Testosterone is a steroid hormone from the androgen group. It is present in both men and women as well as in other vertebrates. Testosterone is responsible for physical changes in men during puberty, including deepening of the voice, growth of the penis, testes, muscles, facial, pubic and body hair, getting taller, and the production of sperm to be able to have children. In addition, testosterone plays a great role in fat distribution, red blood cell production and maintaining bone density.
In women, testosterone is present in smaller amounts. It functions to maintain sex drive, keep bones healthy, manage pain levels, and preserve cognitive health.Also, it gives women a sense of motivation, assertiveness, and a feeling of well-being.
In men, the brain and pituitary gland (small gland at the base of the brain) control testosterone production by the testes. From there, it moves through the blood to do its work. In women, testosterone is produced in various locations. One quarter of testosterone is produced in the ovaries, a quarter is produced in the adrenal glands, and one half is produced in the peripheral tissues from the various precursors in the ovaries and adrenal glands.
The levels of testosterone change from hour to hour and vary from person to person. They tend to be highest in the morning (that’s why early morning erections are common) and lowest at night. In general, the normal testosterone levels in males ranges from 270 to 1,070 ng/dL. From the age of 30 onward, total testosterone levels in men decrease by 1% per year.
The production rate of testosterone in normal female is 0.2 to 0.3 mg/day. Normal blood testosterone levels in females can range from 30 to 95 nanograms per deciliter (ng/dL). The testosterone level in women is highest around age 20 and slowly declines until it is half as high in their 40s. For those who had their ovaries removed, testosterone production significantly drops by half, sometimes resulting in less than the normal blood testosterone levels.
The promise of testosterone therapy in both men and women may seem enticing, but there are a lot of misconceptions about what the treatment can and can’t do. Millions of American men rely on testosterone therapy to restore normal levels of the hormone and to help them feel more alert, young, energetic, sexually functional, mentally sharp, and feel good about themselves. However, legitimate safety concerns linger. For those who want to undergo testosterone replacement therapy, it is recommended to consult with a qualified and experienced physician first for further medical assessment and evaluation.
Testosterone levels generally peak during the adolescent period and early adulthood. As men age and when they reach andropause or sometimes called male menopause (usually between the ages of 40 and 80), they can experience a number of symptoms related to natural decline in testosterone levels.
One of the most common symptoms is a decrease in sexual function. They experience reduced sex drive, fewer erections, hot flashes, and infertility. Other physical changes related to low testosterone levels include increased body fat, decreased muscle mass and body hair, fragile bones, swelling or tenderness in the breast tissue, increased fatigue, and disordered cholesterol metabolism.
Despite the fact that low testosterone can cause decreased energy levels, it can also cause insomnia and changes in sleep patterns. The affected individual can also experience emotional changes such as feelings of sadness or depression, low self-esteem and motivation, lack of concentration or focus, and an overall decreased in sense of well-being. While each of these symptoms is related to low testosterone, they may also be related to other medical conditions such as thyroid problems, autoimmune disorders, side effects of medications and mental problems. Testosterone replacement therapy can help improve the signs and symptoms of low testosterone in men. Depending on the nature and severity of testosterone deficiency, doctors may prescribe testosterone in the form of injections, pellets, tablets, patches, or gels.
Hypogonadism or testosterone deficiency is a condition in which the body does not produce sufficient levels of testosterone as a result of an underlying medical condition or other causes. It is likely that testosterone deficiency is under-diagnosed and is often mistaken for other medical conditions as its signs and symptoms resemble other diseases especially psychiatric disorders. Testosterone deficiency is classified according to the location of its cause:
Hypogonadism may be present at birth (congenital) or may develop later in life (acquired). Congenital causes of hypogonadism include the following:
Acquired causes of testosterone deficiency include the following:
Testosterone replacement in women
In women, testosterone may have a direct effect on libido and sexual response. However, there is no solid link between high testosterone level and high sex drive nor low testosterone and low sex drive. Women can have low testosterone levels and have a normal sex drive or have high testosterone levels and little sexual desire. Sex drive in women may vary and is not affected by testosterone alone.
