• prostate carcinoma;
  • estradiol;
  • estrogen;
  • hormonal therapy;
  • transdermal



Oral estrogen therapy has activity in patients with hormone-naive and androgen-independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids “first pass” liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC.


Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24-hour patches replaced every 7 days). Serum prostate-specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals.


Three of 24 patients (12.5%; 95% confidence interval [CI], 0–26%) had a confirmed PSA reduction > 50%. The Kaplan–Meier estimate of median time to disease progression was 12 weeks (95% CI, 4.6–19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (±95% CI) serum estradiol level increased from 17.2 pg.mL (range, 14.8–19.6 pg/mL) to 460.7 pg/mL (range, 334.6–586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed.


In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors. Cancer 2005. © 2005 American Cancer Society.