Testosterone: The Forgotten Hormone: Its Significance and Controversy, by James Orozco

Homeostasis is a finely-tuned regulatory system greatly influenced by chemicals called hormones.  When the body senses internal “red flags”, hormones are secreted into the blood directly or through ducts to offset the change within its system.  These chemicals can have a drastic effect on the body such as melatonin which regulates the circadian rhythm, vasopressin which constricts blood vessels to control blood pressure and oxytocin which promotes uterine contractions to name a few.   Testosterone, a sex hormone, is not limited to simply the development of sexual organs or sexual characteristics but affects mood, energy levels, fertility and libido¹.  More importantly is the profound effect upon overall health and mortality.

            First discovered in 1935, testosterone is only now receiving acknowledgement from the medical field as a crucial variable linked to obesity, depression, high-blood pressure, heart disease, Alzheimer’s disease and increased risk of mortality².  Nine years after the discovery of the hormone, the first study on testosterone was published in the Journal of the American Medical Association.  The research was conducted to examine any relation between health problems and a low testosterone level within the blood.  Researchers performed blood samples on sixty-three men, ages ranging from twenty-two to ninety-eight.  Of the sixty-three participants, twenty-five reported normal sexual function and no health complaints.  Within this group of healthy individuals it was discovered all were within normal testosterone levels.  The remaining thirty-eight individuals complained of health problems such as nervousness, irritability, insomnia, depression, antisocial tendencies, difficulty concentrating, headaches, increased pulse rates, hot flashes, fatigue, muscle pain, urinary problems, decreased erections and decreased libido.  Interestingly, twenty-three of the thirty-eight tested low in testosterone.  Subsequent research has confirmed the same effect low testosterone levels have on individuals³. Unfortunately, many doctors have not raised their brow to low testosterone levels when patients come into their offices complaining of the aforementioned symptoms.

            Hypogonadism is the medical term used to define a low testosterone level within the blood.  While mostly concerning men, it can also be diagnosed in women.  However, all women will undergo a drastic change within the body because of a phase of hormonal changes called menopause.  During this stage of a woman’s life, the estrogen and progesterone hormones plummet rapidly causing apparent signs and symptoms associated with hormonal deficiencies.  Symptoms include heart palpitations, hot flashes, joint aches and pains, night sweats, skin flushing, insomnia, decreased libido, forgetfulness and mood swings such as irritability and depression.  Aside from symptoms pertaining to the female anatomy such as vaginal dryness and irregular menstrual cycles, note the symptoms mimic those associated with hypogonadism. 

            The similarity between hypogonadism and menopause has lead to the term “Andropause,” basically, “Menopause for men.”  It is not medically recognized as a condition because of the controversy surrounding andropause.  Unlike menopause, which is sudden and abrupt, andropause is a slow, continuous decline in testosterone starting in the mid-thirties.  As a result of this steady decline, symptoms aren’t apparent and often deemed by the medical community as part of the aging process rather than a condition that warrants medical intervention.  In part, because a certain percentage of men, despite declining testosterone levels, are asymptomatic meaning they experience no symptoms.  The medical field has opted for the term, “Symptomatic Late-Onset Hypogonadism” (SLOH) as a more fitting name for a condition that justifies treatment.  Still controversy ensues because professionals argue symptoms are so gradual that many attribute them to stress, increase in workload or age causing inconclusive research.

            Despite the controversy concerning the appropriate name, andropause or SLOH is nonetheless a hormonal deficiency and if Testosterone Replacement Therapy (TRT) can reverse many of the symptoms associated with hypogonadism, treatment should ensue.  There are many other endocrine disorders such as hypothyroidism, Addison’s disease and Polycystic Ovary Syndrome all of which are supplemented with hormones to counter the hormone deficiency.  Patients suffering from hypothyroidism are given synthetic versions of the natural thyroid hormone called levothyroxine (T4).  Those afflicted with Addison’s disease, which is the body’s inability to produce cortisol and aldosterone, are given a corticosteroid named hydrocortisone which is similar to the natural cortisol hormone.  When viewed as an endocrine disorder such as these, hypogonadism warrants medical treatment. 

            Aging males who are asymptomatic can also benefit from (TRT).  It is concurred amongst medical doctors that TRT should only be used to treat symptomatic individuals.  However, recent research indicates a link between low testosterone and other health conditions such as diabetes⁴, obesity⁵, high-blood pressure⁶, heart disease⁷, increased risk of mortality⁸, and even Alzheimer’s disease⁹.  Should TRT be used as a preventative measure to reduce the risk of these conditions?   Also, should TRT be combined with current treatment options to treat these diseases?

