By Daniel Gwartney, MD
There is clear evidence that man is healthiest when his testosterone concentration is in the mid- to upper-limits of the physiologic range.
On a cloudy day, time moves less clearly than it does on a sunny day. Harken back to the summer days of youth, before the responsibilities of a job or family required one to pay attention to the passage of time. It wasn’t until the streetlights went on that one realized the sun had set and night had covered the neighborhood in a cloak of darkness. The activity on the streets settle as children are called in, even the dogs and squirrels sought shelter as they prepare for their nocturnal slumber.
A man’s physiology undergoes a similar change as time passes, though on a much grander scale. In decades, rather than hours, the “sunshine” of youthfulness passes gradually as the “darkness” of aging suppresses many activities in the body. Among the many documented changes that occur with aging is a clear decline in the concentration of testosterone. Testosterone is a naturally occurring hormone that is responsible, either directly or through one of its metabolites – dihydrotestosterone (DHT) and estradiol (E2) – for promoting anabolic processes in many tissues, as well as initiating and maintaining secondary sexual characteristics. Testosterone is often referred to as the male sex hormone, but it is shortsighted to pigeonhole testosterone to a single set of processes. Testosterone obviously promotes muscle mass and sexual/reproductive function, but it also affects bone density, red blood cell mass, hair growth patterns, organ function, fat cell metabolism, stem cell differentiation, etc.
The Fluctuating Hormone
Testosterone is not a static presence in the blood. Its “normal” concentration varies among age groups, races and individuals; even in the same person, it not only varies from season to season, but hour to hour. If a man’s serum (blood) testosterone concentration were plotted on a graph, it would have as many ups and downs as the stock market has shown over time. To complicate matters further, the effects of testosterone are not dependent solely upon the concentration of testosterone in the blood (serum), but also on androgen receptor density, structure, converting enzymes, co-factors (both activators and suppressors), genotype, nutritional status, non-genomic receptors, etc. Even when restricting the evaluation of a man’s androgen status to serum testosterone measures, there remain a number of variables, including: sex hormone-binding globulin (SHBG); albumin; total versus free versus bioavailable; E2; DHEA; etc.
To be fair, few people understand the greater scope of testosterone’s roles and action in human physiology. Certainly, there has been no call by academics, professional journals, the popular media or even the public to pursue, let alone fund, investigations into the role of testosterone and its benefits to society and individuals. This would contrast too sharply with the emotion-laden reactionary messages about the ethical violations of doping and challenges of high-risk youths abusing anabolic steroids that are so effective in gaining media attention and political backing.
Looking at testosterone objectively, one must admit that the illicit (illegal) distribution and use of testosterone and related anabolic-androgenic steroids (collectively called AAS) is problematic. Despite the fact that most users are socially responsible adult men who report surprisingly moderate use, regulations need to be in place to prevent and punish illicit trafficking of AAS. Failure to do so results in the administration of abusive levels by uninformed and unsupervised users, administration of the drug(s) to unsuitable candidates who may have overt or covert contraindications (obvious or undetected reasons to not be given access to AAS; i.e., pregnant women; adolescents who have not reached final height; persons with personality disorders, psychoses or neuroses; those with hormone sensitive tumors; etc.); introduction of adulterated products (drugs that do not contain the stated amount of a drug or contaminated with other drugs/chemicals), etc.
Yet, the legislation enacted latterly, in addition to the policies followed by licensure boards and protocols suggested by professional agencies have been overly restrictive, serving only to foster the “black market.” The policy of prohibition is a failed social experiment, as was shown with the 18th Amendment, which prohibited the production, sale or possession of alcohol (ethanol), later repealed by the 21st Amendment. The current state of affairs among physicians is a strong hesitancy to be involved in male hormone replacement therapy aside of treating obvious and extreme deficiency. This article addresses testosterone deficiency in men who entered adulthood with a normal testosterone status.
Conservative professional societies have published “treatment guidelines,” dictating when androgen replacement therapy is appropriate in their consensus opinion. Licensing boards, malpractice attorneys and professional liability insurance carriers rely upon these societies, trusting them to provide authoritative standards of professional practice.
