All Your Questions Answered: Testosterone Replacement Therapy (TRT) Basics

A hot topic right now is Testosterone Replacement Therapy, or TRT (See Bas Rutten’s comments in his interview with News coverage of TRT seems to be eclipsing that of anabolic steroids. The reason Testosterone Replacement Therapy is considered controversial is that its use has infiltrated combat sports, especially mixed martial arts (MMA), and many consider it a performance enhancing drug (PED). A 1996 New England Journal of Medicine article suggested that higher than normal levels of testosterone can lead to increased muscle size and mass, especially when coupled with weight training (Bhasin et al, NEJM 1996). Another study in 2003 suggested that increased testosterone increased leg muscle strength, but had no effect on endurance (Storer et al, J Clin Endocrinol Metab 2003). In professional sports, any chance to get an edge in athletic performance can, and will be, exploited.

The above studies combined with media coverage and pharmaceutical advertising has led to a misconception by many that increased testosterone is a ticket to improved athletic performance. More recent studies show that there is not necessarily a direct correlation between increased testosterone in the body and increased performance. A 2012 study of elite rugby players showed that testosterone levels measured from saliva did not correlate with results of peak force testing (Crewther et al, J Sports Med Phys Fitness. 2012). The authors further hypothesized that any results that are seen may be influenced by pre-existing strength levels. Thus, high levels of testosterone may not turn a weak man into a strong man, and even in an elite athlete, it may have no certainty of effects. Another recent study by the same authors in the same journal suggested that free testosterone levels are a strong individual predictor of squat and sprinting performance in individuals with relatively high strength levels but a poor predictor in less strong individuals.

Although this is not an exhaustive summary of the literature, it is illustrative of the concept that testosterone levels MAY improve strength performance, and any effects are probably influenced by how strong a person is to begin with. It is unlikely, given the intricacies of the endocrine (hormone) system of the body that any definitive link of increased testosterone will be found to increase athletic performance with certainty. The same arguments about anabolic steroids possibly increasing an elite athlete’s performance but not being able to turn a benchwarmer into a hall of famer will likely be used with TRT.

Testosterone and the Endocrine System

So why is the link between testosterone and athletic performance so hard to make? It’s likely because the endocrine system is a very complex system interweaving several different parts of the body secreting several different types of hormones, or chemical signals.

Testosterone Production Signalling Pathwayandrogensignaling680

When the testosterone level in the blood is low, the hypothalamus in the brain releases Gonadotropin Releasing Hormone (GnRH) which triggers cells in the front of the pituitary gland just below the brain. The pituitary gland then releases Lutenizing Hormone (LH) and Follicle-Stimulating Hormone (FSH). These two hormones then act on the testes. The LH triggers the testes to produce testosterone. Then, when the levels of testosterone reach an acceptable level, the hypothalamus senses this and stops releasing GnRH. This intricate balance of production and inhibition can be disrupted anywhere along the way, either by decreasing production of a specific hormone by one of the organs, or preventing the necessary feedback sensors of how much hormone is circulating in the blood.

Causes of Low Testosterone

While Testosterone Replacement Therapy is not generally approved for athletic competition, some athletes are given therapeutic exemptions because they have documented low levels of testosterone. The causes of the low testosterone levels, however, are varied and up to debate. There is a long laundry list of causes of low testosterone, but several of them are potentially applicable to MMA fighters or other athletes. They include anabolic steroid abuse, painkiller abuse, head trauma, and weight cutting. Of these, head trauma and weight cutting are the most controversial because they do not imply that the fighter has done anything wrong other than prepare for his match and absorb physical punishment.

Hypogonadism (low testsosterone and related diseases) caused by pituitary dysfunction after head trauma seems to be the most plausible and researched cause, as studies have been published in fairly reputable journals. Whether MMA athletes receive head trauma large enough to cause this remains a question.

