Life Extension Magazine October 2005
Integrative Management of Erectile Dysfunction
By Dr. Sergey A. Dzugan
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:
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.
1. Aversa A, Fabbri A. New oral agents for erectile dysfunction: what is changing in our practice? Asian J Androl. 2001 Sep;3(3):175-9.
2. McKay D. Nutrients and botanicals for erectile dysfunction: examining the evidence. Altern Med Rev. 2004 Mar;9(1):4-16.
3. Fabbri A, Aversa A, Isidori A. Erectile dysfunction: an overview. Hum Reprod Update. 1997 Sep;3(5):455-66.
4. Rampin O. Neural control of erection. J Soc Biol. 2004;198(3):217-30.
5. Kloner RA, Mullin SH, Shook T, et al. Erectile dysfunction in the cardiac patient: how common and should we treat? J Urol. 2003 Aug;170(2 Pt 2):S46-S50.
6. Meuleman EJ. Prevalence of erectile dysfunction: need for treatment? Int J Impot Res. 2002 Feb;14 Suppl 1S22-8.
7. Lunenfeld B. Aging men—challenges ahead. Asian J Androl. 2001 Sep;3(3):161-8.
8. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994 Jan;151(1):54-61.
9. Mota M, Lichiardopol C, Mota E, Panus C, Panus A. Erectile dysfunction in diabetes mellitus. Rom J Intern Med. 2003;41(2):163-77.
10. Peate I. The effects of smoking on the reproductive health of men. Br J Nurs. 2005 Apr 14;14(7):362-6.
11. Gazzaruso C. Current opinions on the relationships between athero-thrombosis, type 2 diabetes mellitus and erectile dysfunction. Recenti Prog Med. 2005 Mar;96(3):155-8.
12. Fowler CJ, Miller JR, Sharief MK, et al. A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2005 May;76(5):700-5.
13. Magerkurth C, Schnitzer R, Braune S. Symptoms of autonomic failure in Parkinson’s disease: prevalence and impact on daily life. Clin Auton Res. 2005 Apr;15(2):76-82.
14. Ashraf VV, Taly AB, Nair KP, Rao S, Sridhar. Role of clinical neurophysiological tests in evaluation of erectile dysfunction in people with spinal cord disorders. Neurol India. 2005 Mar;53(1):32-5.
15. Virag R, Floresco J, Richard C. Impairment of shear-stress-mediated vasodilation of cavernous arteries in erectile dysfunction. Int J Impot Res. 2004 Feb;16(1):39-42.
16. Kim YC. Hormonal replacement therapy and aging: Asian practical recommendations on testosterone supplementation. Asian J Androl. 2003 Dec;5(4):339-44.
17. Prikhozhan VM, Kuroedova IA. Plasma testosterone levels of diabetic men. Probl Endokrinol (Mosk). 1975 Sep;21(5):18-23.
18. Alexopoulou O, Jamart J, Maiter D, et al. Erectile dysfunction and lower androgenicity in type 1 diabetic patients. Diabetes Metab. 2001 Jun;27(3):329-36.
19. Lunenfeld B. Androgen therapy in the aging male. World J Urol. 2003 Nov;21(5):292-305.
20. Reiter WJ, Pycha A, Schatzl G, et al. Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction. Urology. 2000 May;55(5):755-8.
21. Galbraith RA. Sexual side effects of drugs. Drug Ther (NY). 1991 Mar;21(3):38-40.
22. Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med. 1998 May 14;338(20):1397-404.
23. Chen J, Wollman Y, Chernichovsky T, et al. 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 Feb;83(3):269-73.
24. Hong B, Ji YH, Hong JH, Nam KY, Ahn TY. A double-blind crossover study evaluating the efficacy of korean red ginseng in patients with erectile dysfunction: a preliminary report. J Urol. 2002 Nov;168(5):2070-3.
25. Mahajan SK, Abbasi AA, Prasad AS, et al. Effect of oral zinc therapy on gonadal function in hemodialysis patients. A double-blind study. Ann Intern Med. 1982 Sep;97(3):357-61.
26. Reiter WJ, Pycha A, Schatzl G, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology. 1999 Mar;53(3):590-4.
27. Reiter WJ, Pycha A. Placebo-controlled dihydroepiandrosterone substitution in elderly men. Gynakol Geburtshilfliche Rundsch. 1999;39(4):208-9.
