Also known as the male sex hormone, testosterone is one of the steroid hormones found in the human body. In men, it is secreted from the Leydig cells in the testes, and the adrenal glands, and in women it is produced by the ovaries. This hormone is primarily responsible for creating masculinity in men. It not only helps the reproductive features develop in men, but also helps keep them healthy by maintaining strength and preventing certain diseases like osteoporosis.
Being a steroid hormone, it also has the anabolic and androgenic effects that other steroids do. Its anabolic effects include increase of muscle mass and bone density, linear growth in the body, and bone maturation. Its androgenic effects include maturity of the male reproductive organs, deepening of voice and growth of axillary hair.
History of Testosterone
When Arnold Adolph Berthold first performed castration and transplantation of testicles in fowls, he linked a testicular action to the circulating blood. When Charles-Édouard Brown-Séquard (a professor of the Harvard University) injected himself with a “rejuvenating elixir”, the research on testosterone found new enthusiasm. This elixir consisted of an extract of the testicles of dogs and guinea pigs. In the report that he published in The Lancet, he said that after taking the elixir, his vigor and vitality felt wonderful, but only lasted for a very short time. For this reason, he felt disappointed in the research, and quit doing it.
Many years later, in 1927, Fred C. Koch – a professor of Physiologic Chemistry in the University of Chicago – found a large supply of cow testicles in the stockyards of Chicago, and gathered willing students to extract the isolates. The same year, together with a student (Lemuel McGee), he created a compound which remasculinized castrated animals if they were injected with it.
A few years later, Ernst Laqueur group in Amsterdam also extracted testosterone from the testicles of cows in the similar manner, but serious studies on testosterone in the human body only began in the 1930s when the pharmaceutical giants Ciba (Switzerland), Organon (Netherlands) and Schering (Germany) began their full scale researches.
The name “testosterone” was coined by Organon, who was also the first to isolate the hormone in 1935. Adolf Butenandt, a chemist from Schering, worked out the structure of the hormone. Later that year, together with another chemist Hanisch, Butenandt chemically synthesized testosterone from cholesterol. Just one week later, A. Wettstein and Leopold Ruzicka – chemists in Ciba – also independently synthesized testosterone in a similar manner and published their discovery. Through this discovery, both Butenandt and Ruzicka received a joint Nobel Prize in chemistry in the year 1939.
From the earlier incomplete syntheses of testosterone esters (in the researches that were done in the 1930s), Murlin and Kochakian showed that testosterone increased nitrogen retention in animals. Nitrogen is essential for anabolic activities. After this discovery, Allan Kenyon and his group showed both the anabolic as well as the androgenic effects of testosterone in women, boys, and eunuch-like men.
After this, the period from the 1930s to the 1950s came to be known as the “Golden Age of Steroid Chemistry”. During this period, the researches progressed quickly, and many new discoveries were made. The main thing that was proved in these researches was that testosterone, and compounds related to it, had the potential of increasing the strength, muscle, health and well-being of people who used them.
Production of Testosterone in the Human Body
Testosterone is primarily created in males by the Leydig cells in the testes. This creation is regulated by a hormone cycle known as the Hypothalamic-Pituitary-Testicular Axis, or the HPTA in short. This cycle runs as follows. The hypothalamus detects the level of testosterone in the body, and when it falls below a certain level, the hypothalamus secretes the gonadotropin releasing hormone (GnRH). This hormone in turn stimulates the pituitary gland to release the follicle stimulating hormone (FSH) and the luteinizing hormone (LH). These hormones then stimulate the testicles to produce testosterone. LH controls the Leydig cells and the amount of testosterone produced by them.
When the testosterone levels rise above a certain level, the hypothalamus stops secreting GnRH. This in turn stimulates the pituitary gland to stop the production of FSH and LH. As a result, the production of testosterone stops till its levels fall below the required level again. This response of high testosterone levels to the hypothalamus is also known as the negative feedback loop. The cycle is required to maintain homeostasis, or a balanced level of testosterone, in the body.
When a hormone is produced in one part of the body, it travels to the rest of the body parts through the bloodstream, by binding itself to a carrier protein in the blood. In case of testosterone, the carrier protein is called the Sex Hormone Binding Globulin or SHBG for short. However, when testosterone is travelling throughout the body in this bound form, it cannot take part in any reactions, and as such, is useless for all purposes. It cannot play any active role. Only the freely circulating testosterone can have any anabolic or androgenic effect at all. In case SHBG levels increase, active testosterone amounts in the blood will decrease.
