Testosterone Replacement Therapy: Part One: Wonderpill or Overkill?

Recharge your vitality, handle stress, think clearer, lose fat, increase muscle AND reduce the risk of dementia(!) Gain all these benefits simply by boosting flagging testosterone levels. Sounds miraculous, right?  Manufacturers of Testosterone Replacement Therapy (TRT) are touting these advantages in direct-to-consumer campaigns aimed at middle-aged age men hoping to reclaim their mojo.

Testosterone peaks then begins to decrease around the of age 20 years, and by the time a man is 45 years old he has substantially less testosterone. Around this time he notices symptoms such as apathy, lower energy, and less drive. This phenomena is sometimes referred to as “andropause;”or “Low T.”

Optimizing hormone levels is a conventional anti-aging protocol for supporting health, but claims by TRT manufactures of renewed vigor, cognitive enhancement, and neuroprotection are astounding.

Could testosterone really be a fountain of youth? Is TRT a way to turn back time and gain both a physical and mental edge?

As a practitioner dedicated to helping people achieve optimal wellbeing at any age, I was intrigued.

The importance of testosterone in building muscle mass and reproductive behaviour is well-established in the scientific community, but could testosterone levels also influence cognition, occupational success, and brain health?

I decided to tackle the TRT claims from two perspectives: Part one takes a deep dive into the scientific research. Part two describes the ‘real-life’ experience of taking TRT from the perspective of a client on TRT for 10 years.

Before discussing the findings, let’s review the basics:  What is Testosterone?  Testosterone is a steroid hormone produced in the testicles and adrenal glands by men, and the ovaries and adrenal glands by women. Yes, women produce testosterone too but in much lower concentrations than men.

Testosterone is essential to the development of masculine characteristics for example, deeper voice, increased muscle mass, hair growth, sperm production and sexual function.

Testosterone and leadership

Increased testosterone is also associated with social dominance and competitive behaviour.  This applies to male chimpanzees competing for mating rights, wrestlers, even not-so-gladiatorial chess players;  winners have increased testosterone levels. Furthermore, the relationship between testosterone and status is bi-directional; in that “losers” show a profound drop in their testosterone levels after defeat.

How is this relevant to the world outside the Ugandan forest, wrestling ring, or chess board? Like chimpanzees, a huge part of our daily life is spent in social hierarchies: the workplace, the family, and other social groups. Undoubtedly, position and status matter; be it  Alpha chimp or CEO, those occupying high-status positions exert a huge influence over group members.

Thus, in accordance with primatology research, it is plausible that testosterone is associated with higher social status in the workplace?  If so, could testosterone be a biological marker of leadership and social status?

In a recent Harvard study, researchers attempted to find out if there was a hormonal profile associated with social status in the workplace. They recruited male executives from the public sector (including Military, Law enforcement and Government), measured testosterone and cortisol, and as a determinant of social status, recorded the number of subordinates they managed.  Variables such as age, education, years experience, and income were controlled for.

Initial analysis found no significant relationship between testosterone and social status, suggesting testosterone levels alone do not predict leadership status. However, a significant interaction between testosterone, cortisol and social status was discovered. Specifically, the hormonal profile of high testosterone in combination with low cortisol was a significant predictor of high social status.

Why might cortisol be important? Cortisol is a stress hormone, it is also an antagonist to testosterone. Cortisol has been found to inhibit motivational impact of testosterone. Consequently, when high stress is experienced,  testosterone decreases, and the competitive drive is impaired. (Theoretically, it’s why watching competitive sports such as hockey is a legitimate stress reduction technique for men, because it would increase testosterone and decrease cortisol.)

The researchers from the leadership study posit this high-testosterone and low-cortisol combination is found in high status leaders because low-cortisol high-testosterone individuals  manage stress better, while at the same time:  “are prone to [stereotypical] leadership behaviours such as proactive, bold actions, which depend on some inclination toward risk and aggressiveness…..[It is] these behaviors that facilitate promotion to powerful managerial positions”.