Research shows that testosterone replacement therapy for women does impact the sex drive and may help reduce symptoms associated with sexual dysfunction in women. But the long-term safety of testosterone supplementation for women is still unclear. For this reason, prescription of testosterone for women might be appropriate if:
Increased longevity and population aging will increase your risk of developing late onset hypogonadism. It is a common condition, but is often mistaken for other medical conditions, making it frequently underdiagnosed and undertreated. The start of testosterone replacement therapy (TRT) requires the presence of below the normal testosterone levels, along with signs and symptoms of hypogonadism.
Although controversy remains regarding its use for the elderly due to lack of large-scale, long-term studies investigating its benefits and risks, reports indicate that TRT may produce a wide array of benefits for those with testosterone deficiency, including improvements in sexual desire and function, muscle mass, bone density, body composition, cognition, mood, erythropoiesis (red blood cell production), quality of life, and cardiovascular disease.
Low testosterone can alter a person’s mood. Researchers first noticed the effects of low testosterone in animals. Since then, they have studied this effect in different kinds of mammals. The researchers observed that males with decreased testosterone become much more aggressive and prone to fighting instead of becoming docile and quiet. Generally, questionnaires are used to monitor psychological factors, such as positive mood responses and negative mood responses. Other studies have assessed similar attributes such as being angry, alert, energetic, irritable, tired, sad, nervous, and changes in well-being. However, changes in mood parameters such as having low mood are generally experienced by hypogonadal men.
Testosterone replacement may have an antidepressant effect in individuals suffering from depression. To prove this, Zarrouf et al conducted both a systematic review of the literature and a meta-analysis that explores the effect of testosterone administration on depression. The results of the meta-analysis of the data from seven studies showed a significant positive effect of testosterone therapy on Hamilton Rating Scale for Depression (HAM-D) response in depressed patients when compared with placebo. A related study by Pope et al also showed improvement in scores on the Hamilton Depression Rating Scale in men who had refractory depression and low or borderline testosterone levels who received transdermal testosterone gel supplementation for 8 weeks than subjects receiving placebo.
Testosterone replacement therapy is considered as an effective treatment for depression related to low testosterone levels. Its efficacy is roughly equivalent to antidepressants such as selective serotonin reuptake inhibitor (SSRI) in minimizing the symptoms of depression. In one study, Seidman et al reported that 400 mg testosterone replacement biweekly for 8 weeks in five depressed men who had low testosterone levels and had not responded to SSRI showed improvements in depressive symptoms.
Over the years, researchers have uncovered a significant connection between low testosterone and diabetes. In fact, men with type 2 diabetes are twice as likely to have low testosterone levels compared to men who don’t have diabetes. Low levels of testosterone in men are associated with insulin resistance or reduced insulin sensitivity. Insulin resistance is a medical condition wherein your body produces insulin but does not use it properly. This in turn leads to high blood glucose levels. Over time, insulin resistance can lead to type 2 diabetes and other health problems.
In one study, Kapoor et al investigated the effect of testosterone treatment on insulin resistance and glycemic control (blood sugar levels) in 24 hypogonadal men aged 30 and above with type 2 diabetes. The researchers found that testosterone replacement therapy (TRT) reduces insulin resistance and improves blood sugar levels in all participants. A similar study involving 48 middle-aged men (24 subjects received testosterone for 3 months and 24 did not) with type 2 diabetes and symptoms of testosterone deficiency showed that oral testosterone treatment improves blood sugar levels, decreases visceral obesity, and improves symptoms of testosterone deficiency including erectile dysfunction. In all of the participants, the benefit of oral testosterone supplementation therapy exceeds the correction of symptoms of testosterone deficiency.
As testosterone declines with age, so does cognitive function. Treating older men with testosterone may help improve spatial intelligence (deals with judgment and the ability to visualize) and verbal memory, according to a small study conducted by researchers at the University of Washington in Seattle.
In another study, Cherrier et al investigated the effects of 6-week testosterone supplementation via injection among 19 men aged 63 to 85 years with Alzheimer disease (AD) or mild cognitive impairment (MCI). Improvements in spatial memory, constructional abilities and verbal memory were evident and their levels of testosterone was raised by an average of 295%. In a related study by Ackermann et al, healthy subjects encoded pictures taken from the International Affective Picture System (IAPS) and they underwent a free recall test 10 minutes after memory encoding. The study revealed that higher levels of testosterone were related to increased brain activation and that testosterone has a male-specific role in enhancing memory by increasing the biological salience of incoming information.
