daily is a reasonable therapeutic option for patients with androgen independent disease.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Estrogens / administration & dosage*
  • Estrogens / adverse effects
  • Estrogens, Conjugated (USP) / administration & dosage*
  • Estrogens, Conjugated (USP) / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Testosterone / blood
  • Treatment Outcome


  • Estrogens
  • Estrogens, Conjugated (USP)
  • Testosterone
  • Prostate-Specific Antigen