However, as fascinating as these finding are, can they be applied to all leadership and social status situations? Leadership is a broad concept, and it could be argued that the military and law enforcement, with a clearly defined chain of command is inclined to a more authoritarian and competitive style of leadership.  Accordingly, it makes sense such a hierarchy would lend itself to the testosterone driven ‘challenge hypothesis’, where bold actions are rewarded with promotion.

In contrast, such a hormone profile may not apply to managers in more egalitarian companies where prestige, emotional intelligence, and cooperation is the currency for social status and leadership.

Furthermore, like many studies investigating the effects of testosterone, the study is androcentric.  Women also occupy high status executive positions, and the assumption female leaders have a similar hormonal profile to men remains conjecture.

Testosterone and Reasoning

It can be agreed that despite the nuances of what defines social status in a corporation, a key component of success at work (and in life) depends on our ability to use our brain effectively.  Testosterone has been found to affect cognitive abilities but whether this is a help or a hindrance is subject to debate.

Take for example, “confidence”: What’s wrong with being confident? Well nothing but what about when you’re wrong?

Research comparing undergraduate students’ actual exam performance with their perceived performance found men and women were equally confident of their judgements for correct answers. However, men were more confident they had answered correctly even when they were wrong.

Similarly, other studies have found compared to women, men are more overconfident about their ability and intelligence. Men are more likely to rate themselves as above average intelligence, and believe their solutions to problems and performance is better than others.  Men are also less likely to incorporate opinions of others once they have made a decision (insert your own politically inappropriate wifey joke or mansplaining anecdote…).

Gender differences are also found in higher-order cognitive processes such as decision making and judgment. Psychologists have consistently found females are more risk-aversive than males across a broad range of behaviours. In general men are more likely to take greater financial risks, engage in more dangerous activities, and tend to make more impulsive decisions than women.

Can testosterone account for this discrepancy in behaviour?  Undeniably, not all gender differences in cognitive behaviour can be accounted for by sex hormones. Cultural, psychological and social influences exert a huge effect, and it is beyond the scope of this article to explore the complex nuances of gender studies.

However, evidence from neuroscience, endocrinology, and neuroeconomics (yes, that’s a research field) does substantiate the claim that testosterone, not gender is responsible for risk-taking, impulsivity, and ego-centric decision-making.

In one of the largest double-blind studies on testosterone, researchers from Wharton business school examined the effect of testosterone on decision making.  243 men were given either testosterone gel or a placebo, and completed the cognitive reflection test (CRT).

The CRT is a test designed to assess a person’s ability to override an incorrect knee-jerk response, and engage in further reflection to find the correct answer.

An example of the CRT question is:  “In a lake, there is a patch of lily pads. Every day, the patch doubles in size. If it takes 48 days for the patch to cover the entire lake, how long would it take for the patch to cover half of the lake?”  The gut reaction is to say 24 days, yes? That would be wrong. If we suppress the impulsive answer, and think it through logically, then the answer is 47 days. (If you’re not sure why this is the answer email me and I’ll explain. Or Google it.)

How did the men in the testosterone study do? Compared to placebo, men who were given testosterone were 35% more likely to give the wrong (knee-jerk) answer, gave this answer faster, and were more likely to believe this was the correct answer.  This effect remained even when the researchers took into account mood and math ability.  In other words, testosterone appeared to reduce the capacity to override impulsivity and think things through more analytically.

What are the implications of these results beyond getting the answers to some “trick” questions wrong in a psychology lab?  The researchers conducted a real-world experiment this time giving male stock-traders either testosterone gel or placebo and comparing performance on a stock market simulation.

They found the men with boosted testosterone significantly overpriced assets compared with the placebo, and they were slower to integrate data about falling values into their trading decisions. In other words, they “created a trading bubble that was slow to pop.”