            In 2009, the Department of Endocrinology and Medicine from the Melbourne University in Melbourne, Australia studied the correlation between testosterone and type II diabetes.   In a cross-sectional study of four hundred sixty-four men with type II diabetes, one hundred ninety-nine had low testosterone levels.  As more research is conducted, the relation between testosterone and diabetes is being increasingly recognized.  The Department of Clinical Physiopathology at the University of Florence in Italy, recognizing this relationship conducted a study to view the effects of TRT on patients with type II diabetes.  It was found that TRT reduced fat mass, reduced total cholesterol, reduced triglyceride levels and improved insulin sensitivity thereby reducing fasting blood glucose (FBG), postprandial blood glucose (PBG) and glycosilated haemoglobulin (HbA1c) levels and concluded, “Evidence suggests a positive effect on glycometabolic control.”  Another added benefit of TRT was improvement of erectile dysfunction⁴ which is a common complaint from those suffering from diabetes.

            Just as recent as of January 2010, obesity is quickly becoming the leading cause of preventable death in America according to the American Journal of Preventative Medicine surpassing smoking.  Obesity causes complications resulting in hypertension, high cholesterol, heart disease, heart attacks and strokes and can be effectively treated by increasing physical activity and eating healthy, low-fat meals.  While physical inactivity and poor food choices contribute to the rise of obesity in America, other factors can play a role in fat accumulation.  Hypothyroidism, Cushing’s syndrome, lack of sleep, depression and pregnancy are all conditions that can lead to overweight individuals.  The question is:  Does testosterone play a role as well? 

            According to the Massachusetts Study by New England Research Institute, as BMI levels, waist-to-hip ratios, and waist circumferences increased, their total testosterone, and free testosterone circulating within the blood decreased.  “These findings confirm previous reports of inverse associations between obesity and both TT and FT,” one sentence read.  Another stated, “Administration of testosterone has been shown to cause a reduction in central adiposity.”  It is unclear whether low testosterone causes weight gain or if weight gain causes a dip in testosterone levels as lower levels of testosterone causes more sugar and proteins to convert to fat instead of muscles.  Although, having a significant accumulation of fat causes an increase in aromatase which is an enzyme that converts testosterone into estrogen. 

            One of the most fascinating areas of interest regarding this special hormone is its effects on the heart.  The heart is the hardest working muscle within our bodies pumping roughly 2000 gallons of blood per day¹⁰.  The heart contains the most receptors for receiving testosterone than anywhere else in the human body being that testosterone, which is essentially a muscle-building hormone, is needed to ensure the heart is functioning efficiently.  As stated before, low testosterone is shown to increase cholesterol, increase triglycerides, raise blood pressure, and increase fat accumulation (especially central abdominal fat), all important factors in determining a person’s risk of developing heart disease.  Another risk of having low testosterone is an increase in fibrinogen and lipoprotein A.  Fibrinogen is a protein mixed in the blood to produce blood clotting.  While in essence, fibrinogen can be a useful deterrent from death by excessive blood loss when sustaining a large cut, too much of this protein can lead to strokes or heart attacks as blood becomes thicker and more sticky.  Lipoprotein A is a structure nearly identical to low-density lipoprotein more widely known as LDL.  A cholesterol count is a measure of two lipoproteins, high-density and low-density lipoprotein, (HDL and LDL respectively). The lipoprotein LDL is considered the “bad” cholesterol and increases the risks of heart disease as well as lipoprotein A because these lipoproteins tend to cling to the inner walls of your arteries obstructing blood flow to the heart. 

            A study by K. Channer was published in the European Heart Journal which stated: “Men with coronary artery disease have significantly lower levels of androgens than men with normal androgen levels, challenging the preconception that physiologically high levels of androgens in men account for their increased relative risk for coronary artery disease.”  A separate study by the Department of Physiology from the University of Hong Kong was performed following this conclusion to determine the effect of testosterone on the heart.  A group of lab rats were given large amounts of noradrenaline which increased the sympathetic nervous system which overworked the heart in an attempt to establish a myocardial infarction, more widely known as a heart attack.   The rats that were given a synthetic form of testosterone had a lesser risk of having a myocardial infarction thereby protecting the rats’ hearts.  This “cardio-protective effect” shows how testosterone may be useful in treating ischemic heart disease.  The article’s conclusion states:

“The present study has provided the first evidence that testosterone upregulated the expression of α-andrenoceptors and enhanced the cardiac responses to their stimulation, thus reducing cardiac injury.  Testosterone also improved contractile recovery and reduced arrhythmia upon ischaemia and reperfusion.”

