Dynamic Chiropractic – January 1, 2014, Vol. 32, Issue 01
dynamicchiropractic.com >> Patient Education
Giving Testosterone Levels a Boost
Health impact of "low normal" T and how to help patients.
By Kyl Smith, DC
In an analysis of more than 7,000 blood tests, one source reported, "More than 80% of men tested had less than optimal testosterone blood levels."1 ABC News, quoting the Journal of Clinical Endocrinology & Metabolism, stated, "1 in 4 Men Over 30 Has Low testosterone."2-3 Conservatively, this translates to more than 16 million men suffering with less than optimal testosterone in the United States today.4
A man suffering with "low normal" testosterone typically experiences mild to moderate fatigue, lethargy, tiredness and/or sapped motivation that just won't go away. Men contribute largely to the success of the "energy drink market," as they continually seek some form of artificial energy boost like caffeine throughout the day to attempt to feel "normal." Other symptoms of low testosterone are weight gain – especially abdominal fat, sagging physical stamina, loss of muscle tone, mild depression or mood swings.
The good news is that naturally enhancing this core hormone quickly and positively revitalizes every aspect of what it is to be a man, benefiting protein synthesis, enhancing skeletal muscle mass and bone density, and revitalizing mood, motivation, physical stamina; as well as improving cognitive functions like memory, mental performance and speed of reaction. In more subjective terms – restoring testosterone makes a man feel like he did when he was younger, more energetic, and vibrant.
More Science-Based "Low Normal" Testosterone Facts
- "Low normal" total testosterone concentrations are associated with reductions in motivation, initiative, self-confidence, concentration and memory, sleep quality, muscle bulk and strength, diminished physical or work performance, feeling sad or blue, depressed mood, mild anemia, and increased body fat and body mass index.5-6
- Low normal serum testosterone concentrations are associated with reduced male sexual desire, function, performance and potency.5-20
- Low normal serum testosterone concentrations increase the risk for premature death from any cause.21-29
- Low normal serum testosterone concentrations increase the risk for death from cardiovascular disease,21,23,25,28-29 and increase the combined risk for suffering a first stroke or first transient ischemic attack.30
- Low normal serum testosterone concentrations increase the risk for both memory loss31 and developing clinical depression.32
- Low normal serum testosterone concentrations increase the risk of developing an increased level of systemic inflammation.33-37
Defining "Healthy" Testosterone
Multiple peer-reviewed papers state that "testosterone deficiencies" are more prevalent and "desirable testosterone" levels in men are actually much higher than what is currently being considered as "normal" in doctors' practices across the country. Case in point: A cross-sectional study of Swedish men ages 69 to 80 years showed the risk for premature death from any cause26 and the risk for suffering a major cardiovascular event27 were inversely correlated with the total serum testosterone concentration (i.e., the higher the testosterone levels, the lower the risk of death).
Specifically with regards to cardiovascular events, men in the highest quartile of testosterone (at or higher than 550 ng/dL) had a lower risk of cardiovascular events compared with men with lower testosterone.27
More importantly, details from this study show that it did not matter if a man's total testosterone was very low (below 340 ng/dL ) or moderately low (up to 549 ng/dL ) – all men with T levels below 549 ng/dL had a similar increased risk for suffering a cardiovascular event. Only when total testosterone exceeded 550 ng/dL did cardiovascular risk drop.
This is truly alarming, as cardiovascular disease is the No. 1 killer of men in the United States and even more – this study was published in the Journal of the American College of Cardiology. These researchers documented a 30 percentreduction in cardiovascular events as well as a decrease in cerebrovascular disease incidence. Men with the highest total testosterone had a 24 percent reduced risk of transient ischemic attack or full-blown stroke.27 Clearly, based on this study, the only target for "healthy testosterone" is to maintain total testosterone at or above 550 ng/dL.
As a health care practitioner, please note the following:
- According to LabCorp, the "healthy reference range" for total testosterone is 348–1,197 ng/dL. So, the lower part of this range completely ignores recent science that shows total testosterone levels need to be maintained above 550 ng/dL.
