Robert S. DiPaola, The New England Journal of Medicine -- September 17, 1998 -- Volume 339, Number 12
Background. Herbal therapies are unconventional treatments in wide use for many diseases. They are sold as nutritional supplements for numerous illnesses, including the common cold (echinacea), benign prostatic hypertrophy (saw palmetto), and depression (Saint Johnswort). Among patients with cancer, the use of unconventional medicines, including herbal therapies, has been reported to be as low as 5 percent and as high as 60 percent. PC-SPES is an herbal combination used by patients with prostate cancer that consists of eight herbs: chrysanthemum, isatis, licorice, Ganoderma lucidum, Panax pseudo-ginseng, Rabdosia rubescens, saw palmetto, and scutellaria (skullcap).Herbal therapies can have important biologic activities. For example, saw palmetto inhibits 5(alpha)-reductase, an enzyme involved in testosterone metabolism, and Saint Johnswort, like pharmacologic antidepressants, blocks monoamine oxidase activity. Although PC-SPES is promoted as a nonestrogenic food supplement, some of its constituents have estrogenic activity. Licorice competes with estradiol in an estrogen-receptor-binding assay,and ginseng induces estrogen-regulated expression of pS2, a small protein found in breast cancer, in cultured MCF-7 breast-cancer cells.The clinical implications of such activities are unknown.
We recently observed that PC-SPES had clinical activity in a man with prostate cancer that had recurred after radical prostatectomy. His prostate-specific antigen concentration was 34 ng per milliliter when he started taking PC-SPES, without concurrent therapies. After one month, he reported breast tenderness and loss of libido, and his prostate-specific antigen had decreased to 0.4 ng per milliliter. These findings prompted a study to determine the mechanism of these effects. Our results indicate that PC-SPES has estrogenic activity, reduces concentrations of serum testosterone, exerts activity against prostate cancer, and causes untoward side effects. Herbal mixtures are popular alternatives to demonstrated therapies. PC-SPES, a commercially available combination of eight herbs, is used as a nonestrogenic treatment for cancer of the prostate. Since other herbal medicines have estrogenic effects in vitro, we tested the estrogenic activity of PC-SPES in yeast and mice and in men with prostate cancer.
Methods. We measured the estrogenic activity of PC-SPES with transcriptional-activation assays in yeast and a biologic assay in mice. We assessed the clinical activity of PC-SPES in eight patients with hormone-sensitive prostate cancer by measuring serum prostate-specific antigen and testosterone concentrations during and after treatment.
Results. In complementary yeast assays, a 1:200 dilution of an ethanol extract of PC-SPES had estrogenic activity similar to that of 1 nM estradiol, and in ovariectomized CD-1 mice, the herbal mixture increased uterine weights substantially. In six of six men with prostate cancer, PC-SPES decreased serum testosterone concentrations (P<0.05), and in eight of eight patients it decreased serum concentrations of prostate-specific antigen. All eight patients had breast tenderness and loss of libido, and one had venous thrombosis. High-performance liquid chromatography, gas chromatography, and mass spectrometry showed that PC-SPES contains estrogenic organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol.
Conclusions. PC-SPES has potent estrogenic activity. The use of this unregulated mixture of herbs may confound the results of standard or experimental therapies and may produce clinically significant adverse effects. (N Engl J Med 1998;339:785-91.)