As men age, their testosterone concentrations in the blood start to decline, as do their bone densities. When the level of bone density falls below the normal, osteoporosis can occur. The main characteristic of osteoporosis is reduction in bone density and quality, making affected individuals susceptible to fractures or bone breaks. There is a high incidence of early bone loss and low bone density (osteopenia) in men with low levels of testosterone which increases their risk for osteoporosis. And the longer the duration of testosterone deficiency, the greater the risk.
Sex steroids in both sexes play a pivotal role in the maintenance of bone quality. Because bone density is also low in hypogonadal men, testosterone replacement therapy would help increase their bone densities. In one study investigating the effect of testosterone treatment on bone mineral density in men over 65 years of age, Snyder et al reported that testosterone patch did increase bone mineral density of the lumbar spine as well as serum testosterone concentrations after 36 months of treatment. In a similar study, Amory et al investigated the effects of testosterone therapy and finasteride, a 5 alpha-reductase inhibitor (prevents conversion of testosterone ) among 70 men aged 65 years and older with low testosterone levels for over 36 months. The study showed that the combination of testosterone therapy and finasteride increases vertebral and hip bone mineral density (BMD).
When a person suffers from loss of muscle and fat tissue due to chronic illness, this condition is called cachexia. The general loss of weight and muscle mass that naturally occurs with advancing age is called sarcopenia. The term “catabolic wasting” encompasses both of these medical conditions.
Testosterone plays a critical role in muscle building and maintaining muscle mass, and many muscle-wasted patients are deficient in testosterone. One study reported that testosterone levels was deficient in over 70% of men with cancer cachexia. The researchers observed that total testosterone levels were lower in cancer patients with cachexia compared to cancer patients without cachexia. A number of studies have reported that testosterone replacement therapy has been useful in promoting lean weight gain for patients with HIV/AIDS- or COPD-related cachexia.
The oral testosterone derivative oxandrolone has been used for several years as a therapeutic intervention against unintentional weight loss associated with HIV/AIDS-related muscle wasting. In a double-blind, randomized study, oxandrolone at doses of either 5 mg or 15 mg daily was effective in improving body weight and well-being in 63 HIV-positive men with weight loss of more than 10% of initial body weight.
Most HIV-infected men with decreased testosterone levels have testosterone deficiency. Treatment of hypogonadal HIV-infected men with testosterone supplementation can lead to increased muscle mass and improvements in quality of life, and improvements in depression. In women, testosterone treatment has shown increase in weight and social functioning.
In one study involving seventy-four HIV-infected patients who received bi-weekly testosterone injections followed by 12 weeks of open-label maintenance treatment for a period of 6 weeks, the results showed improvement in symptoms of clinical hypogonadism, thus restoring sex drive and energy, alleviating depression, and increasing muscle mass. In another study, Coodley et al reported that 200 mg of testosterone cypionate injections every 2 weeks for 3 months in HIV-infected patients did appear to produce an improved overall sense of well-being and muscle strength. The same researchers also investigated the effects of a steroid hormone called dehydroepiandrosterone (DHEA) in treating persistent depression in patients with HIV/AIDS. DHEA appears to be a useful treatment in reducing symptoms of non-major depression in HIV-infected patients.
Erections are clearly androgen-dependent. Testosterone has always been assumed to play a major role in erectile dysfunction (ED) because of the following reasons:
In one study assessing the benefits of testosterone for ED, Kalinchenko et al reported that combining oral testosterone undecanoate with anti-diabetic drugs in diabetic patients who do not respond to Viagra therapy, has been observed to restore sexual function. In a double-blind placebo controlled, cross-over study, Schiavi et al treated healthy men with erectile dysfunction with biweekly injections of 200 mg of testosterone enanthate for over a period of 6 weeks separated by a washout period of 4 weeks. Results suggest that androgen administration among the subjects was able to increase ejaculatory frequency, reported sexual desire, masturbation, sexual experiences with partner, and sleep erections.
Testosterone can be used to improve one’s performance. In sports, testosterone shots or creams are often promotes as magic bullets that spur athletes to run, jump, swim and to recover faster, and to become more aggressive and focused. However, it is considered to be a form of doping in most sports. Testosterone hormone supplements stimulate the endocrine system to adjust its production and lower the natural production of testosterone, so when it is discontinued, the natural production of the hormone is lower than before. Anabolic steroids (including testosterone) have also been taken to build muscles, enhance strength, or endurance. They work directly by increasing the protein synthesis of the muscles leading to large muscle fibers and enhanced repairing ability.