28. Reiter WJ, Schatzl G, Mark I, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction in patients with different organic etiologies. Urol Res. 2001 Aug;29(4):278-81.
29. Belaisch J. DHEA: desire and resistance. Gynecol Obstet Fertil. 2002 Dec;30(12):961-9.
30. Vakina TN, Shutov AM, Shalina SV, Zinov’eva EG, Kiselev IP. Dehydroepiandrosterone and sexual function in men with chronic prostatitis. Urologiia. 2003 Jan;(1):49-52.
31. Derouet H, Lehmann J, Stamm B, et al. Age dependent secretion of LH and ACTH in healthy men and patients with erectile dysfunction. Eur Urol. 2002 Feb;41(2):144-53.
32. Gonzales GF, Cordova A, Vega K, et al. Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Andrologia. 2002 Dec;34(6):367-72.
33. Adimoelja A. Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions. Int J Androl. 2000;23 Suppl 282-84.
34. Vogt HJ, Brandl P, Kockott G, et al. Double-blind, placebo-controlled safety and efficacy trial with yohimbine hydrochloride in the treatment of nonorganic erectile dysfunction. Int J Impot Res. 1997 Sep;9(3):155-61.
35. Ernst E, Pittler MH. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol. 1998 Feb;159(2):433-6.
36. Slob AK, Verhulst AC, Gijs L, Maksimovic PA, van der Werff ten Bosch JJ. Intracavernous injection during diagnostic screening for erectile dysfunction; five-year experience with over 600 patients. J Sex Marital Ther. 2002 Jan;28(1):61-70.
37. Dzugan SA, Arnold SR. Hypercholesterolemia treatment: a new hypothesis or just an accident? Med Hypotheses. 2002 Dec;59(6):751-6.
38. Dzugan, S.A., Smith, R.A., Kuznetsov A.S. A new statin free method of hypercholesterolemia. The Health of Donbass. 2004;4:19-25.
39. Kandeel FR, Koussa VK, Swerdloff RS. Male sexual function and its disorders: physiology, pathophysiology, clinical investigation, and treatment. Endocr Rev. 2001 Jun;22(3):342-88.
40. Morley JE, Kaiser F, Raum WJ, et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA. 1997 Jul 8;94(14):7537-42.
41. Om AS, Chung KW. Dietary zinc deficiency alters 5 alpha-reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver. J Nutr. 1996 Apr;126(4):842-8.
42. Schmidt M, Renner C, Loffler G. Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts. J Endocrinol. 1998 Sep;158(3):401-7.
43. Habib FK, Ross M, Ho CK, Lyons V, Chapman K. Serenoa repens (Permixon) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression. Int J Cancer. 2005 Mar 20;114(2):190-4.
44. Bayne CW, Donnelly F, Ross M, Habib FK. Serenoa repens (Permixon): a 5alpha-reductase types I and II inhibitor-new evidence in a coculture model of BPH. Prostate. 1999 Sep 1;40(4):232-41.
45. Sokeland J. Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome. BJU Int. 2000 Sep;86(4):439-42.
46. Hryb DJ, Khan MS, Romas NA, Rosner W. The effect of extracts of the roots of the stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic membranes. Planta Med. 1995 Feb;61(1):31-2.
47. Schottner M, Gansser D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG). Planta Med. 1997 Dec;63(6):529-32.
48. Anon. Pygeum africanum (Prunus africanus) (African plum tree). Monograph. Altern Med Rev. 2002 Feb;7(1):71-4.
49. Santa Maria MA, Paciucci BR, Reventos PJ, Morote RJ, Thomson Okatsu TM. Antimitogenic effect of Pygeum africanum extracts on human prostatic cancer cell lines and explants from benign prostatic hyperplasia. Arch Esp Urol. 2003 May;56(4):369-78.
50. Tilakaratne A, Soory M. Effects of the anti-androgen finasteride on 5 alpha-reduction of androgens in the presence of progesterone in human gingival fibroblasts: modulatory actions of the alkaline phosphatase inhibitor levamisole. J Periodontal Res. 2000 Aug;35(4):179-85.
51. Singh YN, Singh NN. Therapeutic potential of kava in the treatment of anxiety disorders. CNS Drugs. 2002;16(11):731-43.