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  • Title: Effects of diethylstilbestrol and estramustine phosphate on serum sex hormone binding globulin and testosterone levels in prostate cancer patients.
    Author: Karr JP, Wajsman Z, Kirdani RY, Murphy GP, Sandberg AA.
    Journal: J Urol; 1980 Aug; 124(2):232-6. PubMed ID: 7190620.
    Abstract:
    Serum testosterone-estradiol binding globulin and total testosterone were measured in 2 groups of male controls (less than 50 and more than 65 years old) and in 7 groups of prostatic cancer patients treated with various endocrine manipulation procedures, including orchiectomy, and estramustine phosphate and diethylstibestrol therapy. There were 133 individuals studied. Total serum testosterone levels were significantly higher in the younger versus the older control group and testosterone-estradiol binding globulin levels were significantly higher in the older men. Whereas orchiectomy reduced serum testosterone to low concentrations (72 plus or minus 11 ng. per 100 ml.) testosterone-estradiol binding globulin levels were not altered. In contrast, estramustine phosphate and diethylstilbestrol therapy, when administered to intact or castrated patients, resulted in depressed testosterone and markedly elevated testosterone-estradiol binding globulin serum levels, particularly in those patients receiving estramustine phosphate (less than 35 ng. per 100 ml. and more than 6 micrograms per 100 ml., respectively). These studies led to the conclusion that diethylstilbestrol or estramustine phosphate therapy is significantly more effective than orchiectomy in eliciting a concomitant elevation of testosterone-estradiol binding globulin and a depression of total testosterone. Even though free serum testosterone was not measured in the present study the law of mass action would indicate that in those patients with high testosterone-estradiol binding globulin (more than 5 microgram. per 100 ml.) and low total testosterone levels (less than 80 ng. per 100 ml.) the availability of biologically active (unbound steroid) testosterone would be negligible. This study attempted to determine whether oral administration of diethylstilbestrol (DES) or estramustine phosphate, a mustard compound derivative with unknown mechanism of action, is as effective in the treatment of prostate cancer as castration. Serum testosterone-estradiol binding globulin and total testosterone were measured in 2 groups of male controls (aged under 50 years or over 65 years) and in 7 groups of prostatic cancer patients treated by endocrine manipulation, including orchiectomy and DES or estramustine phosphate. 133 persons were studied. Total serum testosterone levels were significantly higher in younger vs. older controls and testosterone-estradiol binding globulin levels were significantly higher in the older men. Although orchiectomy reduced serum testosterone to low concentrations, the binding globulin level was not altered by surgery. In contrast, estramustine phosphate and DES therapy, administered to intact or castrated patients, led to depressed testosterone and markedly elevated binding globulin levels in serum; this effect was most pronounced among estramustine phosphate users. Therefore, it is concluded that DES or estramustine phosphate therapy is significantly more effective than orchiectomy in eliciting concomitant elevation of the testosterone-estradiol binding globulin and a depression of total testosterone.
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