Sildenafil or Viagra® has been on the market for several years.  We know it is effective in about 70% of the treatment group.  We use oral testosterone in some cases of low endogenous testosterone, but it also has limited effectiveness and carries hepatotoxicity warnings.  Alprostadil (Caverject), phentolamine or papaverine injections are sometimes used.  Others have tried Yohimbine, but it is rife with complications from kidney and cardiac to mental.  (Intrapenile intra-urethral suppositories and penile prosthesis implantation therapies are used in some circumstances). The more commonly used agents are only intended to be temporary treatments for the condition.  Most men, however, use these therapies as a chronic solution rather than seek alternate methods to solve their erectile dysfunction or ED challenges.  We are familiar with the acute side effects of sildenafil therapy, specifically the caveats with coadministration of nitrates and nitrites (Krenzelok, 2000; Webb et al., 2000; Mitka, 2003).   Nitrates and nitrites are central to the very prescriptions we give to our patients with chronic illnesses that usually create ED: hypertension, diabetes, ischemic heart disease, and hyperlipidemia.  Additionally, we often do not consider the long-term side effects of sildenafil and agents, like vardenafil (Levitra®) and tadalafil (Cialis®), that use similar mechanisms of action. A 4-year, open-label, flexible-dose NIH-Pfizer study with n=1,545 suggested that headache, dyspepsia, rhinitis and flushing were the only complications directly associated with treatment, long-term (McMurray, et al., 2007). Given the lack of long-range planning for patients using this and similar prescribed “short-term” agents, it is prudent for us to consider the most likely long-term solution for Erectile Dysfunction patients: complementary medicine.

Sildenafil, itself, does not have a “natural” equivalent.  There are some pure compounds found in nature that duplicate many of the functions of Sildenafil.  These include Citrulline, berberine, forskolin, Yohimbine (derived from evergreen tree bark in Congo), and the pyr ano-isofavones.  Korean red ginseng, Panax ginseng, has exhibited the most promising results from the herbal therapeutics in complementary medicine. Unlike fresh ginseng, which is less than 4-years-old or white ginseng, which is between 4–to-6 years old, peeled and dried, Korean red ginseng is harvested when it is 6-years-old, then steamed (unskinned) and dried.  In one study using 900 mg. doses thrice daily 45 patients with ED entered a double-blind, placebo controlled study of 8 weeks followed by 8 week’s crossover after a 2 week washout period. 60% of the patients experienced a significant erection improvement, as measured on penile tip RigiScan and penile duplex ultrasonography with audiovisual sexual stimulation (p <0.01), when taking Korean red ginseng (Hong, Ji, Hong, Nam, & Ahn, 2002).  Another study using 1,000 mg. thrice daily with 192 men in a randomized, double-blinded, case-control study demonstrated similar findings (De Andrade, et al., 2007).  A meta-analysis of 28 randomized controlled trials using Panax ginseng demonstrated similar findings, including positive results with the more challenging psychogenic erectile dysfunction (Jang, Lee, Shin, Lee, & Ernst, 2008).  Korean red ginseng, Panax ginseng, is as effective as cGMP-specific phosphodiesterase type 5 enzyme (PDE5) inhibitors (like sildenafil) enhancing the relaxation of the penile corpus cavernosum and treating male erectile dysfunction. This substance, unlike sildenafil, is better tolerated long-term.  Panax ginseng uses a mechanism of action that works as an antioxidant, lowering oxidative stress created by chronic illnesses such as diabetes, by enhancing endothelial nitric oxide (NO) synthesis.  

Protodioscin is an herbal agent created from the plant, Tribulus terrestris L.  Curiously, to obtain the active ingredient, the plant must be grown only in certain soils of Bulgaria and China (Adimoelja & Adaikan, 1997).  Its mechanism of action is the conversion of protodioscine to DHEA (De-Hydro-Epi-Androsterone). As such, Protodioscin uses DHEA, one of the male hormones, to naturally enhance sexual desire and enhance erection without undue simulation that is known to Sildenafil-type agents.

The African culture is rich with herbs, roots, and bark that have therapeutic benefit for ED.  The most accepted remedy in a culture that cannot afford the likes of prescription therapy is Mulondo Wine, a drink created from the roots of Mondia whiteii  (Kamatenesi-Mugisha & Oryem-Origa, 2005).

Hypercholesterolemia is often a leading source of ED.  Chronic disease associated with elevated cholesterol levels are often linked to ED, including smoking and obesity.  Still, prescription agents to lower cholesterol are not always an option when the patient is the informed decider of their fate.  Consider Chinese herbal medicine mixture!  Bakircioglu, et al. (2000) studied 32 Sprague-Dawley rats that were forced to develop hypercholesterolemia followed by a two month regimen of Chinese herbal medicine mixture.  2 months later, erectile function was evaluated with cavernous nerve electrostimulation.  Under electron microscopy the penile tissue was evaluated for endothelial nitric oxide synthase, neuronal nitric oxide synthase, basic fibroblast growth factor (bFGF) and caveolin-1.  Caveolin-1 and bFGF protein expression were significantly higher demonstrating probable protection of the cavernous smooth muscle and endothelial cells from the harmful effect of high serum cholesterol.  This reveals another mechanism of action to ED therapy that is a more long-term approach, rather than directly stimulating short-term erection.