- Subjectively, this broad range is ridiculous. As any 45-year-old man who has suffered with low normal testosterone knows,there is a world of difference in how a man feels and performs (both mentally and physically) when testosterone is "low normal" versus higher up the healthy "normal" reference range.
Stress / Cortisol: The "Testosterone Switch"
Acting through the classic glucocorticoid receptor, cortisol directly inhibits testosterone production in testicles by Leydig cells.38-40 The cortisol-receptor complex suppresses testosterone synthesis via inhibition of the expression of the steroidogenic acute regulatory protein – the very first step in testosterone synthesis.41 Even worse, hypercortisolemia inhibits testosterone synthesis,38-44 reduces the total testosterone concentration38-44 and accelerates the apoptosis (cell death) of Leydig cells.44 This is alarming because it means:
- Cortisol stops testosterone synthesis dead in its tracks at the very start of testosterone synthesis.
- Even worse, cortisol kills the cells in the testicles responsible for making testosterone in the future.
So, controlling hypercortisolemia is the key to generating healthy testosterone now and protecting testicular Leydig cells so they can continue to do their job and make testosterone in the future.
Cortisol Stimulates the Activity of the Aromatase Complex
Even worse (if there can be such a thing), cortisol stimulates the activity of the aromatase complex in human male fibroblasts and adipocytes in fat deposits throughout the body.45-48 Through this separate mechanism (completely different from inhibition of testosterone synthesis and secretion via Leydig cells, as just described), hypercortisolemia increases the conversion of circulating testosterone into estradiol, increases the serum estradiol concentration, decreases the serum total testosterone concentration, and increases the ratio of the serum estradiol concentration to the serum total testosterone concentration in men.38-40,42,43,45-48
Acute Stress Increases Cortisol, Decreases Testosterone
Acute stress, whether psychological (mentally stressed at work, finances, home, family, etc.) or the result of a physical challenge (surgery, injury or intense exercise), induces a significant increase in cortisol secretion in healthy men.49-50 For example, healthy men participating in a simulated job interview followed by a mental arithmetic test (real-world experiences designed to generate acute psychological stress), experienced a rapid significant increase in serum cortisol concentrations.51
Stress-induced elevations in serum cortisol concentration are associated with rapid declines in testosterone production by Leydig cells in the testicles.40 When male members of the ground crew of military aircraft were passengers on an acrobatic flight, they experienced acute anxiety that was accompanied by increased serum cortisol concentrations and decreased serum total testosterone concentrations.52 Similarly, young men about to board an aircraft for their first skydiving attempt (a purely psychological stressor) experienced an acute increase in cortisol concentration and an acute decrease in total testosterone concentration.53
During exposure to spontaneously occurring workplace psychological stress, 51-year-old men exhibited significantly decreased serum total testosterone concentrations.54 Healthy men receiving painful electrical shocks also experienced an acute increase in cortisol concentration and an acute decrease in total testosterone concentration.55
Editor's note: Look for part 2 of this article, in which Dr. Smith discusses treatment strategies for combating low normal testosterone, in an upcoming issue of DC.
- Faloon W. "Startling Low Testosterone Blood Levels in Male Life Extension Members." Life Extension, June 2010.
- Vann M. "1 in 4 Men Over 30 Has Low Testosterone." ABC News, Sept. 13, 2007.
- Age distribution, United States. CensusScope: http://censusscope.org/us/chart_age.html.
- Araujo AB, Esche GR, Kupelian V, O'Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab, 2007 Nov;92(11):4241-7.
- Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2010;95:2536-2559.
- Yeap BB, Hyde Z, Norman PE, Chubb SA, Golledge J. Associations of total testosterone, sex hormone-binding globulin, calculated free testosterone, and luteinizing hormone with prevalence of abdominal aortic aneurysm in older men. J Clin Endocrinol Metab, 2010;95:1123-1130.
- Seftel AD, Mack RJ, Secrest AR, Smith TM. Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning. J Androl, 2004;25:963-972.
- Martinez-Jabaloyas JM, Queipo-Zaragoza A, Pastor-Hernandez F, Gil-Salom M, Chuan-Nuez P. Testosterone levels in men with erectile dysfunction. BJU Int, 2006;97:1278-1283.