After a series of scandals and publicity, such as Ben Johnson’s improved performance at the 1988 Summer Olympics, the use of anabolic steroids was banned by many sports organizations. In 1990, the United States Congress prohibited testosterone and other anabolic steroids, which were designated as controlled substances, resulting in the creation of the Anabolic Steroid Control Act.
Some female athletes may have naturally higher levels of the hormone testosterone than others, and may be asked by certain sports regulating bodies to consent to a “therapeutic proposal,” either surgery or drugs, to decrease testosterone levels to an acceptable level to compete fairly.
There is a significant difference between testosterone boosters and steroids. Testosterone boosters consist of natural ingredients and supplements such as those from plants, while steroids are synthetic substances that are created in a laboratory and are usually prescribed by doctors to treat a variety of health related issues. However, the use of steroids for the purpose of muscle building or enhancing an athlete’s performance without a prescription is illegal. There are two common steroids in the market: anabolic and androgenic steroids. Anabolic steroids are designed to promote muscle growth, while androgenic steroids are designed to assist with sexual dysfunction such as decreased libido and erectile dysfunction. Most anabolic steroids are taken orally, through a pill, while others are injected.
Anabolic steroids did not receive a worldwide recognition until the 20th century, but the use of pure testosterone can be traced back to the original Olympic Games. Early Olympic athletes were known to ingest animal testicles before a competition to improve their performance. In 1935, researchers in the Netherlands were the first to isolate a few pure milligrams of testosterone. They named the substance “testosterone” from the words testicle, sterol, and the suffix of ketone. Also during this year, Butenandt and Hanisch created the first synthetic version of testosterone from cholesterol. It was made available to the medical community for experimentation and treatment purposes. Later, during World War II, it was found that this artificial form of testosterone helped malnourished soldiers gain weight and improved performance during combat.
After the war, athletes began to use steroids to have an edge over other competitors. In the 1956 Olympics in Moscow, Soviet wrestlers performed at exceptionally high levels after using the male anabolic steroid testosterone. After learning about this incident, an American physician named John Bosley Ziegler created a more selective form of what we know as anabolic steroids. From that point until the early 1970s, the use of anabolic steroids became increasingly popular among Olympic athletes and professional sports players. In 1975, the International Olympic Committee finally prohibited the use of steroids and other performance-enhancing drugs in Olympic competition. However, black market sales continued to increase in the following years.
In 1988, the Anti-Drug Abuse Act was introduced in order to stiffen the penalties for the sale and possession of anabolic steroids. In 1990, the United States Congress prohibited anabolic steroids and other performance-enhancing drugs and placed certain anabolic steroids on Schedule III of the Controlled Substances Act (CSA). Previously, the use of steroids was controlled only by state laws. Today, illegal sales of steroids are still prevalent among athletes, bodybuilders, and even adolescents.
There is a wide array of mild to serious side effects associated with abuse of anabolic steroids. The use of steroids in the long run can alter normal hormonal production in the body. The user generally experiences an increase in muscle mass and strength very quickly. They experience heightened ability to lift heavier weights and train for more often and for longer periods of time because of their improved recovery rate. However, the user can experience fluid retention, causing the muscle tissue to look soft and bloated. Side effects of steroid use vary depending on the user’s gender. Men may experience shrinkage of the penis and testicles, reduced sperm count, prostate problems, impotence, gynaecomastia (breast development), and baldness. For women, steroid use can cause amenorrhea (loss of the menstrual cycle), facial and body hair, shrunken breasts, deepened voice, and abnormal growth of the clitoris.
Users of anabolic steroids can display drug-seeking behavior as a result of physical and psychological drug dependency. Physical withdrawal can lead to mood swings, fatigue, loss of appetite, restlessness, sleep deprivation, reduced sex drive, steroid cravings, and in worst cases, depression that can lead to suicide.Management for severe anabolic steroid addiction focuses on supportive treatments and medication intervention. However, most side effects can be reversed if steroid use is stopped.