Physiological effects of Testosterone
Testosterone affects a human body throughout its life, right from conception to adulthood. Within 4 to 6 weeks of conception, testosterone develops characteristics like seminal vesicles and genital virilization features like phallic urethra, phallic enlargement and scrotal thinning. After birth, during the first few months, the testosterone levels in a male infant remain as high as in a boy at puberty. But after that, it comes down to barely detectable levels. It is believed that this high level of testosterone causes the masculinization of the male brain.
Testosterone is also responsible for the quality and speed of the growth of muscle tissue as well as its strength in men. It is also responsible for much of the brain activity, like memory and learning skills. The energy levels required for the proper functioning of physical activities is also regulated by this hormone.
During puberty, testosterone causes physiological changes like change of voice pitch, change of body odor, growth of pubic hair, and bone maturation. It also causes changes like increase in muscle mass and strength, appearance of Adam’s apple, loss of subcutaneous fat in the face. During adulthood, testosterone levels account for many functions like sperm development, regulation of physical energy and muscle trophism, but the levels of testosterone decline in the later years of adulthood.
Role of Testosterone in Personality and Behavior
Testosterone affects the entire body and all the organs in it. This is why the brain is also affected by it and as a result, testosterone also affects behavior. It has been seen that testosterone can affect career choices, financial decisions and associated risk taking. In a study in 2009, it has also been found that testosterone can account for selfishness in men. It can also regulate fight-or-flight response. However, testosterone does not affect the mood of an individual.
It has also been found that testosterone accounts for aggressiveness in human beings. In fact, it has been seen that castrated men are less aggressive. Aggressiveness is the reason behind many crimes, so it can also be said that testosterone is also responsible for criminal behavior. It has in fact been seen that criminal intent rises in boys during puberty – the same time when their testosterone levels increase. Medical studies have also found a link between criminal activities and testosterone.
Effects of Testosterone on Health
Testosterone can create many beneficial effects in men. It can maintain cardiovascular health, reduce the chances of heart attack, obesity, and high blood pressure. However, if not kept in check, testosterone can also cause men to be injured easily, consume more alcohol, smoke more and contract sexually transmitted diseases. Testosterone does not have harmful effects on prostate cancer, but if the individual has undergone testosterone deprivation therapy, then the increase of testosterone levels in such an individual can be the reason for the rapid spread of an existing prostate cancer.
Low levels of testosterone can cause low libido, decreased bone mass and strength; it can also cause testicular dysfunction and hypothalamic-pituitary dysfunction. Low levels of testosterone have also been associated with the development of Alzheimer’s disease. People with low testosterone levels and androgen deficiency can be treated with hormone replacement therapy. Testosterone therapy can also improve the management of type 2 diabetes.
However, if improper testosterone supplementation is done, it can produce some side effects like acne and hair loss. More serious side effects include an abnormal increase of red blood cells (hematocrit) – a condition which is also called polycythemia, infertility and worsening of sleep apnea – a condition where the individual cannot breathe properly while sleeping. Polycythemia increases the risk of heart disease in turn. Exogenous administration of testosterone also involves the risk of impairing the testes and endogenous sperm production.
A testosterone supplementation should always be done on proper medical advice. While a supplementation can do a lot of good in case of testosterone decrease due to medical conditions, treating the decline of testosterone due to normal aging is not advised. Also, people who have undergone or are undergoing treatment for breast cancer or prostate cancer should never opt for a testosterone supplementation therapy.
Causes of Low Testosterone
Low level of testosterone in the body is called hypogonadism, and can be on three levels – primary (when the problem is in the Leydig cells or the testes), secondary (when the problem is in the pituitary gland) and tertiary (when the problem is at the level of the hypothalamus). Old age is definitely the biggest cause of primary hypogonadism – as discussed in detail in the next section. However, there are other factors as well, which can induce primary hypogonadism in a man – injury or infection in the testicles among them. Other minor reasons that can cause low testosterone include obesity, stress and alcoholism.
The more serious reasons that can induce a decrease in low testosterone can be some chronic illness like liver cirrhosis or kidney failure, excess of iron in blood (hemochromatosis), genetic abnormalities, pituitary dysfunction, inflammatory diseases, cancer treatment like radiation or chemotherapy, medications like corticosteroids or hormones used in the treatment of prostate cancer.
Testosterone Levels and Age
During puberty, the testosterone levels increase in males. This increase continues till early adulthood, and accounts for the high levels of testosterone during this period. After a man reaches 30 years of age, testosterone levels start declining at the rate of 1% per year. If the levels of testosterone fall too low in an older man, it becomes important to know whether this was due to his old age, or due to some disease like hypogonadism. Though low levels of testosterone are not the only reason for all the symptoms and signs of aging, there are a few symptoms that low testosterone levels can trigger.