- Gray PB, Singh AB, Woodhouse LJ, Storer TW, Casaburi R, Dzekov J, Dzekov C, Sinha-Hikim I, Bhasin S. Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. J Clin Endocrinol Metab, 2005;90:3838-3846.
- Greco EA, Spera G, Aversa A. Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences. Eur Urol, 2006;50:940-947.
- Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab, 2006 Nov;91(11):4335-43.
- Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag, 2009;5:427-448.
- Baba K, Yajima M, Carrier S, Morgan DM, Nunes L, Lue TF, Iwamoto T. Delayed testosterone replacement restores nitric oxide synthase-containing nerve fibres and the erectile response in rat penis. BJU Int, 2000;85:953-958.
- Marin R, Escrig A, Abreu P, Mas M. Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol Reprod, 1999;61:1012-1016.
- Mills TM, Lewis RW, Stopper VS. Androgenic maintenance of inflow and veno- occlusion during erection in the rat. Biol Reprod, 1998;59:1413-1418.
- Park KH, Kim SW, Kim KD, Paick JS. Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int, 1999;83:327-333.
- Goglia L, Tosi V, Sanchez AM, Flamini MI, Fu XD, Zullino S, Genazzani AR, Simoncini T. Endothelial regulation of eNOS, PAI-1 and t-PA by testosterone and dihydrotestosterone in vitro and in vivo. Mol Hum Reprod, 2010;16:761-769.
- Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am, 2005;32:379-395.
- Mills TM, Wiedmeier VT, Stopper VS. Androgen maintenance of erectile function in the rat penis. Biol Reprod, 1992;46:342-348.
- Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab, 2008;93:68-75.
- Lehtonen A, Huupponen R, Tuomilehto J, Lavonius S, Arve S, Isoaho H, Huhtaniemi I, Tilvis R. Serum testosterone but not leptin predicts mortality in elderly men. Age Ageing, 2008;37:461-464.
- Hyde Z, Norman PE, Flicker L, Hankey GJ, Almeida OP, McCaul KA, Chubb SA, Yeap BB. Low free testosterone predicts mortality from cardiovascular disease but not other causes: the Health in Men Study. J Clin Endocrinol Metab, 2012;97:179-189.
- Jankowska EA, Rozentryt P, Ponikowska B, Hartmann O, Kustrzycka-Kratochwil D, Reczuch K, Nowak J, Borodulin-Nadzieja L, Polonski L, Banasiak W, Poole-Wilson PA, Anker SD, Ponikowski P. Circulating estradiol and mortality in men with systolic chronic heart failure. JAMA, 2009;301:1892-1901.
- Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart, 2010;96:1821-1825.
- Tivesten A, Vandenput L, Labrie F, Karlsson MK, Ljunggren O, Mellström D, Ohlsson C. Low serum testosterone and estradiol predict mortality in elderly men. J Clin Endocrinol Metab, 2009;94:2482-2488.
- Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, Mellström D, Tivesten A. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) Study in Sweden. J Am Coll Cardiol, 2011;58:1674-1681.
- Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation, 2007;116:2694-2701.
- Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab, 2011;96:3007-3019.
- Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SA, Jamrozik K, Flicker L, Hankey GJ. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. J Clin Endocrinol Metab, 2009;94:2353-2359.
- Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab, 2002;87:5001-5007.
- Almeida OP, Yeap BB, Hankey GJ, Jamrozik K, Flicker L. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch Gen Psychiatry, 2008;65:283-289.
- Kupelian V, Chiu GR, Araujo AB, Williams RE, Clark RV, McKinlay JB. Association of sex hormones and C-reactive protein levels in men. Clin Endocrinol, 2010;72:527-533.
- Black S, Kushner I, Samols D. C-reactive protein. J Biol Chem, 2004;279:48487- 48490.
- Helaly MA, Daoud E, El-Mashad N. Does the serum testosterone level have a relation to coronary artery disease in elderly men? Curr Gerontol Geriatr Res, 2011;2011:791765.