Most of the studies done on the negative side effects of testosterone are anecdotal and based on case reports—no large retrospective or prospective studies investigating its adverse effects and risks have been conducted. Some of the known adverse effects of testosterone use include the following:
The Food and Drug Administration (FDA) has required pharmaceutical companies to include warning information about the possibility of adverse effects such as increased risk of heart attacks and strokes in testosterone products.
Today, androgen deprivation or suppression therapy remains a cornerstone of treatment for men with advanced cancer of the prostate, so it’s no surprise that testosterone replacement therapy is contraindicated for those diagnosed with the disease. The traditional view was that testosterone fuels growth of cancer cells in the prostate and high levels of testosterone can possibly contribute to its spread. Experts thought that cutting off the fuel supply—by administering androgen deprivation therapy to reduce testosterone levels—was an effective treatment.
In the past few years, some research has challenged many of these beliefs. Recently, there has been a paradigm shift whereby testosterone replacement therapy administration in prostate cancer patients has increased despite its supposed risk. Many longitudinal studies focusing on the relationship of endogenous testosterone levels and subsequent risk of prostate cancer failed to find any association.
In a large meta-analysis of 18 prospective studies involving 3,886 men, there was no association between the risk of prostate cancer development and serum concentrations of testosterone. Morgentaler et al proposed a saturation theory that explains why testosterone does not directly cause prostate cancer. According to his model, prostate cancer cells require a certain amount of testosterone in order to grow and multiply, and there is a limit to the ability of androgens to stimulate growth of prostate cancer cells. That is why drastically reducing the levels of testosterone through hormone therapy can keep existing prostate cancer cells from growing. Normal prostate cells and even cancer cells seem to have a saturation point and are not affected as testosterone levels increase.
In the latest meta-analysis presented in the American Urological Association 2015 Annual Meeting, Dr. Peter Boyle reported that testosterone, whether occurring naturally or taken as replacement therapy, does not cause prostate cancer or stimulate increases in the levels of prostate-specific antigen (PSA) in men.However, even with the newest advances in testosterone research, most primary care physicians and various specialists continue to be hesitant about prescribing testosterone.
Cardiovascular diseases are associated with insufficient level of the sex hormone testosterone. In the largest study to date, Khaw et al investigated the effects of testosterone levels and mortality among 11,606 healthy men aged 40 to 79 years old over a 6- to 10-year follow-up period and observed a significant association between low levels of testosterone and increased risk of cardiovascular diseases.
In the most recent study, Dr. Barua, an assistant professor of medicine at the University of Kansas School of Medicine, and his colleagues reported that testosterone supplementation can reduce the risk of myocardial infarction (MI), stroke, and all-cause mortality at normal levels. In hopes of providing some answers to testosterone and cardiac disease association, the study team retrospectively examined national data on 83,010 men (aged 50 and above) with documented low testosterone who received care from the Veteran’s Administration between 1999 and 2014. The results of the study showed that treated men with testosterone levels at normal range were 56% less likely to die during the follow-up period, 24% less likely to suffer a myocardial infarction, and 36% less likely to have a stroke.
Symptoms associated with low testosterone level may resemble other medical conditions such as thyroid problems, hormonal imbalance, side effects of medications and illegal drugs, and mental problems. To determine what’s causing these symptoms, it is recommended to schedule an appointment with your doctor for a blood test. Test to determine testosterone levels should be done in the morning between 7:00 and 10:00 am. For normal results, the test should be repeated to make sure that the result is accurate. In healthy men, the levels of testosterone can change a lot from day to day, so a second test is required.
After the decision to restore testosterone levels has been made, the next step is deciding on the most effective route of administration. There are several different modes in which testosterone can be delivered, but the best method varies from person to person. A number of factors should be considered when selecting a specific testosterone modality for replacement therapy. These factors include the following:
A testosterone test, also called serum testosterone test, measures the amount of testosterone in the blood. This test is ordered to determine if a person has low levels of testosterone. It is important to inform your doctor about your current medications as it may affect the result of the test. Medications that can alter testosterone test results are steroids, anticonvulsants, barbiturates, clomiphene, and estrogen therapy.
The levels of testosterone in the blood can be measured in terms of total, bio-available, or free testosterone and there are various tests which can be used to measure each type of testosterone:
The different methods of testosterone delivery are the following:
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