For example, altered sexual functions can be seen with low testosterone levels. Men may experience less number of spontaneous erections, decrease in sexual desire, and even infertility. There can also be insomnia or sleep disturbances associated with low levels of testosterone. Men may also experience low energy low energy levels and hot flashes due to a decrease in testosterone.
Physical and emotional changes are also possible due to low testosterone levels. Common physical changes include reduced muscle mass and bone density, increased fat in the body and loss of hair. Gynecomastia (enlarged breasts) or breast tenderness are also possible. Common emotional changes include reduced self-confidence and motivation, depression, lack of concentration and reduced memory.
Testosterone can be increased naturally in the body through various environmental factors. The fat cells in the body produce aromatase. This enzyme has a prime role in breaking down testosterone into estrogen and estradiol. If an individual loses weight, the amount of fat cells reduces. This causes aromatase to be produced in less amounts. This may increase the amount of testosterone present in the body.
Vitamin D, if present in the levels of 10-25 mcg/d, can also increase the levels of active testosterone in the body. Zinc has to be present in adequate amounts in the body, otherwise testosterone levels might fall. However, supplementations of zinc above a certain level cannot help produce extra testosterone. Other environmental factors that temporarily increase testosterone levels in the blood include REM sleep (where the night time levels of testosterone increase), resistance training, and dominance challenges.
Testosterone in Sports
Testosterone has always been known to improve performance, and this is why athletes sometimes take testosterone supplements in order to perform better in their field. It can improve strength and endurance. It can be administered through various ways like subcutaneous injections, implantable pellets, transdermal patches and gels.
However, exogenous supplementation of testosterone can cause lower endogenous production through the Farquharson phenomenon. This is one of the reasons why it is one of the top items in the banned items list of the WADA (World Anti-Doping Agency). But the most important reason why it is banned is because it is considered to be “unfair means” for increasing performance, and winning in sports. This means that it is considered “cheating” the other athletes who are not using any performance enhancers.
That does not stop the athletes from using it in sports, though. In the year 2010, 60% of all the athletes, who were found to have used illegal substances for sports, had high levels of testosterone in their blood or urine samples. Athletes believe that testosterone can not only increase their performance and endurance, but also speed up recovery times and increase their combativeness and sex drive. However, the effect of testosterone in the body is a controversial topic.
While athletes and some researchers believe that testosterone produces a mass improvement in performance and endurance, others believe that it cannot produce overnight effects. It cannot give a jolt of energy to sportspersons in order to improve their performance, since testosterone acts over time to build muscle and strength in the athlete. But even then, there has to be a considerable amount of effort (in terms of exercise) on the part of the athlete. Simply taking testosterone without any exercise or a suitable diet will only do more harm than good.
American bodybuilders first started using testosterone to improve their performance in the 1950s, when they suspected the Russian weightlifters to be using them. The Russian weightlifters were all winning gold medals, and hence the suspicion. However, nothing conclusive was proven till the 1990s, when Dr. Shalender Bhasin (professor of endocrinology at the Boston Medical Center) published his study on testosterone in the New England Journal of Medicine.
In this study, Bhasin tried to use testosterone in a disease (like AIDS) which necessarily wears out muscle mass. Those who were administered with the hormone had larger biceps and triceps, and were stronger during exercises like bench presses. However, increased muscle and strength does not always mean that you will perform better in sports. For example, a person who runs marathons may find that the muscle mass is exerting more weight on their joints than what they can hold. This can bring about injuries.
Pure testosterone cannot survive for very long in the body, because of aromatization through various enzymes. Besides, the administration of pure testosterone is also very uncomfortable for athletes. But because of its extensive use in sports, testosterone is generally esterified, and then sold commercially. Esterification not only increases the life of testosterone in the body, but also increases it oil solubility, which makes its administration easier.
As a simplified rule, it can be said that an increase in the number of carbon atoms increases the solubility of the ester in oils. For this reason, a testosterone ester that has 8 carbon atoms will have more oil solubility than an ester that has only 3 carbon atoms. However, structural factors also influence the solubility of an ester.
It should also be noted that if testosterone is administered in its pure form, it enters the blood immediately and is used up very quickly. However, if testosterone is esterified and then administered, then it stays in the muscle and is slowly picked up by the blood and used accordingly. This happens due to a factor called partition coefficient. Whether an ester is slow-acting or fast-acting depends on this factor. Pure testosterone has a low coefficient of partition, which lets it enter the bloodstream quickly. On the other hand, esterified testosterone has a high coefficient of partition, and is able to remain in the body for longer.