Benefits and Bias
Yet, dissension exists within the ranks of physicians and scientists. The long-held position that testosterone and all related AAS are inherently dangerous to the psyche and physical health of men is challenged by a growing body of evidence. In fact, in specific examples, the dogmatic anti-androgen tact may be in direct violation of one of the principal precepts of medicine, Primum non nocere: First, do no harm.
For some reason, do no harm is interpreted to say it is better to not do anything and avoid providing benefit or avoiding harm than to act, even with the best intentions and reasonable certainty, out of fear/concern of being responsible for a harmful or undesired outcome. Absolutely, medical professionals need to consider carefully the potential risks and benefits of providing or withholding any intervention. Yet, to consider it nobler or truer to the ideals and ethics of the profession to avoid harm at the expense of not providing benefits or protection from future harm is illogical and in the opinion of many, wrong. The challenge is to have the skill and knowledge to be able to properly assess the risk-to-benefit ratio. Unfortunately, reporting bias and political pressure has retarded the growth in testosterone-related fields. This includes the propagation of inaccuracies that are treated as gospel in clinical medicine; reiteration of adverse effects present in cases of extreme abuse or with use by unsuitable candidates (adolescents or women without expressed indications); association with sports doping; and reports of criminal arrests in cases of illicit trafficking.
Testosterone therapy should never be approached cavalierly, as there are risks associated with testosterone treatment, as there is with any drug treatment. As noted above, some of the risks are overstated or incorrect: testosterone does not cause prostate cancer, clog the arteries or cause liver cancer. Testosterone can cause baldness, gynecomastia (breast development in males) and testicular atrophy (ball shrinkage). Baldness (related to the testosterone metabolite DHT) and gynecomastia (related to the testosterone metabolite E2) occur frequently in nonusers as seen in men suffering from androgenetic alopecia (male-pattern balding) and teenagers with “bitch tits.” AAS users can see an acceleration in hair loss; gynecomastia is relatively uncommon in AAS users now as effective aromatase inhibitors and estrogen receptor antagonists are available.
Gynecomastia can also be seen in testosterone deficiency, particularly in association with obesity. Testicular atrophy is a physiologic response, as the hypothalamic-pituitary-gonadal axis shuts down the testes during periods of testosterone excess. This is referred to as the negative-feedback system. This will also suppress sperm production, a factor useful in male contraceptives under development. Testicular atrophy is seen in some cases of untreated testosterone deficiency as well.
Healthier Men Have Higher T
Many have questioned whether there is any benefit to replacing or supplementing testosterone. After all, men have been aging for centuries without treatment. To ignore the benefits of testosterone is sexist and dangerous. The single “reason” for using testosterone in the eyes of the public, including most physicians, is vanity. Men use testosterone (or other AAS) just to get bigger muscles or to perform like a 20-year-old sexual super-stud. Clearly, vanity plays a role in the decision for many men, but having desirous effect does not make testosterone therapy frivolous or illegitimate. Vanity accounts for a great deal of medicine. The fields of dermatology and cosmetic surgery, cosmetic dentistry, bariatric medicine and a number of others focus on matters of image. The “industry” recognizes this, as clinics are detouring from diagnostic or therapeutic health care to provide cosmetic services.
But is the need for androgen-optimism among health care professional limited just to appeasing the vanity demands of American consumers (as is the case with so many other drugs and OTCs)? Absolutely not! Testosterone deficiency is little understood because of the trivialization and inaccuracies that have plagued the field of men’s health. Those who follow the professional literature regularly note surveys and studies that demonstrate that testosterone concentrations are negatively correlated with overall mortality risk; cardiovascular disease and mortality; cognitive loss; falls; metabolic syndrome and a host of other disease states. There is clear evidence that man is healthiest when his testosterone concentration is in the mid- to upper-limits of the physiologic range.
Extending the concentration of testosterone to the slightly supraphysiologic (above normal) range may increase the benefits seen with testosterone therapy, the risk of adverse effects may increase as well. It would appear from published clinical studies that younger men are more tolerant of higher concentrations; men of all ages appear to be able to tolerate doses of up to 300mg/week testosterone enanthate without serious short- to mid-term health consequences. Older men may develop “thick blood,” as testosterone stimulates the production of red blood cells. This can be easily monitored with a simple blood test (hematocrit). Several men in their 50s and beyond who are on prescription testosterone manage the issue by donating blood regularly; it is an elegant solution that provides a benefit to society.
