Submitted by: Mr. P.J. Vanny1*, Dr. Jordan Moon2*.
1* P.J. Vanni, M.S., NSCA-CPT
2* MusclePharm Sports Science Center Research Institute Director, Distance Learning Faculty member, Department of Sports Exercise Science, United States Sports Academy.
P.J. Vanni is a third year Sports Management Doctorate Student at the United States Sports Academy, an Independent Distributor for Advocare Nutrition Company, and is also a faculty member in the Health and Physical Education Department at The Haverford School in Haverford, PA.
Dr. Jordan Moon is the MusclePharm Sports Science Center Research Institute Director, as well as a Distance Learning Faculty member for the Department of Sports Exercise Science at The United States Sports Academy.
Introduction
The emergence of testosterone (Te) use in sports has increased drastically since its inception, spawning a “cat and mouse game” between athletes and regulating bodies. Once a means for detection is developed, scientists are developing new forms or compounds of Te which are undetected by current testing or mask increased Te in some way to make the testing inefficient.
Athletes that can improve their level of play through supraphysiological doses of Te are willing to risk getting caught because they believe the pros outweigh the cons (20). If an athlete can avoid getting caught using Te, the benefits to their performance can include notoriety, increased individual and possibly team success, and increased salaries.
The endocrinology of Te release is based on homeostatic regulations. A human will release Te based on the need to grow as during infancy and puberty, and based on exercise demands explained in the proceeding research. Increasing the amount of Te in the body will have an increased effect on the already potent and beneficial outcomes of natural Te.
As you will see in this review, the effects of Te use in athletes can improve their physical strength, stature, and possibly performance. Much research has proven the effects of Te doping on an individual, whether they are an athlete or not; although, these benefits do not ensure success in certain sports. This review will discuss the endocrinology and origins of Te, the physiology behind how Te works, the effects, the relationships of these effects to sports, the ethics of Te use in sports, and the relationship between Te and sports related skills.
Keywords: testosterone, supraphysiological doses, Te
Endocrinology
The endocrine system controls the production and regulation of Te in the body through a gland known as the gonads. The gonads are ovaries in females and testes in males. In women, the ovaries are located in the pelvic cavity lateral and superior to the uterus. The ovaries produce two hormones: progesterone which supports a developing fetus during pregnancy, and estrogens which stimulate puberty and trigger the development of female secondary sex characteristics, bone growth, and height changes during adolescence.
The testes are found in the scrotum of males and produce Te. The amount of Te synthesized is regulated by the chain between the hypothalamus gland, pituitary gland, and testes.When Te levels are low or when puberty triggers an increased release, gonadotropin-releasing hormone (GnRH) is released by the hypothalamus, which stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH), stimulating ovaries in females and testes in males to synthesize Te. This chain also works as a regulating feedback. As there are increasing levels of Te, this will trigger the hypothalamus and pituitary to inhibit the release of GnRH and FSH and LH.
Physiology of Testosterone
There are two main ways in which Te brings about its effects on the body. The first is by directly activating an androgen receptor and the other is by converting to estradiol, then activating androgen receptors (33). In body tissues, Te is transported into the cytoplasm of tissue cells where it binds with androgen receptors. Te can also be broken down in the cytoplasm to dihydrotestosterone (DHT). This DHT will bind to the androgen receptors with five times more potency than Te binding. This bonded receptor moves into the cell nucleus and binds with nucleotide of chromosomal DNA (33). This bonding influences transcriptional activities, producing the androgen effects.
In the bones, the converted estradiol promotes ossification of cartilage into bone, which in turn will close epiphyses and bone growth will cease. In the central nervous system, testosterone is again converted to estradiol. Estradiol, not Te, serves as a vital feedback signal to the hypothalamus, especially affecting LH secretion and regulation.