Slow-acting or high partition esters are generally more oil soluble, whereas fast-acting or low partition esters are less oil soluble. Slow acting esters are generally preferred by athletes as they stay in the body for a longer time –reducing the need for frequent injections. It also helps keep the levels of testosterone quite steady in the bloodstream.
Types of Available Testosterone Esters
There are some common types of testosterone esters available, which are generally administered through injections. They are discussed as below:
Methods of Administering Testosterone
Testosterone can be administered into the body in a number of ways, the most effective of them being the injections. The various methods are discussed as below.
Transdermal patches generally have testosterone suspended in a gel which has an alcohol base. Some chemical enhancers would have been added to the gel in order to make it enter the skin more easily. Sometimes these enhancers may cause irritation in the skin. Transdermal patches are available in two brands in the US – Testoderm and Androderm.
Transdermal gels or creams are supposed to be applied directly to the skin. The creams are generally based on safflower oil, whereas gels are alcohol based. These are faster acting than the patches and may need to be applied twice daily. The brands in which transdermal gels are available are Testim and Androgel.
Subcutaneous pellets are generally used for only medical purposes. Small crystalline pellets of testosterone (usually of 200 mg) are inserted under the skin. The pellets then keep supplying the body with about 3 mg of testosterone every day. The pellets need to be replaced every 3 to 4 months.
Importance of Testosterone in a Cycle
If an athlete is using a steroid cycle, then testosterone should definitely be included in it. Ideally, it should be the primary compound that the athlete is using, but in the very least it should be used as a supportive compound. Primary compound is something that is the main contributor to acquiring muscle mass, and must be administered in the appropriate dosage of bodybuilding.
Including testosterone in every cycle is important because it is a steroid that is originally produced by the human body, and is required for a lot of bodily functions. It is also the safest among all steroids. When supplied externally with a hormone that the body produces by itself, it gives the body an extra boost to produce muscles and physical strength.
It is also a rule of taking steroids for sports use that testosterone should be the only steroid used in the first ever cycle of any athlete. This is not only because it is safer to introduce as a steroid, it is also a fact that the body will react less to a chemical that it has been producing already. This also helps us to judge the way an athlete’s body reacts to steroids. If his body reacts adversely to testosterone, then the reactions might be even severe in case of other steroids. This is why, for a first cycle, it is dangerous to stack many steroids, because then if there are any adverse reactions, the cause of the reactions cannot be traced.
Excluding testosterone from a cycle can also be a bad idea. Steroid intake inhibits the natural testosterone production of the body. As such, if testosterone is left out from a cycle, the body will be completely devoid of testosterone during the cycle. Since testosterone is required for many of the bodily functions to continue normally, it may cause a lot of adverse effects on the body. The importance of including testosterone in every cycle cannot be stressed enough, and anyone who leaves out testosterone from their cycles is putting their body in great danger.
How to Incorporate Testosterone in a Cycle
Using testosterone responsibly can yield amazing results. A first time user can expect a muscle gain of 30 to 50 pounds in 3 months. Out of this, 10 to 15 pounds may be water weight and may be lost once the testosterone administration has stopped. However, the muscle mass that was gained from the cycle will not be lost. Testosterone also helps in losing fat, but it mainly helps in gaining muscle.
When starting a testosterone cycle, an athlete must assess his goals as a first step. Then he should decide the type of testosterone that will help him achieve his goals. A rule about using steroids is that faster acting steroids create more side-effects, since they are released into the body too quickly. They will also be degenerated faster into harmful compounds like DHT and estrogen. Also, a very slow acting testosterone ester may be hard to control. So the athlete needs to strike a balance between the two to choose the best ester for himself. After choosing the form of testosterone, the athlete also needs to choose a proper brand of the ester so that his body does not face a lot of harm instead of good.
The cycle should start with a 500 mg/week dosage of testosterone for a beginner. This should continue for the first 10 weeks. For the 11th week, the dosage should be 300 mg, and for the 12th and last week, the dosage should be reduced to 200 mg. Following the 12th week, the athlete is advised to take 100 mg of clomid per day and 0.25 mg of arimidex every alternate day for a week. This is to prepare the body so that it can get out of the testosterone cycle. On the 14th week, it is advised to take 0.25 mg of arimidex after every 2 days, and 50 mg clomid each day for a week.
Along with the medication, diet and exercise should also be taken care of, in order to reap the full benefits of the testosterone cycle. First of all, the athlete should start taking 2000 calories more than what he usually does. This will ensure that the muscle building goes as it is expected to. Also, the protein intake should be increased to around 2 grams for every pound of muscle weight of the athlete.
