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Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial


In a randomly allocated, double-blind, placebo-controlled, crossover design, 50 patients with mild to moderate erectile dysfunction (ED) were treated for 1 month with placebo or a combination of L-arginine aspartate and Pycnogenol (Prelox). Patients reported sexual function from diaries. Testosterone levels and endothelial NO synthase (e-NOS) were monitored along with routine clinical chemistry. Intake of Pycnogenol for 1 month restored erectile function to normal. Intercourse frequency doubled. e-NOS in spermatozoa and testosterone levels in blood increased significantly. Cholesterol levels and blood pressure were lowered. No unwanted effects were reported. Prelox is a promising alternative to treat mild to moderate ED.

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  1. Simonsen U, García Sacristán A, Prieto D . Penile arteries and erection. J Vasc Res 2002; 39: 283–303.

    Article  CAS  Google Scholar 

  2. Chen J, Wollman Y, Chermichovsky T, Iaina A, Sofer M, Matzkin H . Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU Int 1999; 83: 269–273.

    Article  CAS  Google Scholar 

  3. Klotz T, Mathers MJ, Braun M, Bloch W, Engelmann U . Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int 1999; 63: 220–223.

    Article  CAS  Google Scholar 

  4. Lebret T, Herve JM, Gorny P, Worcel M, Botto H . Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur Urol 2002; 41: 608–613.

    Article  CAS  Google Scholar 

  5. Fitzpatrick DF, Bing B, Rohdewald P . Endothelium-dependent vascular effects of Pycnogenol. Cardiovasc Pharmacol 1998; 32: 509–515.

    Article  CAS  Google Scholar 

  6. Durackova Z, Trebaticky B, Novotny V, Zitnanova A, Breza J . Lipid metabolism and erectile function improvement by Pycnogenol®, extract from the bark of Pinus pinaster in patients suffering from erectile dysfunction—apilot study. J Nutr Res 2003; 23: 1189–1198.

    Article  CAS  Google Scholar 

  7. Rohdewald P . Pycnogenol, French maritime pine bark extract. In: Encyclopedia of Dietary Supplements. Marcel Dekker: New York, 2005, pp 545–553.

    Google Scholar 

  8. USP monograph: maritime pine bark extract. The United States Pharmacopoeia, United States Pharmacopoeial Convention, US Pharmacopoeia 28, 2024–2025.

  9. Stanislavov R, Nikolova V . Treatment of erectile dysfunction with Pycnogenol® and L-arginine. J Sex Marital Ther 2003; 29: 207–213.

    Article  CAS  Google Scholar 

  10. Lamm S, Schönlau F, Rohdewald P . Prelox for improvement of erectile function: a review. Eur Bull Drug Res 2003; 11: 29–37.

    Google Scholar 

  11. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A . The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822–830.

    Article  CAS  Google Scholar 

  12. Stanislavov R, Nikolova V . Prelox® plus testosterone for achieve fertilization in previously infertile men. Eur Bull Drug Res 2005; 13: 7–13.

    Google Scholar 

  13. Raijfer J, Aronson W, Bush P, Dorey F, Ignarro L . Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to noradrenergic noncholinergic neurotransmission. N Engl J Med 1992; 326: 90–94.

    Article  Google Scholar 

  14. Cappelleri JC, Rosen RC, Smith MD, Mishra A, Osterloh IH . Diagnostic evaluation of the erectile function domain of the international index of erectile function. Urology 1999; 54: 346–351.

    Article  CAS  Google Scholar 

  15. Garban H, Vernet D, Freedman A, Raijfer J, Conzales-Cadavid N . Effect of aging on nitric oxide-mediated penile erection in rats. Am J Physiol 1995; 268: H467–H475.

    CAS  PubMed  Google Scholar 

  16. Carrier S, Nagaraju P, Morgan DM, Baba K, Nunes L, Lue TF . Age decreases nitric oxide synthase-containig nerve fibers in the rat penis. J Urol 1997; 157: 1088–1092.

