Dynamic Chiropractic Canada – January 1, 2014, Vol. 07, Issue 01
Giving Testosterone Levels a Boost
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
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
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
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
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
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, 1993 graduate of Parker College of Chiropractic, is the director of education for Progressive Laboratories.