As the evidence stacks up, it is apparent the profound effect testosterone has on the heart yet it is often overlooked within the medical community.  “The neglect is utterly puzzling, considering the depth of the research supporting its significance,” writes Eugene Shippen, M.D.

            New research is now indicating low testosterone levels and its relationship with a greater mortality risk.  A study of forty-four men in a geriatrics rehabilitation unit was conducted to evaluate whether low levels of testosterone equates to poorer function.  Of the forty-four men, twenty-nine tested positive for low testosterone levels.  Among this group, the length of rehabilitation increased and readmittances to hospitals increased. The research suggests those with low testosterone levels had higher mortality rates and chances of mortality within six months increased but was not statistically significant compared to the control group.  Can TRT add years to your life?  That’s what Malcolm Carruthers, M.D., an Andrologist argues.  In his book, The Testosterone Revolution, he mentions Greece as one country with the highest life expectancy.  There are many variables when determining causes for shorter or longer life expectancies, as many attribute their Mediterranean diet as a significant factor, but Carruthers refers to a study of Greek men with an interesting finding.  “A recent study of Greek men showed levels of testosterone at the upper limit of normal and very high rates of sexual activity,” Carruthers declares.  The author goes on to say that the testosterone hormone is the secret to vitality.  With unarguable evidence demonstrated by the above study, it’s not so much a secret anymore.

            Research is now indicating those with low blood levels of testosterone had an increased risk of developing Alzheimer’s.  The study comprised of five hundred seventy-four men, who were not diagnosed with Alzheimer’s, were followed for nineteen years on average.  The researchers concluded that for every 10 unit increase in testosterone their risk of developing Alzheimer’s decreased 26% even when considering age, education and smoking!  Another exciting find is TRT’s effectiveness in treating Alzheimer’s disease¹¹.  In 2005, neuroscientists at the UCLA Alzheimer’s Disease Research Center studied the effects of testosterone on Alzheimer’s patients.  Their research showed a significant improvement in memory, physical health, energy, interpersonal relationships and overall well-being compared to those who received a placebo.  “The results suggest testosterone replacement therapy holds potential for improving quality of life of Alzheimer patients and merits further testing,” states Dr. Po Lu, assistant clinical professor of neurology at UCLA.  Again, the recognition testosterone receives is “utterly puzzling.”

            By now, you may be asking yourself, “What can I do to determine whether or not my testosterone levels are within range?”  Evaluating levels of testosterone is inexpensive and as simple as a routine blood test.  By analyzing certain lab values such as the follicle-stimulating hormone (FSH), luteinizing hormone (LH), Free Testosterone and Total Testosterone, your primary physician can diagnose hypogonadism pending the results of the test.  Total testosterone is the amount of testosterone used by other proteins in the blood while free testosterone is the amount that is unbound and available for use.  There are two types of hypogonadism; primary and secondary and the FSH and LH values assists the physician in determining between primary and secondary in conjunction with low levels of testosterone.   Abnormally high levels of either FSH or LH indicate testicular dysfunction suggesting primary hypogonadism.  Conversely, abnormally low levels indicate dysfunction in the pituitary gland suggesting secondary hypogonadism. 

            A simple blood test evaluating these values can raise awareness in a treatable condition that, according to M. Carruthers, “can provide short and long-term improvement in the quality of life, and be of benefit in many serious and debilitating conditions, when carefully targeted it could be considered a strong candidate for providing cost-effective preventive medical care.”  Why has the medical community not given testosterone the recognition it merits?  Unfortunately, testosterone usually carries a negative connotation in part, because of a skewed public perception that testosterone results in aggression and hyper-sexuality.  Men also see it as a threat to their image as the “alpha male” concerning low testosterone and the bad publicity it receives, regarding anabolic steroids, doesn’t help either. 

Among doctors, it receives another skewed perception.  Early in the preliminary stages of evaluating effective treatment options for hypogonadism, a study found a correlation between testosterone supplementation and prostate cancer.  Subsequent research confirms that administering testosterone can speed up cancer in the prostate and currently, TRT is not recommended for this reason but the medical community interpreted causality and embedded fear in the minds of physicians however; there is no significant research that suggests TRT causes prostate cancer. A. Morgentaler, an urologist, regarding TRT and prostate cancer stated, “Any such link is declared to be a modern myth.  There is not now – nor has there ever been – a scientific basis for the belief that testosterone causes pCA to grow.”  However, a world-wide study evaluated the attitude of doctors concerning TRT and found that 60% are unwilling to prescribe testosterone therapy for “fear of inducing prostate cancer.”¹² The same study found that many physicians down-played testosterone’s role in serious medical conditions and found that they lacked training in safe and effective treatment options.