Low testosterone from weight cutting or weight loss is less studied, and even those studies that have looked at it, don’t show a direct causation between weight loss and low levels of testosterone. For example, one often cited study of wrestlers competing in several bouts during a single-day tournament showed that while testosterone levels do decline below normal from the beginning of the tournament to the end, shortly after the matches the testosterone levels actually spike above normal. (Barbas et al, Eur J Appl Physiol. 2011). In addition, there is a lot more going on during a tournament than simply weight loss. Thus, it’s hard to draw a straight line from weight loss to low levels of testosterone.

Furthermore, it has been shown that a 5% – 6% weight loss for weigh-in of elite wrestlers and judo players does not affect performance (Yankanich et al, J Strength Cond Res 1998; Artioli et al, J Sports Sci 2010). On the other hand, repetitive weight loss over a complete wrestling season is associated with a reduction of strength and anaerobic performance (Kraemer et al, Med Sci Sports Exerc 2001). Thus, it is unclear if weight cutting itself directly affects performance levels, which makes it even harder to advocate for supplementing low testosterone based on weight loss.

In the general population, the rate of hypogonadism tends to be a low 2%. To TRT critics, however, it seems that the percentage of MMA fighters asking for or using TRT is much higher than the expected 2% of the population. Some people point to steroid abuse or head trauma as specific causes that may be more prevalent in the MMA population and therefore it would not be unexpected to see high levels of athletes requiring TRT. Others see an attempt to cheat the system. Certainly if a fighter has low testosterone due to steroid abuse, giving him TRT after that may seem to be compounding the athlete’s abuse of PEDs. On the other hand, if a fighter does have a medical need for TRT, denying him the right to use it or compete without it may be denying him the right to treat a medical problem, which is a basic right.


Since testosterone therapy requires a doctor’s prescription, low levels of testosterone not only have to be identified by blood tests, but the cause of the low levels needs to be pinpointed. In order to apply for a therapeutic use exemption (TUE), fighters often need to submit samples for testing of LH and FSH (to see if they are being produced at appropriate levels or are high because they are going unrecognized in the body) as well as undergo an MRI to look at the brain for sources of hypogonadism.

Many athletic commissions require fighters to be tested for overall testosterone levels, as well as something called the Testosterone to Epitestosterone ratio, or T/E ratio. When the body produces its natural testosterone, a similar compound called epitestosterone is produced in parallel, so a normal T/E ratio is considered 1:1. However, there is some documented variation in the population, such that 95% of the population falls into 4:1 and 99% falls into 6:1 (based on standard deviations). This is where many people come up with objections that fighters are allowed four or six times the normal amount of testosterone. Note that these levels are not absolute or toal testosterone levels, but ratios of testosterone to epitestosterone. This measurement becomes important because testosterone administered into the body is not usually converted to epitestosterone, so high T/E ratio may suggest that outside testosterone is circulating in the blood. It then becomes tricky to figure out if someone has a 6:1 T/E ratio due to abuse of TRT or is part of the 5% at the end of the normal bell-curve.

One test to help figure this gray area out is called Carbon Isotope Ratio Testing which can often detect if the testosterone in the body is naturally-produced or synthetic. Unfortunately, this test is very expensive and often is unaffordable for state athletic commissions to use on a regular basis.

With all of this information, it places a big burden on the athletic commissions, testing agencies, and consulting doctors to adequately work-up an athlete’s therapeutic exemption application and to ensure that fighters do not go into competition with an unfair advantage. Hopefully, by spreading information through sites like, we can make people better informed about these issues and make the sport of MMA safe for fighters with medical issues and fair for those competing in it.

*As a side note, anyone who reads scientific articles should take into consideration what journal (New England Journal of Medicine, etc) the article comes from. Not all articles and not all journals hold as much weight as others. If you are unfamiliar with the specialty area of the research, you can always look at the Impact Factor of a journal.

Jonathan Gelber, M.D. is licensed to practice medicine in the State of California.



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