- Bobjer J, Katrinaki M, Tsatsanis C, Lundberg Giwercman Y, Giwercman A. Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One, 2013;8:e61466.
- Kim S, Kwon H, Park JH, Cho B, Kim D, Oh SW, Lee CM, Choi HC. A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease. BMC Gastroenterol, 2012;12:69.
- Fenske M. Role of cortisol in the ACTH-induced suppression of testicular steroidogenesis in guinea pigs. J Endocrinol, 1997;154:407-414.
- Welsh TH Jr, Bambino TH, Hsueh AJ. Mechanism of glucocorticoid-induced suppression of testicular androgen biosynthesis in vitro. Biol Reprod, 1982;27:1138-1146.
- Hu GX, Lian QQ, Lin H, Latif SA, Morris DJ, Hardy MP, Ge RS. Rapid mechanisms of glucocorticoid signaling in the Leydig cell. Steroids, 2008;73:1018- 1024.
- Clark BJ, Wells J, King SR, Stocco DM. The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J Biol Chem, 1994;269:28314-28322.
- Martin LJ, Tremblay JJ. Glucocorticoids antagonize cAMP-induced Star transcription in Leydig cells through the orphan nuclear receptor NR4A1. J Mol Endocrinol, 2008;41:165-175.
- Wang X, Walsh LP, Reinhart AJ, Stocco DM. The role of arachidonic acid in steroidogenesis and steroidogenic acute regulatory (StAR) gene and protein expression. J Biol Chem, 2000;275:20204-20209.
- Gao HB, Tong MH, Hu YQ, Guo QS, Ge R, Hardy MP. Glucocorticoid induces apoptosis in rat Leydig cells. Endocrinology, 2002;143:130-138.
- McTernan PG, Anderson LA, Anwar AJ, Eggo MC, Crocker J, Barnett AH, Stewart PM, Kumar S. Glucocorticoid regulation of p450 aromatase activity in human adipose tissue: gender and site differences. J Clin Endocrinol Metab, 2002;87:1327-1336.
- Schmidt M, Renner C, Löffler G. Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts. J Endocrinol, 1998;158:401-407.
- Simpson ER, Ackerman GE, Smith ME, Mendelson CR. Estrogen formation in stromal cells of adipose tissue of women: induction by glucocorticosteroids. Proc Natl Acad Sci (USA), 1981;78:5690-5694.
- Wang W, Li J, Ge Y, Li W, Shu Q, Guan H, Yang K, Myatt L, Sun K. Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway. Endocrinology, 2012;153:2012-2022.
- Jezova D, Duncko R, Lassanova M, Kriska M, Moncek F. Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb761) in healthy volunteers. J Physiol Pharmacol, 2002;53:337-348.
- Harbuz MS, Lightman SL. Stress and the hypothalamo-pituitary-adrenal axis: acute, chronic and immunological activation. J Endocrinol, 1992;134:327-339.
- Lennartsson AK, Kushnir MM, Bergquist J, Billig H, Jonsdottir IH. Sex steroid levels temporarily increase in response to acute psychosocial stress in healthy men and women. Int J Psychophysiol, 2012;84:246-253.
- Leedy MG, Wilson MS. Testosterone and cortisol levels in crewmen of U.S. Air Force fighter and cargo planes. Psychosom Med, 1985;47:333-338.
- Chatterton RT Jr, Vogelsong KM, Lu YC, Hudgens GA. Hormonal responses to psychological stress in men preparing for skydiving. J Clin Endocrinol Metab, 1997;82:2503-2509.
- Rosmond R, Dallman MF, Björntorp P. Stress-related cortisol secretion in men: Relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab, 1998;83:1853-1859.
- Choi JC, Chung MI, Lee YD. Modulation of pain sensation by stress-related testosterone and cortisol. Anaesthesia, 2012;67:1146-1151.
Dr. Kyl Smith, a 1993 graduate of Parker College of Chiropractic, is the director of education for Progressive Laboratories and author of the book The Testosterone Switch, which includes hundreds of references for diet, exercise and nutritional supplements that increase testosterone levels in men.