Disturbingly, this trend has been found in actual financial markets. Neuroscientists from Cambridge University, England, measured testosterone and cortisol levels in a group of young male traders working at the London Stock exchange. They found higher testosterone was related to overpricing, risk and higher profits, whereas, in contrast high cortisol was related to risk aversion. Both situations impair rational decision-making.

They postulate that financial bubbles occur due to high testosterone artificially increasing risk, followed by cortisol increasing risk aversion, and in turn exaggerating the downward movement of the market.

It begs the questions could such a hormone-induced wave cycle in part account for the errors of judgment in the recent boom and bust financial crises?

Testosterone on the brain

Why does testosterone exert an effect on risk-taking, impulsivity and overconfident decisions? Testosterone influences neural pathways in the brain in a number of ways.  Perhaps the most notable is the orbitofrontal cortext (OFC) a region of brain associated with self-evaluation and impulse control. When the OFC is active it functions somewhat like a sensible inner-guide.

Brain-imaging studies have found that testosterone is negatively correlated with activity in OFC. In other words, testosterone seems to silence the inner guide that tells us to be less impetuous.

Testosterone also has neurological rewarding and addictive properties because it increases the neurotransmitter dopamine in the nucleus accumbens, a brain region found to be stimulated in anticipation of irrational risk seeking.  It could be that high testosterone and dopamine levels increase the thrill of pushing limits and taking risks. (For a detailed review on the role of neurotransmitters see the following post: Neuroscience of leadership).

Additionally, testosterone disrupts human collaboration by increasing egocentric choices.  (Good Advice you just can’t take?) This might explain why the male traders were slow to incorporate data in their decisions, and why other studies have found men ignore, or minimise input from other group members in making their judgment.

This ego-centric thinking in decision-making was also found in women given testosterone compared with women given a placebo, suggesting testosterone rather than gender is more important in explaining single-minded judgements.

These research findings present a cautionary tale of elevated testosterone but is decisiveness and acting on impulse really such a bad thing? I would argue, No. Acting on impulse or “going with the gut” can mean survival in many cases.

Decisiveness is also a good thing. Having the confidence to take action when the outcome is unclear is a keystone for the success of many entrepreneurs. In response to a tough question about Apple’s disappointing performance, CEO Steve Jobs highlighted the importance of taking decisions, even if they led to mistakes, as a way to move forward. Given the huge success of Apple Inc. under Steve Jobs it would appear having a single-minded vision combined with an ability to take risks paid off.

Problems arise in situations where life or death is a real outcome in the decision-making process, such as the overconfident surgeon, or military commander. In such situations extra checks and balances such input from other sources, and risk assessment should be encouraged.

Testosterone and dementia

So far we have considered the effects of Testosterone on younger men.  It would appear that testosterone influences decision-making, increases motivation, and drive.  However, testosterone it is not a static hormone: levels fluctuate depending on many variables including time of day, presence of either attractive or threatening individuals, and stress.

What about the claim by TRT manufacturers that testosterone protects against dementia?

The scientific evidence is inconclusive. Longitudinal studies on men (not undergoing TRT)  have found a relationship between high testosterone levels and reduced risk of Alzheimer’s Disease. However, promising as this sounds, it does not imply causation, but rather implies low testosterone might be a risk factor for developing dementia.

A logical proposition to these findings is the question: would supplementary testosterone (TRT) reduce cognitive decline and improve cognitive function?

Unfortunately, large randomized controlled studies, including two long-term studies from the Testosterone Trials cited in the JAMA failed to find any evidence that testosterone supplementation improves memory or cognitive function.

One study found that testosterone supplementation in elderly men diagnosed with mild cognitive impairment (MCI) modestly improved spatial memory and verbal memory but did not significantly improve other areas of cognition.

However, it is important to note that administering testosterone also naturally increases estrogen levels.  To ascertain if this effect was due to testosterone or the interaction between estrogen and testosterone, the researchers gave half the group an estrogen blocker.

