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Life Extension Magazine

LE Magazine October 2005
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Integrative Management of Erectile Dysfunction

By Dr. Sergey A. Dzugan

Commentary

The age-related changes in men that occur after the age of 40 have generated worldwide interest in hormone supplementation. In cases of endocrine deficiencies, traditional endocrinology aims to replace the missing hormone or hormones. Interventions such as hormone replacement therapy may favorably influence some of the pathological conditions, such as erectile dysfunction, that occur in aging men. Aging is associated with diminished total and bioavailable testosterone concentrations, a lower ratio of testosterone to estradiol, and decreased levels of DHEA, DHEA-sulfate, thyroid hormones, growth hormone, and melatonin. Additionally, sex hormone binding globulin (SHBG) increases with age, resulting in a decreased concentration of free testosterone.7,19 Testosterone deficiency is likely to be a primary contributor to sexual dysfunction in many cases of erectile dysfunction.39

Upon interviewing this patient during his initial visit, we realized that conventional ED treatment had little chance of successfully resolving his condition. Because of the patient’s very high serum cholesterol level, we suspected that he might have several hormonal deficiencies. Conventional testosterone replacement therapy had stopped working for this patient several years ago, and his serum testosterone level was low, despite being treated with a larger dose of testosterone every year.

We therefore decided on a new strategy. First, we needed to restore youthful levels of all the steroid hormones, not just testosterone. Second, we needed to block enzymes (5-alpha reductase and aromatase) responsible for the “leakage,” or conversion, of testosterone to the less desirable hormones, dihydrotestosterone (DHT) and estradiol. Third, we needed to increase the level of free testosterone by preventing the binding of testosterone to sex hormone binding globulin (SHBG) through the use of supplements such as nettle root.

Our approach with this patient differed from standard management of erectile dysfunction. First, we tried to restore the normal feedback mechanism of the neuroendocrinological system, which is important for maintaining the homeostasis, or dynamic equilibrium, of steroid hormones. Furthermore, we wanted to restore youthful physiology by supporting the regulation of cholesterol metabolic pathways. Decreased DHEA and DHEA-sulfate production with age can contribute to diminished testosterone formation.40 We suggested a high dose of DHEA in this case to restore optimal levels of DHEA and DHEA-sulfate.

Additionally, we sought to encourage the conversion of DHEA to androstenedione, androstenediol, and testosterone. DHEA was a very important element of restoring the patient’s testosterone level, allowing us to use a smaller dose of testosterone than would have been required using testosterone replacement therapy alone.

In this case, blood testing was very helpful in detecting suboptimal levels of several hormones in addition to low testosterone.

Furthermore, we believe that cholesterol was a very important biomarker for baseline evaluation, as well as a means to monitor the treatment plan’s effectiveness.

Normally, testosterone can convert to dihydrotestosterone (DHT), androstanediol, and estradiol. With age, the conversion of testosterone to DHT and estradiol increases, as does the production of sex hormone binding globulin (SHBG). These factors contribute to a reduced amount of free testosterone in the body. To help restore youthful physiology, we aimed to prevent the conversion of testosterone to DHT by using supplements that block the 5-alpha reductase enzyme. Furthermore, we used the natural aromatase inhibitors progesterone and zinc to help prevent the conversion of testosterone to estradiol.41,42 Additionally, we used an herbal extract that inhibits the binding of testosterone to SHBG. Through these interventions, we sought to achieve a higher level of endogenous testosterone.

The following supplements have some potential use for testosterone metabolism:

  • saw palmetto: 5-alpha reductase inhibitor in the prostate gland43,44
  • nettle root: 5-alpha reductase inhibitor; inhibits the binding of testosterone and SHBG45-47
  • Pygeum africanum: has an inhibitory effect on prostate cell proliferation48,49
  • zinc: aromatase inhibitor41
  • progesterone: 5-alpha reductase inhibitor; aromatase inhibitor.42,50

As noted previously, stimulation of the parasympathetic nervous system can lead to a release of nitric oxide from the terminal end of axons, leading to vasodilation. That is why we recommended two agents that increase activity of the parasympathetic system: progesterone and MetaRest® (melatonin, kava root, and vitamin B6). In addition to parasympathetic stimulation, MetaRest® can help promote a vasodilating effect because of kava root’s effect of being a mild calcium channel blocker.51

In this patient, blood tests indicated a low-normal level of progesterone, but we opted to elevate that level to the high side of normal to support the parasympathetic system and further inhibit the aromatase enzyme. Progesterone is vital for good health, in men as well as in women. In men, progesterone is made by the adrenal glands and the testes. It is the precursor of the adrenal cortical hormones and androgens. All men over 40 should consider natural progesterone replacement therapy. Progesterone can be considered as a physiological suppressor of aromatase induction in adipose tissue.42 Also, progesterone can inhibit 5-alpha reductase’s conversion of testosterone to DHT.50 Through these effects, progesterone promotes higher levels of endogenous testosterone.

This case report stresses the importance of restoring youthful hormone levels and physiology in a man who suffered from erectile dysfunction. Restoration of all of the important steroid hormones—not just testosterone—helped to normalize this man’s high cholesterol level in addition to resolving his chronic erectile dysfunction.

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