Te is the primary androgen in males, which means it is a substance that maintains and stimulates male development. During puberty, Te levels spike and are responsible for many changes, transitioning a boy into a man. These changes include: development of male sex organs, growth of facial and body hair, deepening of the voice, increase in height, and increase in muscle mass. Beyond puberty, Te is responsible for maintaining multiple functions in the body which include maintaining libido, sperm production, maintaining muscle mass and strength, and promoting healthy bone density.
LITERATURE REVIEW
History of Use in Sports
Athletes have used many different performance enhancing drugs (PED), dating back to the 19th century in Olympic and professional sports. Even today with the detection tests that have been developed, there are still instances of athletes testing positive in Olympic, professional, collegiate, and even high school sports. A 2002 review on the History of doping by Yesalis and Bahrke (34) highlighted the use of Te as an anabolic steroid. The authors suggested that the age of anabolic use began with Charles Edouard Brown-Sequard, who self administered injections that contained blood of the testicular veins, semen, and juice extracted from a testicle of a dog or guinea pig. Brown-Sequard described the effects as improvements in physical and mental energy (7). After Brown-Sequard had taken a month off of the injections, he returned to a prior state of weakness. Even though many attribute his benefits as the placebo effect, Brown-Sequard established the value of hormone replacement or supplementation therapy. This report spawned experiments throughout the Western world involving testicular extracts.
The use of these testicular extracts in athletics came soon after Brown-Sequard’s (7) report. In an 1896 paper by Zoth (35), he states that “The training of athletes offers an opportunity for further research in this area and for a practical assessment of our experimental results.” This served as a prophecy of the future of anabolic steroids in the 20th Century as transplantation of human and animal testicular material became popular to cure or “rejuvenate” (13, 14). In 1935 this practice ceased as scientists were able to isolate, chemically characterize, and synthesize the hormone Te and reveal the basic nature of its anabolic effects. Shortly after, oral and injectable Te was available to the medical community.
In 1936 it was rumored that the Germans supplemented Te before the 1936 Olympics, although no proof was found due to the lack of research on Te having an ergogenic effect on humans (10). Wade (29) alleged that during World War II, German soldiers took Te before battle to increase aggressiveness. This claim has yet to be documented and contradicts the belief that the Nazis were opposed to organism-altering drugs. In the 1950s, reports of West Coast bodybuilders using Te for better physique surfaced (32). Since then, bodybuilding has had strong ties to TE and anabolic use (34).
The first reports of Te use in sports came from the reports that the Soviet weightlifting team had used anabolic steroids in the 1950s. Dr. John Ziegler claimed that the Soviet counterpart actually told him they were taking Te (34). Dr. Ziegler then experimented with Te on himself and a few other weightlifters at the York Barbell Club. After some of the weightlifters Dr. Ziegler was working with achieved championship status, news of the efficiency of this Te usage spread to other strength-intensive sports in the 1960s. Because anabolic use became so prevalent, urine testing was initiated in the Olympics in 1968 (18). By 1969 athletes were openly praising the effects of Te and anabolic steroids publicly (8).
The use of Te and anabolic steroids became widespread in Olympic and professional
sports through the 1970s and 1980s (18), so much that the NFL adapted urine testing in 1987. In 1990, the Anabolic Steroid Act was published and usage required a prescription from a physician. This act and the Dietary Supplement Health and Education Act in 1994 have deterred athletes from illegal anabolic steroids to legal nutritional supplements (18).
In Bowers’ article (6), he points out that “the availability of numerous synthetic steroids and recombinant peptide hormones has made testing an analytical challenge.” Due to testing, scientists searched for new compounds and synthetics that can go undetected and still bring forth the same results. A very popular example of this was the case of the Bay Area Laboratory Co-Operative (BALCO). BALCO had developed a cream which contained both Te and epitestosterone; a ratio of the two hormones was used in testing (27). The administration of both of these hormones caused inefficient data and results in the drug testing procedures of that time. The discovery of these compounds and their use in baseball led to the January 2005 changes in MLB’s steroid testing and sanctions policy. As new testing has been developed, the International Olympic Committee and all professional sports leagues have issued banned substance lists and adopted the most recent testing procedures to ensure fair play among the athletes (28).