If one can accept the argument that testosterone’s risk has been overstated and the benefits understated, and is concerned about avoiding the risk of morbidity and mortality that is associated with testosterone deficiency, how does one find out if he is testosterone deficient? There are a constellation of symptoms and signs associated with testosterone deficiency. Some are more strongly associated, others less so. However, these findings are nonspecific, as they can reflect other conditions. Thus, most clinicians perform a directed history and physical, along with ordering lab work, to rule out other possible causes and support the diagnosis of testosterone deficiency.
Are You A Candidate?
If a man experiences signs and symptoms of testosterone deficiency, and other relevant causes have been ruled out, is he immediately a candidate for HRT? Not always – a man may have to search for the right physician who is enlightened enough to diagnose and treat a testosterone-deficient patient. Many argue against the definition of testosterone deficiency, stating it is unwisely restrictive. Further, others argue against mandating the specified lab profile. Remember, testosterone’s actions are the result of a myriad of factors. Normal total testosterone concentration in a lab test may not reveal low free testosterone, receptor mutations, etc. There is an axiom in medicine that says, “Treat the patient, not the labs.” Teaching hospitals lecture on the dry facts involved with patient care, but also mentor the aspiring physicians on the “art” of medicine. Men showing signs of testosterone deficiency can present with “normal” testosterone concentrations by lab. This is referred to as “relative testosterone deficiency” and illustrates the need for individually assessing each patient. One longitudinal study demonstrated the broad inter-individual range of “normal” testosterone among men, as well as the value of tracking testosterone concentrations long-term to determine the relevance of a single measure in each person.
Men’s health is a field of medicine that has been and will continue to be neglected. Women have long been able to receive hormone-replacement therapy for signs of “menopause” that occur as early as the late 30s in some. Granted, there has been some controversy relating to women’s HRT, but it appears that the risks and benefits are balanced in general; also, it appears that women tolerate HRT better if they start closer to the onset of symptoms rather than waiting until they begin to suffer from bone loss, etc. Cosmetic procedures account for a large part of many practices; some carry a not insignificant risk of infection, nerve injury, even death. Low, even low-normal testosterone concentration is associated with an increased risk of morbidity and mortality; failing to address this may actually be adding to the already strained health care system. Many safe forms of testosterone replacement are available, including long-acting esters, transdermals and oral (Andriol).
The market for testosterone replacement is enormous. One estimate, using data from the Hypogonadism in Males study, claims that nearly 14 million men in the U.S. are testosterone deficient. One can only wonder if the most effective treatment (testosterone) were protected under patent, if pharmaceutical companies would exercise their potent lobbying powers to push for less stringent guidelines. Unfortunately, there is no strong advocate for men’s health. As testosterone concentrations decline, over time and with each successive generation, American men are destined to continue to suffer from the sins of omission of this nation’s leaders and caregivers.
Testosterone Deficiency: Signs and Symptoms
• Low count or absent sperm
• Reduced sexual desire (libido) and activity
• Decreased spontaneous erections
• Breast discomfort, gynecomastia
• Loss of body (axillary and pubic) hair
• Reduced need to shave
• Testicular atrophy
• Loss of height, easily broken bones
• Low bone mineral density (osteoporosis)
• Reduction in muscle strength and mass
• Hot flushes, sweats (similar to a woman’s hot flash)
• Loss of energy, motivation, initiative
• Lessened aggression, self-confidence
• Depressed mood, feeling “blue”
• Memory and concentration problems
• Sleep disturbance, fatigue, sleepiness
• Mild anemia (low red blood cell count)
• Increase in body fat or BMI
• Exercise intolerance, poor work performance
Many of the above symptoms will not manifest until testosterone reaches critically low concentration.
More information about testosterone deficiency is available from the National Institutes of Health at www.nih.gov/news-events/nih-research-matters/understanding-how-testosterone-affects-men
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