Dietary Supplement Tied to Metastatic Prostate Cancer

By Crystal Phend
DALLAS, Jan. 15 -- When two patients developed unusually aggressive metastatic prostate cancer within months of starting the same muscle-building dietary supplement, researchers here started investigating. The supplement contained testosterone and estradiol but promoted cancer cell growth more potently than testosterone alone while hampering androgen blockade, found Shahrokh F. Shariat, M.D., of the University of Texas Southwestern Medical Center here, and colleagues, in the Jan. 15 issue of Clinical Cancer Research.
Although the product was taken off the market after they reported the two cases as adverse events to the FDA, the researchers said similar hormonal or dietary supplements still being sold might speed prostate cancer progression and impair treatment.
"Given that testosterone supplements are in high demand," they said, "there is significant concern that herbal/hormonal dietary supplements other than the one evaluated in the current study may pose an urgent human health risk."
Androgenic steroid product sales have been exponentially increasing, in part, because patients believe supplements to be safe and drug-free, Dr. Shariat and colleagues wrote.
Thus, physicians should routinely assess patients, particularly cancer patients, for use of supplements, explain the risks, and monitor for possible interactions and side effects, they added.
In both cases the researchers reported to the FDA, the patients purchased the product, via the Internet, for increased muscle mass or improved sexual performance, or both.
The labeled ingredients included 60 mg of a proprietary blend of six testosterone precursors (androstenediones and androstenediols), 100 mg of the aromatase inhibitor-like flavinoid chrysin, and 100 mg of elk velvet antler per serving.
After 10 to 11 months of use of the product, both patients developed prostate problems.
One, a 67-year-old white male, presented with a non-productive cough, frequent urination, and loss of appetite with involuntary weight loss of more than 40 pounds.
Despite two normal prostate cancer screenings over the prior two years, his total serum prostate-specific antigen (tPSA) level had jumped to 74 ng/mL. In addition to prostate cancer with a Gleason score of 6, he had developed metastatic disease in both lungs and the right rib cage, upper lumbar spine, right sacrum, and both pubic rami.
The other patient, a 51-year-old African-American male had a spike in tPSA (21.7 ng/mL) at his yearly prostate cancer screening after starting on the product despite normal screening results over the prior two years.
He had developed prostate cancer with a Gleason score of 7, with extracapsular extension, seminal vesicle involvement, pelvic lymph node enlargement, and multiple small metastases in both lungs and two vertebrae.
Both patients discontinued the supplement after diagnosis, but had widely metastatic disease at last follow-up despite androgen blockade therapy and palliative radiation therapy.
Neither patient had androgen receptor gene mutations that have been associated with aggressive disease, disease progression, and metastasis.
"A cancer that was most likely nonsignificant or would never have affected them in their lives became so aggressive that it basically led to the spread of the cancer," Dr. Shariat said. "This is an unheard of progression for prostate cancer."
When his group ran tests on the supplement product used by the men, they found it "listed ingredients that were not present, misrepresented the concentrations of the ingredients present, and failed to list all the steroids."
And, it contained at least one endocrinologically active component that promoted tumor growth independent of androgen receptor status.
Hormone-refractory and hormone-sensitive human prostate cancer cell lines grew more in the presence of the dietary supplement than with testosterone, and the cancer growth was dose-dependent.
The anti-androgen bicalutamide (Casodex) only transiently blocked cancer cell proliferation when the supplement used by the men was present.
"These findings suggest that the herbal/hormone dietary supplement product stimulates prostate cancer cell growth, effectively bypassing the androgen receptor pathway in prostate cancer cells, while also rendering the cancer cells resistant to standard anti-androgen therapy."
However, they cautioned that their results could not draw a causative link between the product and development and progression of prostate cancer.
Further research is needed to define the safety and efficacy of other common supplements, Dr. Shariat and colleagues concluded.
However, the Dietary Supplement Health and Education Act of 1994 gave manufacturers sole responsibility for ensuring efficacy and safety of their products with little oversight from the FDA.
"We do not know if there are other products out there with the same effect out there," Dr. Shariat said. "We will not know unless these products are screened and tested like normal drugs."
Dr. Shariat reported no conflicts of interest.
Primary source: Clinical Cancer ResearchSource reference:Shariat SF, et al "A herbal/hormonal dietary supplement: an association with prostate cancer progression?" Clin Cancer Res 2008; 14.