Physiological Effects Related to Sports
In 2006, Giannoulis et al. (11) investigated the effects of growth hormone and/or Te in healthy elderly men. This six month double-blind study consisted of men ages 65-80 grouped into 4 areas: 1) Placebo GH and Te, 2) GH and placebo Te, 3) placebo GH and Te, or 4) GH and Te. The results of this study were administration of both GH and Te in older men had more positive effects than the other groups, including increased lean body mass (P = 0.008), muscle size (P = 0.006), and aerobic capacity (P < 0.001). Notably, lean body mass did increase with GH administration only as compared to placebo group.
In 2009, Sattler et al. (24) performed a similar investigation to Giannolis et al. (11), testing the effects of GH and Te administration on elderly men. The sample size in this study was 122, significantly higher than Giannolis et al. (11), and the methods were slightly different. All subjects received administration of Te on two tiers, one getting 5g/day, and the other getting 10g/day. The subjects again were placed into three tiers for each initial group (six total). The three tiers received administration of GH at 0g/day, 3g/day, and 5g/day. Sattler et al. (24) investigated the effects of administration on body composition, muscle strength, aerobic capacity, and hormone assays. The results of this study showed increases in lean body mass (P < 0.008), maximal muscle strength (P < 0.008), and aerobic endurance (P < 0.008), and total fat mass decreased for all groups (P = 0.0002). Sattler’s et al. (24) conclusions are that supplemental Te produced significant gains in total and appendicular lean mass, muscle strength, and aerobic endurance with significant reductions in whole-body and trunk fat. Outcomes appeared to be further enhanced with GH supplementation. These conclusions back Giannolis’ (11) findings in 2006 regarding GH and Te supplementation in older men.
In 1996, Bhasin et al. (3) experimented with the effects of just Te supplementation in normal men. There were 43 normal men that took part in the study, and were assigned to one of four groups: placebo with no exercise, Te with no exercise, placebo plus exercise, and Te plus exercise. The subjects received injections of either 600mg of Te or placebo weekly for 10 weeks. Subjects in the exercise group took part in a normal routine three times per week, and all were measured for fat-free mass, muscle size, and strength before and after the 10 weeks. In the two no-exercise groups, the group receiving doses of Te showed increases in muscular size and strength (P<0.05). The Te and exercise group showed increases in fat-free mass, muscle size and strength in comparison to all other groups (P<0.05). Bhasin et al. (3) concluded that supraphysiologic doses of Te, especially when combined with strength training, increase fat-free mass, muscle size, and strength in normal men.
In 2002, Bhasin, Woodhouse, and Storer (4) backed Bhasin et al. (3) by publishing a review on the proof of the effect of Te on skeletal muscle. The authors report that abuse of Te by those who use Te supplementation, are based on the assertion that it will help increase muscle mass and improve skeletal muscle performance, effects that will translate into improvements in athletic performance. Among other effects of Te listed in this review that are not pertinent to sports, Bhasin, Woodhouse, and Storer (4) do highlight body composition, muscle strength, fat metabolism, and athletic performance which will be discussed in a later section.
Three different studies, not including Bhasin et al. (3) were mentioned as to the effects of Te on muscular strength and body composition. Collectively the data from the studies conclude that supraphysiological doses of Te produce increases in fat-free mass and strength in men. The authors also report that strength training in conjunction with Te supplementation may augment the effects of androgen on the muscle (3, 31).
Long term studies of Te supplementation report a consistency in the reduction of fat mass, and epidemiological studies have shown serum Te levels are lower in middle-aged men with visceral obesity. Research shows there is an inverse relationship between serum Te levels and visceral fat in men (16, 17) and that Te is important in fat metabolism and regional fat distribution in men (17). Kadi (15) backed these results and reported “testosterone administration in sports provides an unfair muscular advantage over non-drug users. The long-term consequences of the heavy recruitment of satellite cells on their proliferative potential and the regenerative capacity of skeletal muscle are unknown” (15).