The U.S. health-care system emphasizes preventive care yet we are still not connecting the dots in regards to the effects and significance of testosterone.  Low testosterone levels have been linked to health conditions such as depression, obesity, heart disease, diabetes, hypertension and Alzheimer’s disease.  A study published in the International Journal of Clinical Practice states that hypogonadism was prevalent in 39% of primary care throughout the USA¹³.  Can we make good on that notion of “preventive care” by educating and training those that we turn to when we are sick?  Not only is TRT helpful in preventing these conditions, it is helpful in treating them as well.  It took decades before we realized the relationship between excessive smoking and lung cancer.  Within the past two decades we even realized that second-hand smoking can cause the same outcome which lead to legislation banning cigarette smoking in restaurants and bars to protect the employees subjected to the large amounts of toxic chemicals.  For years we used lead-based paint for our homes which resulted in mental retardation in kids who consumed the bits broken apart from repeated heat-cycles of summer-winter seasons.  For years we unknowingly subjected employees to remove and install building materials embedded with asbestos which we now know causes mesothelioma and malignant lung cancer.  When will we recognize the potential of TRT, the links associated with low testosterone levels and its impact on the health-care system?  Professor Lothar Heinemann from the Center for Men’s Health in London, UK states, “It could be said that the time has come regarding the need to diagnose and treat testosterone deficiency and should move from debate to action.” 

¹ Shippen, E., & Fryer W. (2001). The testosterone syndrome: The critical factor for energy,           health, and sexuality – Reversing the male menopause.  New York: Cambridge Press   

² Qaadri, S. (2004). The testosterone factor: The practical guide to improving vitality and virility.  New York: Oxford University Press

³Agledahl, I., Hansen, J., & Svartberg, J. (2008). Impact of testosterone treatment on postprandial triglyceride metabolism in elderly men with subnormal testosterone levels.  [Electronic Version]. Journal of clinical & Laboratory Investigation, Vol. 68. No.7, 641-648

⁴ Grossmann, M., et al. (2009). Low testosterone and anaemia in men with type 2 diabetes [Electronic Version]. Journal of Clinical Endocrinolgy, 70, 547-553

⁵ Isidori, A., et al. (2005).  Effects of testosterone on body composition, bone metabolism and lipid profile in middle-aged men: a meta-analysis [Electronic Version]. Journal of Clinical Endocrinology, 63, 280-293

⁶ El Hafidi, M., et al. (2006). Effect of sex hormones on non-esterified fatty acides, intra-abdominal fat accumulation and hypertension induced by sucrose diet in male subjects [Electronic Version]. Journal of Clinical & Expirimental Hypertension, Vol. 28, Issue 8, 669-681

⁷ English, K.M., et al. (2000). Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms [Electronic Version]. European Heart Journal 21, 890-894

⁸ Shores, M., et al. (2004). Low testosterone is associated with decreased function and increased mortality risk: A preliminary study of men in a geriatric rehabilitation unit [Electronic Version] JAGS 52, 2077-2081

⁹ Men’s testosterone levels tied to Alzheimer’s risk. (2004) Retrieved from http://www.medletters.com/

¹⁰ Bianco, C., (2010, Dec 1). How your heart works.  Retrieved December 1, 2010, from               http://health.howstuffworks.com/human-body/systems/circulatory/heart4.htm

¹¹ Baines, E., (2005). Testosterone helps in mild Alzheimer’s [Electronic Version] GP: General Practioner, 4-5

¹² Carruthers, M., (2009). Tune for international action on treating testosterone deficiency syndrome [Electronic Version] The Aging Male, 12, 21-28

¹³ Schneider, H., et al. (2009). Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study [Electronic Version] Journal of Clinical Endocrinology 70, 446-454

¹⁴ Tang, S., & Wong, T., (2008). Testosterone protects rat hearts against ischaemic insults by enhancing the effects of α₁- adrenoceptor stimulation [Electronic Version] British Journal of Pharmacology 153, 693-709

¹⁵ Corona, G., Mannucci, E., & Maggi, M., (2009).  Following the common association between testosterone deficiency and diabetes mellitus, can testosterone be regarded as a new therapy for diabetes? [Electronic Version] International Journal of Andrology 32, 431-441