They found spatial memory but not verbal memory improved. This suggests that a balance of both testosterone and estrogen is important for different cognitive functions.

Nonetheless, the lack of clinical improvement in other areas of cognition would suggesting that TRT is not an effective treatment for cognitive decline.

 Conclusion: Does TRT offer Hope or Hype?

In terms of improving cognition, the scientific evidence would suggest testosterone is not the anti-aging cure advertisers claim. In fact, it could be argued that supplementing testosterone in individuals who already have high levels may lead to more irrational and risky decision making.

Physical Benefits including improved fitness, increased muscle mass, weight loss, better sexual function, and better sleep have been documented in research. It could be these factors that indirectly increase in psychological wellbeing and improved mood.

While having low testosterone is a risk factor for dementia, there is no evidence to suggest that supplementing with TRT will reduce cognitive decline.

It would seem that TRT alone may not be the magic bullet to anti-aging. However, what may be more promising is retaining Testosterone levels through a healthy lifestyle protocol.

To conclude my exploration of the effects of Testosterone, I wanted to go beyond the lab and understand the experience from the point of view of someone who took the decision to have TRT. I  wondered what effect does supplementary testosterone have on cognitive function in middle aged men in everyday life?

I reached out to  A.J. who graciously agreed to share his story. Read more here: part two

References:

Beer, J. S., Lombardo, M. V., & Bhanji, J. P. (2010). Roles of Medial Prefrontal Cortex and Orbitofrontal Cortex in Self-evaluation. Journal of Cognitive Neuroscience, 22(9), 2108–2119. http://doi.org/10.1162/jocn.2009.21359

Byrnes, J. P., Miller, D. C., & Schafer, W. D. (1999). Gender differences in risk taking: a meta-analysis. Psychological Bulletin, 125, 367–383.

Cross, C. P., Copping, L. T., & Campbell, A. (2011). Sex differences in impulsivity: A meta-analysis. Psychological Bulletin, 137(1), 97-130.

Frye, C. A., Rhodes, M. E., Rosellini, R., and Svare, B. (2002). The nucleus accumbens as a site of action for rewarding properties of testosterone and its 5alpha-reduced metabolites. Pharmacol. Biochem. Behav. 74, 119–127.

Wright, N. D., Bahrami, B., Johnson, E., Di Malta, G., Rees, G., Frith, C. D., & Dolan, R. J. (2012). Testosterone disrupts human collaboration by increasing egocentric choices. Proceedings of the Royal Society B: Biological Sciences, 279(1736), 2275–2280. http://doi.org/10.1098/rspb.2011.2523

Lundeberg, M. A., Fox, P. W., & Punćcohaŕ, J. (1994). Highly confident but wrong: Gender differences and similarities in confidence judgments. Journal of Educational Psychology, 86(1), 114-121.

Mehta, P. H., & Beer, J. (2010). Neural mechanisms of the testosterone-aggression relation: The role of orbitofrontal cortex. Journal of Cognitive Neuroscience, 22(10), 2357-2368. DOI: 10.1162/jocn.2009.21389

Ring, P., Neyse, L., David-Barett, T., & Schmidt, U. (2016). Gender Differences in Performance Predictions: Evidence from the Cognitive Reflection Test. Frontiers in Psychology, 7, 1680. http://doi.org/10.3389/fpsyg.2016.01680

Healy A., Pate J. G. (2007). Overconfidence, Social Groups, and Gender: Evidence from the Lab and Field. Available at: https://ssrn.com/abstract=934320.

Johnson D. D., Fowler J. H. (2011). The evolution of overconfidence. Nature 477 317–320. 10.1038/nature10384

Basaria  S, Coviello  AD, Travison  TG,  et al.  Adverse events associated with testosterone administration.  N Engl J Med. 2010;363(2):109-122.

Stanworth, R. D., & Jones, T. H. (2008). Testosterone for the aging male; current evidence and recommended practice . Clinical Interventions in Aging, 3(1), 25–44.

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