Ambulatory and office urology| Volume 71, ISSUE 2, P185-190, February 2008

Effects of One-Year Treatment with Isoflavone Extract from Red Clover on Prostate, Liver Function, Sexual Function, and Quality of Life in Men with Elevated PSA Levels and Negative Prostate Biopsy Findings


      To asses the effect of an isoflavonoid extract from red clover on the prostate, liver function, quality of life, and sexual function in men with an initial elevated prostate-specific antigen (PSA) level and negative prostate biopsy findings during a 1-year treatment period.


      A total of 20 men (mean age 65 years) were treated with a daily 60-mg dose of an isoflavone extract for 1 year. Liver function, sexual hormone levels (total testosterone, estrogen, luteotropic hormone, follicle-stimulating hormone, and dehydroepiandrosterone sulfate), transrectal ultrasonography volumetry of the prostate, PSA level, International Prostate Symptom Score, and International Index of Erectile Function score were recorded at the beginning of the study and every 3 months for 1 year.


      The average PSA level was 10.16 ng/mL at baseline versus 7.15 ng/mL after 12 months, for a statistically significant reduction of 33% (P <0.019). The mean prostate volume had decreased slightly from 49.3 cm3 to 44.3 cm3 after 12 months (P <0.097). The sexual hormone levels did not change throughout the study. We registered a significant increase in all three liver transaminases after 3 months (P <0.001). The International Prostate Symptom Score showed a mean value of 7.9 at baseline and 6.68 after 12 months (P <0.421). Sexual function was not influenced by the treatment.


      Daily oral administration of 60 mg of an isoflavone extract was well tolerated and caused no side effects. The significant increase in liver transaminases and the significant decrease in total PSA levels by >30% indicates that patients, general practitioners, and urologists should be informed about these potential effects of red clover extracts and possibly other phytoestrogens, on liver transaminases and elevated total PSA levels.
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        • Adlercreutz H.
        Phyto-oestrogens and cancer.
        Lancet Oncol. 2002; 3: 364-372
        • Setchell K.D.R.
        Soy isoflavones—benefits and risks from nature’s selective estrogen receptor modulators (SERMs).
        J Am Coll Nutr. 2001; 20: 354-362
        • Magee P.J.
        • Rowland I.R.
        Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer.
        Br J Nut. 2004; 91: 513-531
        • Jarred R.A.
        • Keikha M.
        • Dowling C.
        • et al.
        Induction of apoptosis in low to moderate-grade human prostate carcinoma by red clover-derived dietary isoflavones.
        Cancer Epidemiol Biomarkers Prev. 2002; 11: 1689-1696
        • Davis J.N.
        • Muqim N.
        • Bhuiyan M.
        • et al.
        Inhibition of prostate specific antigen expression by genistein in prostate cancer cells.
        Int J Oncol. 2000; 16: 1091-1097
        • Rosenberg Zand R.S.
        • Jenkins D.J.A.
        • Brown T.J.
        • et al.
        Flavonids can blocks PSA production by breast and prostate cancer cell lines.
        Clin Chim Acta. 2002; 317: 17-26
      1. Cockett ATK: The International Consultation on Benign Prostate Hyperplasia (BPH) Proceedings June 27–30, 1993, Paris.

        • Rosen R.C.
        • Riley A.
        • Wagner G.
        • et al.
        The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction.
        Urology. 1997; 49: 822-825
        • DeVere White R.W.
        • Hackman R.M.
        • Soares S.E.
        • et al.
        Effects of a genistein-rich extract on PSA levels in men with a history of prostate cancer.
        Urology. 2004; 63: 259-263
        • Hussain M.
        • Banerjee M.
        • Sarkar F.H.
        • et al.
        Soy isoflavone in the treatment of prostate cancer.
        Nutr Cancer. 2003; 47: 111-117
        • Sun X.
        • Plouzek C.
        • Henry J.
        • et al.
        Increased UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells.
        Cancer Res. 1998; 58: 2379-2384
        • Risbridger G.P.
        • Wang H.
        • Frydenberg M.
        • et al.
        The in vivo effect of red clover diet on ventral prostate growth in adult male mice.
        Reprod Fertil Dev. 2001; 13: 325-329
        • Jarred R.A.
        • McPherson St. J.
        • Jones M.E.
        • et al.
        Anti-androgenic action by red clover-derived dietary isoflavones reduces non-malignant prostate enlargement in aromatase knockout (ArKO) mice.
        Prostate. 2003; 56: 54-64
        • Mathews J.M.
        • Etheridge A.S.
        • Black S.R.
        Inhibition of human cytochrome P450 activities by kava extract and kavactones.
        Drug Metab Dispos. 2002; 30: 1153-1157
        • Galati G.
        • O’Brien J.
        Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties.
        Free Radic Biol Med. 2004; 37: 287-303
        • Griffiths K.
        • Davies P.
        • Eaton C.
        • et al.
        Endocrine factors in the initiation, diagnosis and treatment of prostatic cancer, in Endocrine Dependent Tumours.
        in: Raven Press, New York1991: 83-130
        • Cicero A.F.G.
        • Derosa G.
        • Arletti R.
        Effect of oral isoflavones on male rat sexual performances and sexual hormone plasma levels.
        Phytother Res. 2004; 18: 849-852
        • Habito R.
        • Montalto J.
        • Lesile E.
        • et al.
        Effects of replacing meat with soybean in the diet on the sex hormone concentrations in healthy adult male.
        Br J Nutr. 2000; 84: 557-563
        • Allen N.
        • Appleby P.
        • Davey G.
        • et al.
        Soy milk intake in relation to serum sex hormone levels in British men.
        Nutr Cancer. 2001; 41: 41-46
        • Mitchell J.
        • Cawood E.
        • Kinniburgh D.
        • et al.
        Effect of a phytoestrogen food supplement on reproductive health on normal males.
        Clin Sci. 2001; 100: 613-618
        • Nagata C.
        • Takatsuka N.
        • Shimizu H.
        • et al.
        Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men.
        Cancer Epidemiol Biomarkers Prev. 2001; 10: 179-184
        • Denmark-Wahnefried W.
        • Price D.
        • Polascik T.
        • et al.
        Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate specific antigen and histopathologic features.
        Urology. 2001; 58: 47-52
        • Evans B.
        • Griffiths K.
        • Morton M.
        Inhibition of 5α-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids.
        J Endocrinol. 1995; 147: 295-302
        • Fritz W.
        • Coward L.
        • Wang J.
        • et al.
        Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat.
        Carcinogenesis. 1998; 19: 2151-2158
        • Rouse J.
        Kava: a South Pacific herb for anxiety, tension and insomnia.
        Clin Nutr Insights. 1998; 96: 3900-3905
        • Hausen B.
        • Wollenweber E.
        • Senff H.
        • et al.
        Propolis allergy, origin, properties usage and literature review.
        Contact Dermatitis. 1987; 17: 163-170
        • Auger J.
        • Kunstmann J.M.
        • Czyglik F.
        • et al.
        Decline in semen quality among fertile men in Paris during the past 20 years.
        N Engl J Med. 1995; 332: 281-285
        • Hess R.A.
        • Bunick D.
        • Lee K.H.
        • et al.
        A role for oestrogens in the male reproductive system.
        Nature. 1997; 390: 509-512
        • You L.
        • Sar M.
        • Bartolucci E.J.
        • et al.
        Modulation of mammary gland development in prepubertal male rats exposed to genistein and methoxychlor.
        Toxicol Sci. 2002; 66: 216-225