[Decrease in anticoagulant factors in patients with prostate cancer treated with diethylstilbestrol diphosphate].
OBJECTIVE
Estrogen has been highly evaluated as one of the most potent endocrine agents for the treatment of prostate cancer. Unfortunately, a high risk of cardiovascular complications is a clinically important adverse effect of estrogen therapy, and occasionally the complications are fatal. In recent years a high incidence (55%) of thrombotic events has been reported in patients with congenital protein S (PS) deficiency. The aim of this study is to determine the relationship between cardiovascular complications of estrogen therapy and anticoagulant factor levels in the serum of patients with prostate cancer.


METHODS
Study 1 employed 99 patients with prostate cancer: 39 were untreated, 25 were treated with LH-RH agonist therapy alone, and 35 were treated with oral diethylstilbestrol diphosphate (DESdP) 300 mg per day. We measured the serum levels of anticoagulant factors, parameters antithrombin III (ATIII), protein C (PC), PS, coagulant and fibrinolytic factors in all patients. In study 2, the adverse effects of DESdP therapy on the serum levels of anticoagulant factors were examined in 8 patients with advanced prostate cancer.


RESULTS
In study 1, the ATIII and PS levels of the patients treated with estrogen therapy were significantly lower than those in either the untreated patients or the patients treated with an LHRH agonist alone. Especially, both PS antigen (51.5 +/- 16.0%) and PS activity (42.9 +/- 16.0%) were markedly lower in estrogen-treated patients than in the untreated patients (102 +/- 20.8%, 100.6 +/- 20.7%, respectively) or the patients treated with an LH-RH agonist alone (97.9 +/- 16.8%, 91.5 +/- 17.7%, respectively, both p < 0.0001). PS was decreased to below the normal lower limit of normal in 82% (24/35) of the patients on estrogen therapy. In study 2, all 8 cases showed a significant decrease in PS after DESdP therapy.


CONCLUSIONS
Our results showed that the PS levels in the oral DESdP group were almost the same as in patients with congenital PS deficiency. We conclude that decreased PS may play a role in the development of cardiovascular complications in prostate cancer patients on estrogen therapy.
Hayashi
Norihiro
N
Department of Urology, Jikei University School of Medicine.
Wada
Tetsuro
T
Ikemoto
Isao
I
Oishi
Yukihiko
Y
Suzuki
Hidenori
H
Ueda
Masataka
M
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000990:Antithrombin III / Q000032:analysis*; D004054:Diethylstilbestrol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis
D018931:Antineoplastic Agents, Hormonal; D011486:Protein C; D017293:Protein S; D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol; D000990:Antithrombin III; C004955:fosfestrol