Traditional Chinese medicine or TCM includes acupuncture, moxibustion, and Qigong.  Since 1985, these NIH-sanctioned therapies have been certified within the USA for more than pain.  Using the concepts of equal, yet opposing forces of Yin and Yang, the body flow of Qi is realigned along its meridian lines to restore sexual function (Crimmel, Conner & Monga, 2001). Herbs are burned at the ends of acupuncture needles (moxibustion) to draw more Qi to that region.  Qi is likened to the body’s immune system with its various nexuses aligned to the meridian lines. 

The ED population ingests an inordinate amount of pharmacological agents or has vasoactive substances inserted intraurethrally or injected intrapenially to regain good erection. It is known that thiomethisosildenafil-adulterated herbal remedies are marketed specifically to ED clients with their own set of untoward side effects and trail of ill will.  Popular names in this category include: Stamina-Rx, Max Size, Herbal Viva, Start Up, and Vigueur-7 (Balayssac, et al., 2009).  Still, traditional herbs have clinically proven mechanisms of action that support long-term, chronic therapy for the ED patient.  Phytochemicals focus on the root cause to chronicity that created a lack of control to adequate systemic sexual function.  Holding a solitary view acutely addressing the mechanism of erection is a short-sighted management plan.  Now is the time we should expand our scope of therapeutic options to consider complementary medicine for long-term management.  

References:

Adimoelja, A. (2000). Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions. International journal of andrology, 23(S2), 82-84.

Adimoelja, A., & Adaikan, P. G. (1997). Protodioscin from herbal plant Tribulus terrestris L improves the male sexual functions, probably via DHEA. Int. J. Impotence Res, 9, 1-15.

Balayssac, S., et al. (2009). 2D and 3D DOSY< sup> 1</sup> H NMR, a useful tool for analysis of complex mixtures: Application to herbal drugs or dietary supplements for erectile dysfunction. Journal of pharmaceutical and biomedical analysis, 50(4), 602-612.

Bakircioglu, M. E., et al. (2000). Effect of a Chinese herbal medicine mixture on a rat model of hypercholesterolemic erectile dysfunction. The Journal of urology, 164(5), 1798-1801.

Crimmel, A. S., Conner, C. S., & Monga, M. (2001). Withered Yang: a review of traditional Chinese medical treatment of male infertility and erectile dysfunction. Journal of andrology, 22(2), 173-182.

De Andrade, E., et al. (2007). Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian journal of andrology, 9(2), 241-244.

DeBusk, R. F., et al. (2004). Efficacy and safety of< i> sildenafil citrate</i> in men with erectile dysfunction and stable coronary artery disease. The American journal of cardiology, 93(2), 147-153.

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Fleshner, N., Harvey, M., Adomat, H., Wood, C., Eberding, A., Hersey, K., & Guns, E. (2005). Evidence for contamination of herbal erectile dysfunction products with phosphodiesterase type 5 inhibitors. The Journal of urology, 174(2), 636-641.

Goldstein, I., Lue, T. F., Padma-Nathan, H., Rosen, R. C., Steers, W. D., & Wicker, P. A. (1998). Oral sildenafil in the treatment of erectile dysfunction. New England Journal of Medicine, 338(20), 1397-1404.

Guirguis, W. R. (1998). Oral treatment of erectile dysfunction: from herbal remedies to designer drugs. Journal of sex & marital therapy, 24(2), 69-73.

Hong, B., Ji, Y. H., Hong, J. H., Nam, K. Y., & Ahn, T. Y. (2002). A double-blind crossover study evaluating the efficacy of Korean red ginseng in patients with erectile dysfunction: a preliminary report. The Journal of urology, 168(5), 2070-2073.

Jang, D. J., Lee, M. S., Shin, B. C., Lee, Y. C., & Ernst, E. (2008). Red ginseng for treating erectile dysfunction: a systematic review. British journal of clinical pharmacology, 66(4), 444-450.

Kamatenesi-Mugisha, M., & Oryem-Origa, H. (2005). Traditional herbal remedies used in the management of sexual impotence and erectile dysfunction in western Uganda. African health sciences, 5(1), 40-49.

Krenzelok, E. P. (2000). Sildenafil: Clinical toxicology profile. J. Toxicol. Clin. Toxicol., 38, 645–651.

McMurray, J. G., Feldman, R. A., Auerbach, S. M., DeRiesthal, H., Wilson, N., & Multicenter Study Group. (2007). Long-term safety and effectiveness of sildenafil citrate in men with erectile dysfunction. Therapeutics and clinical risk management, 3(6), 975.

Mitka, M. (2003). FDA issues warning on “all-natural” herbal product found to contain Viagra. J. Am. Med. Assoc., 289, 2786.

Sze-Yin Oh, S., Zou, P., Low, M. Y., & Koh, H. L. (2006). Detection of sildenafil analogues in herbal products for erectile dysfunction. Journal of Toxicology and Environmental Health, Part A, 69(21), 1951-1958.

Webb, D. J., et al. (2000). Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina. J. Am. Coll. Cardiol., 36, 25–31.

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