    Article  CAS  Google Scholar 

  17. Smith AR, Visioli F, Frei B, Hagen TM . Age-related changes in endothelial nitric oxide synthase phosphorylation and nitric oxide dependent vasodilation: evidence for a novel mechanism involving sphingomyelinase and ceramide-activated phosphatase 2A. Aging Cell 2006; 5: 391–400.

    Article  CAS  Google Scholar 

  18. Wei ZH, Peng QL, Lau BHS . Pycnogenol® enhances endothelial cell antioxidant defenses. Redox Rep 1997; 3: 219–224.

    Article  CAS  Google Scholar 

  19. Zini A, O'Bryan MK, Magid MS, Schlegel PN . Immunohistochemical localization of endothelial nitric oxide synthase in human testis, epididymis, and vas deferens suggests a possible role for nitric oxide in spermatogenesis, Sperm maturation, and programmed cell death. Biol Reprod 1996; 55: 935–941.

    Article  CAS  Google Scholar 

  20. Soléru SG, Ennaji A, Cournot A, Spira A . LH pulsatile secretion and testosterone blood levels are influenced by sexual arousal in human males. Psychoneuroendocrinology 1993; 280: 205–218.

    Article  Google Scholar 

  21. Soléru S, Gregoire MC, Gerard D, Decety J, Lafarge E, Cinotti L et al. Neuroanatomical correlates of visually evoked sexual arousal in human males. Arch Sex Behav 1999; 28: 1–21.

    Article  Google Scholar 

  22. Heilhammer DH, Hubert W, Schürmeyer T . Changes in saliva testosterone after psychological stimulation in men. Psychoneuroendocrinology 1985; 10: 77–81.

    Article  Google Scholar 

  23. Schweiger U, Deuschle M, Weber B, Korner A, Lammer CH, Schmider J et al. Testosterone gonadotropin and cortisol secretion in male patients with major depression. Psychosomat Med 1999; 61: 292–296.

    Article  CAS  Google Scholar 

  24. Unden F, Ljunggren JG, Beck-Friis J, Kjellman BF, Wetterberg L . Hypothalamic-pituitary-gonadal axis in major depressive disorders. Acta Psychiatr Scand 1988; 78: 138–164.

    Article  CAS  Google Scholar 

  25. Hosseini S, Lee J, Sepulveda RT, Fagan T, Rohdewald P, Watson RR . A randomized, double blind, placebo controlled, prospective, 16 week crossover study to determine the role of Pycnogenol® in modifying blood pressure in mildly hypertensive patients. Nutr Res 2001; 21: 67–76.

    Article  Google Scholar 

  26. Liu X, Wei J, Tan F, Zhou S, Würthwein G, Rohdewald P . Pycnogenol®, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci 2004; 74: 855–862.

    Article  CAS  Google Scholar 

  27. Devaraj S, Vega-López S, Kaul N, Schönlau F, Rohdewald P, Jialal I . Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids 2002; 37: 931–934.

    Article  CAS  Google Scholar 

  28. Koch R . Comparative study of Venostasin® and Pycnogenol® for treatment in chronic venous insufficiency. Phytother Res 2002; 16: 1–5.

    Article  Google Scholar 

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We thank Dr J Gerß from the Institute of Medical Informatics and Biomathematics of the University Clinics Münster, Germany, for statistical evaluation of data. This study was funded by Horphag Research Ltd, UK.

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Correspondence to P Rohdewald.

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Competing Interests

Dr Stanislavov received a grant from Horphag Research Ltd to perform this study. Dr Rohdewald is a consultant for Horphag Research Ltd and holds a patent for the method of increasing sexual wellness with a combination of proanthocyanidins and L-arginine.

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Stanislavov, R., Nikolova, V. & Rohdewald, P. Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial. Int J Impot Res 20, 173–180 (2008).

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  • erectile dysfunction
  • Prelox
  • L-arginine
  • Pycnogenol
  • endothelial nitric oxide synthase (e-NOS)

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