In 2006, Cardinale and Stone (9) studied the effect of Te on explosive performance, an attribute that can be utilized in many sports. Seventy elite athletes (22 women and 48 men) in track and field (sprinters), handball, volleyball, and soccer competing at national and international levels participated in the study. The idea was to compare resting Te levels and vertical jumping ability in elite men and women athletes. The results showed that resting Te levels in women were roughly 90% lower than men (P<0.001), and men’s vertical jump was 16% higher than women (P<0.001). It was noted that when maximal lower body strength is adjusted for fat-free mass or body mass, women are as strong as men. Therefore the positive relationship identified between Te levels and vertical-jumping ability (P<0.001) supports the idea that Te plays an important role in neuromuscular function, in this case power movements. This article gives yet another positive effect and another reason behind athlete’s use of Te supplementation. Meinhardt et al. (19) supported the results of Cardinale and Stone (9) in regards to body composition and physical performance, but the participants of this study included 96 recreationally trained athletes of both sexes.
Haddad et al.’s (12) meta-analysis that assessed the effect of testosterone use on cardiovascular events and risk factors in men reported that any available evidence weakly supports the conclusion that Te use in men is not associated with cardiovascular effects. Therefore, users of Te should be cautioned on the possible long-term cardiovascular risks that may be linked to, and not yet observed, this supplementation (12, 26). Also Basaria et al. (2) supports Haddad et al. by reporting that the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events in his study.
Psychological Effects Related to Sports
For many years it has been accepted that along with the physiological effects of testosterone, there are obvious psychological effects that explain moods and behaviors in human users. The notion of “roid rage” has given an excuse to certain behaviors and crimes of those who ironically have been supplementing with Te or other steroids. As you will see, the research has caused quite a controversy.
In 1994, Bjorkqvist, Nygren, Bjorklund, and Bjorkqvist (5) experimented with Te intake and its effects on aggression. In this double-blind study, 27 men were either given 40mg of Te, a placebo, or nothing every day for one week. The results revealed a significant placebo effect. At the end of the week, the placebo group scored higher than the Te and the control group on self-animated anger, irritation, impulsivity, and frustration (P<0.01). An explanation behind this may be the lack of natural Te in the Te group due to homeostatic suppression of release. The authors further point out that these results suggest that androgen use causes expectations, rather than actual increases in aggressiveness (5).
In 1996, another double-blind 10-week study was conducted, this time they increased the dosage of Te to 600mg per week and included exercise into specific groups (25). Forty-three men ages 19-40 were assigned into four different groups: placebo no exercise, Te no exercise, placebo plus exercise, and Te plus exercise. The Multi-Dimensional Anger Inventory, which includes five different dimensions of anger (inward anger, outward anger, anger arousal, hostile outlook, and anger eliciting situations), and a Mood Inventory were completed at the end of the study. At the conclusion, no differences were observed between exercising and non-exercising and between placebo and Te treated subjects. These findings back Bjorkqvist et al. (24) in that supraphysiological doses of testosterone, when administered to normal men in a controlled setting, do not increase angry behavior (24).
In 2000, Pope, Kouri, and Hudson (23) performed a similar study with somewhat different results conflicting the previous two articles. This study consisted of 56 men in a randomized, placebo controlled experiment. All subjects were given doses rising to 600 mg/wk and placebo for six weeks, separated by six weeks of no treatment. Psychiatric measures included Young Mania Rating Scale, the Point Subtraction Aggression Paradigm, the Aggression Questionnaire of Buss and Perry, the Symptom Checklist-90-R, daily diaries of manic and depressive symptoms, and similar weekly diaries completed by a significant other who knew the participant well. Results showed that testosterone treatment significantly increased manic scores on the Young Mania Rating Scale (P=0.002), manic scores on daily diaries (P=0.003), and aggressive responses on the Point Subtraction Aggression Paradigm (P=0.03). Pope et al. did point out that the effects, were not uniform across individuals; most showed little psychological change, and a few developed prominent effects (23).