The athlete’s training program should remain more or less the same. If required, it can be increased by 2 sets per body part per week. Also, an athlete should get a minimum of 8 hours of sleep every night.
Using an anti-aromatase will ensure less water gain. Otherwise, when the athlete comes off this cycle, he will lose the water weight that was gained. However, this is nothing to be alarmed of, since the muscle weight will be retained. Water weight approximately makes up for 10% of the total weight gained during a testosterone cycle, if no anti-aromatase is used. This is all the water that the athlete will lose when off the cycle.
Detection of Testosterone Doping in Sports
Mostly testosterone can be detected through a urine test. In this test various hormone ratios are tested. The testosterone to epitestosterone, which should normally be below 6, the testosterone to luteinizing hormone ratio and the carbon 13 to carbon 12 ratio are tested in order to detect exogenous testosterone in the body of the athlete. For some test procedures, the athlete’s own previous results may be used for reference.
Testosterone can also be detected through blood tests. In these tests, blood is drawn in the morning between 7 am and 10 am. It can be repeated in order to check the accuracy of the tests. The normal testosterone levels for men in this test are 300 ng/dL to1000 ng/dL, and that for women is 15 ng/dL to 70 ng/dL.
Some Myths about Testosterone
Like all other drugs, testosterone has some mystery around it for the people who do not use it. This leads to all sorts of myths around it. Here are some such myths and the reality about them.
Side Effects of Testosterone
Though the hormone itself is not harmful, the commercial drugs that contain it may have adverse side effects on the body. Some of the minor side effects of testosterone that do not require medical attention can be blurry vision, sudden blindness, slurry speech, sudden failure of speech, headache, seizures, mouth or gum irritation, and sudden weakness in certain parts of the body. Some of these side effects may be eliminated by adjusting the dosage or brand of drugs that is being used. Other, more severe side effects include the following:
If used by athletes who are yet to reach puberty, it may cause virilization. The genitalia may develop beyond what is appropriate for the age, and similar developments may occur in bones. Sometimes, when the testosterone administration is stopped, the bones and genitalia return to the normal sizes, but this may not occur always.
As soon as any of these symptoms are observed, medical help should be sought on emergency. There are several ways in which to alleviate the symptoms of overdose or side effects, which an experienced medical practitioner may be able to administer.
Prevention and Reversal of the Side Effects of Testosterone
Basically, most of the side effects of testosterone occur due to the compounds that form when testosterone breaks down. Once testosterone hits the system, it can take two paths, and produce side effects. The first is where 5-α reductase degenerates testosterone into dihydrotestosterone or DHT. DHT is even more androgenic than testosterone.
The second path is where testosterone gets aromatized into estrogen. Minimizing these conversions can ensure less number of side effects. For example, acne is caused by high levels of cortisol, and it can be prevented by stopping the oil from forming internally. This can be done by taking Vitamin A and Vitamin B5 supplements. Bathing twice daily may also help. In the winter, it is also advised to mix 2 cups Epson Salt along with half a cup or a full cup of chlorine bleach to the bath water.
Erectile dysfunction, gynecomastia, water retention and bloating are caused by excess of estrogen. Estrogen can be stopped from forming by using supplements that contain the elements molybdenum, magnesium, selenium and zinc. Vitamin A, Vitamin B6 and Vitamin C supplements may also help. If estrogen has formed, it can be got rid of by using anti-aromatase compounds like arimidex.
Baldness is caused by the DHT. It attaches itself to the hair follicles in the scalp and creates an inflammation that deprives the hair of oxygen. This starvation makes the hair die and fall out. Propecia or finastride drugs stop testosterone from degenerating into DHT, and may help prevent hair fall. Using shampoos like Nizoral, which block the effect of DHT in the scalp, can also help.
When the testicles have already shrunk due to prolonged use of testosterone, this physical change can be reversed by administering HCG or Human Chorionic Gonadotropin hormone. Clomid is a medication that contains HCG and can be administered. It will act like LH and stimulate the body to produce more testosterone. Also, HCG has no observable side effects.
Another serious, but preventable side effect of testosterone use is the increase in cholesterol levels in an individual. It can be avoided by following a cholesterol conscious diet pattern while on a testosterone cycle. It is also necessary to keep getting blood tests done regularly, since abnormal levels of cholesterol increase the risk of heart attack. Testosterone does not affect the cholesterol levels of every individual, so a blood test also helps an athlete know if it is affecting his cholesterol levels or not.
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