In 2001, allegations that PC-SPES contained the synthetic estrogendiethylstilbestrol (DES) started to appear on e-mail listservs used by prostate cancer patients and in online newsletters. Prostate cancer patients who were taking PC-SPES noticed that their recent medication was not as effective as the previous batches. A sample of PC-SPES submitted to a testing laboratory by BotanicLab in August 2001 found no DES. BotanicLab posted the letter from the laboratory on their Web site, claiming that PC-SPES contained no DES. However, in other tests of six different lots of PC-SPES received from two different sources in August 2001, Rocky Mountain Instrumental Laboratory found varying amounts of DES in three lots. More tests done by the California Department of Health Services in February 2002 did not find DES but did find warfarin, a prescription drug used as a blood thinner.
The presence of a synthetic estrogen such as DES was suspected early in the clinical use of PC-SPES after reports in the literature discussed the mixture's estrogen-like ability to lower prostate-specific antigen (PSA) levels in AD prostate cancer patients. In addition, the side effects of treatment were similar to those of estrogen therapy.[15,16,17] In one study, patients who showed the most response to PC-SPES were also those who were the most responsive to DES. Reviewed in [11,18] The same study also attempted to find out whether DES or similar compounds were present in PC-SPES. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae using an ethanolic extract of PC-SPES showed estrogenic activity similar to 1nM estradiol. In addition, ovariectomized CD-1 mice showed substantially increased uterine weights. HPLC, gas chromatography, and mass spectrometry did not reveal the presence of DES but rather that of a compound with similar chemical characteristics. The authors of the report concluded that PC-SPES contains estrogenic compounds that are distinct from DES or other synthetic estrogens.
A definitive evaluation of PC-SPES analyzed specific lots of PC-SPES capsules manufactured from 1996 to 2001. In addition to using HPLC to isolate, identify, and quantify the synthetic drugs and active phytoestrogens, this study also identified components using proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis. Tests showed the presence of the synthetic drugs indomethacin (a nonsteroidal anti-inflammatory drug not previously reported in the literature or found in other testing), DES, and warfarin. Testing was also done for concentrations of the two naturally occurring phytosterols, licochalcone A and baicalin. Test results indicated a history of rising and falling levels of contamination by the three synthetic drugs and a recent rise in the naturally occurring phytochemicals in PC-SPES. Lots of PC-SPES manufactured in 1996 through mid-1999 contained indomethacin ranging from 1.07 mg/g to 13.19 mg/g and DES ranging from 107.28 �g/g to 159.27 �g/g and were 2 to 6 times more antineoplastic and up to 50 times more estrogenic than lots manufactured after the spring of 1999. In vitro testing of ethanolic extracts of PC-SPES against LNCaP, PC-3, and DU-145 prostate cancer cell lines showed a decrease in both antineoplasticity and estrogenicity in lots of PC-SPES manufactured in June 1998 through August 2001, which correlated with the amount of DES and indomethacin contamination. Another in vitro test of suspected lots of PC-SPES manufactured from 2000 to 2001 also showed the presence of DES.