O’Connor, Archer, Hair, and Wu (21) experimented with the effects of Te on cognitive function in men. This study consisted of a single-blind placebo-controlled design involving 30 healthy men and seven hypogonadal men. The healthy men were placed into two groups, one receiving 200mg Te weekly for eight weeks, the other receiving 200mg sodium chloride weekly for eight weeks. The hypogonadal group received the physiological replacement dose of 200 mg of Te bi-weekly for eight weeks. All groups underwent a battery of neurophysiological tests and had Te measured at start, four weeks, and eight weeks into testing. Results showed that at week four, the Te group showed decreases in spatial abilities compared to placebo (P<0.01) and performed significantly better than the placebo group in the measure of verbal fluency (P<0.01). No significant changes were found on any other tests. These results suggest that Te supplementation inhibits spatial ability and increases verbal fluency (21).
O’Connor, Archer, Hair, and Wu (21) again experimented with the effects of Te in 2004, this time studying mood, aggression, and sexual behavior in young men. This double-blind placebo-controlled study grouped 28 men into one of two treatment groups which varied the timing of Te injection. The injection consisted of 1000mg of Te undecanoate, which was a new, long-acting concentration. Mood, self and partner-reported physical and verbal aggression, anger, hostility, irritability, assertiveness, self-esteem, and sexual function were assessed. The results of this research stated that increased circulating Te was associated with significant increases in anger-hostility from baseline (P<0.05), and Te treatment did not increase aggressive behavior or induce any changes in non-aggressive or sexual behavior (P<0.05). These results suggest that supraphysiologic-induced elevation of circulating Te, to the range likely to be used in hormonal male contraception, has limited psychological effects.
CONCLUSION
Te use in sport has given researchers plenty of targeted substance matter and fueled much controversy for over a century. The history of Te started with self-administration of gonadal material by researcher Charles Edouard Brown-Sequard and has been linked to Nazi soldier’s use during wartime to increase aggressiveness, and of course has become extremely popular in bodybuilding and sports.
Abundant research has shown the physiological effects of Te use: increased muscle size and strength, aerobic endurance, decreased fat mass, faster recovery from high exertion exercise, and increased muscular power. These effects can translate individually or in combinations to assist athletes in nearly every sport. The issue researchers have had was the amount of a dosage that should be used and how frequently a dose should be taken. Increased doses have shown better potential in enhancing these pre-mentioned effects, but the extent of any damage done to the body from long-term usage has yet to be solidified. Whether the pros outweigh the cons is an individual decision that may be based on individual morals, goals, fears, or ambitions.
Athletes seek advantages for performance enhancement. The term “performance enhancement” includes items such as equipment, sneakers, coaches, technology, pharmacology, endocrinology, and nutrition. Stronger, bigger, faster muscles promote confidence in physical ability which may contribute to changes in mood, including aggression, anger, and frustration. Exaggerated psychological effects of Te use were further highlighted in Sports Illustrated by Lyle Alzado (1), attributing the aggressive level of play and (his) brain tumors to steroid use. The extent is unclear as to how Te affects coordination, reaction, intelligence, manipulation and spontaneity, adaptation, and injury prevention. Future Te research may investigate safety considerations and the performance advantages and disadvantages of long term use.
APPLICATIONS IN SPORT
Over a century of Te supplementation/administration research has shown the effectiveness in humans. Positive effects can directly translate to improving or enhancing the physical requirements necessary for the successful participation in sports. The inclusion of Te administration into any training program should give the user a definitive edge over an athlete who is not administering Te. Performance may be affected to benefit the user at the risk of the consequences of being caught using this banned substance. Furthermore, there are known and unknown as well as short and long term risks of receiving Te to raise Te to normal levels as well as taking superphysiological amounts of Te. Athletes need to consult their physician if they are thinking about taking Te in any capacity and also need to consider the unknown and known health risks and the possibility of being banned from their sport for life.
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